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Lung Transplantation

Heart/Lung and Lung Transplantation

1. History

A. Alexis Carrel- 1907
B. Demikhov- 1940s
C. Lower/ Shumway- 1960s
D. Clinical heart/lung transplantation
1) Cooley- 1968
2) Lillehei- 1969
3) Barnhard- 1971
4) Modern- era- Reitz
E. 1963- first human lung transplant
F. 1983- Cooper- first successful lung transplant
G. 1985- Cooper / Patterson- double lung transplant

2. Donor Selection

A. Age <60 years
B. No history of pulmonary disease
C. Smoking history < 20 packs/ year
D. Normal chest x-ray
E. Adequate gas exchange
F. Normal bronchoscopy
G. Acceptable sputum gram stain
H. Normal serology
I. ABO compatibility
J. Adequate size matching

3. Absolute Donor Criteria

A. Adequate gas exchange
1) PO2 >300 on FiO2 1.0
2) PO2 >100 on FiO2 0.4
B. Absense of significant infiltrates
C. Normal serology
D. ABO compatibility

4. Indications of Thoracic Transplantation

A. Single lung transplant
1) Pulmonary fibrosis
2) Emphysema
B. Primary pulmonary hypertension
C. Double lung transplants
1) Septic lung disease
2) Cystic fibrosis
3) Bronchiectasis
D. Emphysema
1) Primary pulmonary hypertension
E. Heart / Lung transplant
1) Irreversible disease of both heart and lung

5. Recipient Selection

A. Age <65
B. Other disease processes
C. Previous surgery
D. Steroids
E. Smoking
F. Nutrition
G. Ventilator dependence
H. Timing of transplant
I. Psychosocial factors

6. Lung Preservation for Transplantation

A. Hypothermia
B. Lung inflation
C. Pulmonary artery vasodilation- PGE1
D. Pulmonary artery flush- solutions include:
1) Modified eurocollins solution
2) Belzer's (Wisconsin) solution
3) Low potassium Dextran
E. Low potassium, colloids, free radical scavengers

7. Early Complications of Lung Transplantation

A. Reperfusion pulmonary edema
B. Primary graft failure
C. Hemorrhage
D. Bronchial dehiscence
E. Non-infectious pleural space problems

8. Infection in Lung Transplantation

A. Transplanted organ exposed to external environment
B. Target organ for CMV
C. Bacterial, viral (CMV), fungal Protozoan (PCP)
D. Infection increases expression of
1) HLA antigens
2) Adhesion molecules (ICAM-1)
E. Can trigger rejection
F. Transbronchial biopsy / bronchoalveolar lavage to differentiate

9. Rejection in Lung Transplantation

A. Routine screening
B. Lung allografts more antigenic and more vulnerable to rejection
C. Symptoms: malaise, shortness of breath, lung infiltrate
D. Differentiating infection from rejection difficult
E. Transbronchial biopsy, bronchoalveolar lavage useful
F. Serial daily spirometry (FEV1)

10. Bronchiolitis Obliterans

A. Primary factor limiting long-term survival
B. Exact etiology unknown (chronic rejection/infection)
C. Most important cause of mortality and morbidity after lung transplantation
D. Affects 50% of long-term survivors
E. 50% will respond to enhanced immunosuppression
F. The remainder will have progressive deterioration of lung function

11. Pediatric Lung Transplantation

A. Higher incidence of bypass
B. May be more vulnerable to bronchiolitis obliterans
C. Immune advantage has not been clearly documented in pediatric population

12. Survival after Lung Transplantation

By Diagnosis
Diagnosis30 Days1 Year
Emphysema (SL)93%78%
A1A (SL)90%75%
Cystic fibrosis (BL)90%70%
Pulmonary fibrosis (SL)82%65%
Pulmonary htn. (BL)80%75%
By Transplant
Transplant1 Year5 Years
Single (SL)70%40%
Bilateral (BL)70%48%

EXTENDED OUTLINE

1. Introduction

A. 1963-Hardy @ U Mississippi 1st human lung transplant à 18d survival
B. 1963-83 - 44 lung transplants w/o success [bronchial anastomosis/MOF]
C. 1983 - Toronto Lung Transplant Group @ 6-yr survival

2. End-Stage lung disease

A. Obstructive lung disease
1) Chronic elevation in airway resistance
a) Decreased exp flow rates (FEV1, FVC, FEV1/FVC)
b) Air trapping (­ TLC and FRC)
2) Prognostic factors = age, degree of airway obstruction (FEV1)
3) COPD
4) Alpha-1 antitrypsin deficiency emphysema
a) Lack protection against neutrophil elastase in distal airways
b) Severe bullous emphysema by 4th or 5th decade
B. Cystic fibrosis (CF) (1/2,000 live births)
1) Most common end-stage obstructive disease 1st-3rd decades
2) Thick secretions, poor ciliary fxn => mucus plugging, pulm sepsis
C. Restrictive lung disease - idiopathic pulmonary fibrosis (IPF)
1) Decreased Lung volumes and exp flow
2) Decreased diffusing capacity
D. Pulmonary hypertension
1) Primary pulmonary hypertension (PPH):Mortality correlates w/CVP >10mmHg, PA(mean) >60mmHg, CI<2L/min
2) Eisenmenger’s syndrome:Ca-channel blockers may [increase or decrease???] PA pressures
E. Others: sarcoidosis, chemo/RT-induced fibrosis, lymphangiomatosis

3. Recipient selection

A. Mean waiting time 9-12 mo. (Wash U) 13.5 mo. (US)

4. Preoperative evaluation and management of recipients

A. All pts enrolled in cardiopulmonary rehab

5. Choice of procedure

A. Obstructive lung disease
1) Early single lung transplant (SLT)àhyperinflating native lung, crowding, V/Q mismatch
a) Oversizing donor lung
b) Proper preservation technique
2) SLT for: >55yo, high risk), prior surgery, asymmetric dz
3) Bilateral lung transplant (BLT) for: younger,bilat dz,small donor
B. CF (and other septic lung disease)=> BLT due to infection risk in native lung
C. IPF
1) SLT theoretically ideal- decrease compliance and ­ PA pressures in native lung favor­ allograft ventilation and perfusion
2) BLT for large individual, especially with nl lung volumes
D. PPH - Ht-lung transplant, traditionally
1) SLT has been successful
a) Post-op management difficult, nearly all pulm flow to allograft
b) Late graft problem=severe V/Q mismatch
2) BLT may provide better long-term result

6. Timing of transplantation

A. Pts w/life expectancy 12-24 mo
B. ~30% will receive transplant w/in 1 year
C. Risk of dying on the waiting list:PPH, IPF, CF >>> COPD

7. Other criteria

A. Age (not absolute): BLT=55, SLT=65
B. Ventilatory support- no longer an absolute contraindication (already listed)
C. Corticosteroid therapy - data suggest:
1) low-dose prednisone does not ­ airway complications
2) low-dose steroids may ­ allograft bronchial circulation
D. Prior surgery - no longer a contraindication, in general

7. Criteria for donor lung suitability

A. 20-25% of multiple organ donors have suitable lungs
B. Size - TLC, VC estimated by height/weight - oversize 20% for SLT
C. Donor lung scarcity
1) Use “marginal” lungs
2) Single lung assessment (2-lumen ETT, PA clamping)
3) Living related donor (for pediatric CF patients)

Technique of Lung Preservation and Extraction

1. Lung preservation

A. Prostaglandin E-1 before inflow occlusion (vasodilatation + other benefits)
B. PA flush w/3L cold Euro-collins
C. Extraction of lungs semi-inflated w/100% O2 (grafts use it)
D. Transport under hypothermia (0-1°C)
E. Topical cooling during implantation

2. Donor lung extraction

A. Median sternotomy, dissection
1) Isolate SVC and IVC
2) Separate aorta and PA-Cardiopleg. cannula in aorta, cannulate distal PA
3) Incise posterior pericardium, exposing distal trachea
B. Graft flushing
1) Bolus PGE-1 (500 mg)
2) Inflow occlusion (ligate SVC, clamp IVC)
3) Vent R heart - transect IVC
4) X-C aorta, administer cardioplegia
5) Amputate tip of LA appendage, start lung flush
6) Flood chest w/ iced saline, ventilate w/100% O2
C. Extract heart
1) Transect cavae and aorta
2) LA incision is last, leaving a cuff of atrium
D. Extract lungs
1) Divide trachea between two firings of TA-30
2) (Divide esophagus superiorly and inferiorly)
3) Transect descending thoracic aorta
4) Transport on ice

Lung Transplantation Procedure

1. Anesthetic considerations

A. PA catheter
B. Left-sided 2-lumen ETT
C. Initial bronchoscopy and aspiration for CF patients
D. Avoid “pulmonary tamponade”
E. CPB for:
1) Hemodynamic instability
2) Pulmonary vascular dz
3) Poor allograft function in BLT

2. Technique

A. Incision
1) SLT-posterolateral thoracotomy
2) BLT- bilateral transverse thoracosternotomy (“clamshell”) {5th IC space for COPD, 4th for CF}
B. Choice of side - avoid surgery, remove better lung - in BLT, worse lung transplanted 1st
C. R/O PFO in PPH-intra-op TEE
D. In SLT, CPB is selective - trial of PA clamping

3. Lung implantation

A. Divide 1st PA branch between ligatures, the staple PA trunk
B. Mobilize both pulmonary veins (PV) intrapericardially
C. Transect bronchus-R=just proximal to RUL takeoff, L=1-2 rings above bifurcation- hemostasis
D. Topical cooling - iced gauze around graft
E. Brocnchial anastomosis
1) Continuous 4-0 mono-absorbable for membranous
2) Telescope cartilaginous arches figure-of-8 interrupted sutures
3) Ometopexy no longer used
F. PA anastomosis - 5-0 mono-non
G. LA anastomosis - 4-0 mono-non
H. De-air
1) Antegrade (release PA clamp)
2) Retrograde (release LA clamp)
I. Bronchoscopy

4. Post-operative Management

A. ICU post-op - quantitative perfusion scan
B. Pain control - epidural
C. Ventilator
1) SLT: COPD=no PEEP, PPH=10cm PEEP x 36h
2) Weaning - PPH=sedated, paralyzed x 36h, others=early wean
D. Postural drainage (lat x 24h), chest PT
E. Hemodynamics: dopamine for diuresis, PGE-1
F. Bronchoscopy - OR, POD1, pre-extubation, and prn
G. Infection
1) Abx prophylaxis: CF - per recipient cultures; others, per donor, or ancef x 3-4d
2) HSV prophylaxis: acyclovir 200mg BID for ³ 2 yr
3) PCP:Septra-DS - one bid q M-W-F
4) Candida: nystatin
5) CMV
a) Attempt to match, avoid CMV neg recip/CMV pos donor
b) Prophylaxis=gancyclovir
H. Immunosuppression
1) Triple regimen: cyclosporine, azathioprine, corticosteroids
2) Antithymocyte globulin (ATGAM) x 8 days

5. Follow-up strategies

A. Clinical f/u - remain in town x 3 months
B. PFTs - primarily FEV1 - Monthly in 1st year
C. CXR - schedule similar to PFT’s + prn
D. Bronchoscopy (FOB) with transbrochial bx (TBLB)
1) 3-4wk post-op, 3mo, 6mo, 1yr, then annually
2) Direct TBLB to areas w/infiltrates
E. Open lung bx-when TBLB inconclusive in face of clinical, physiologic deterioration

6. Problems (clinical-pathologic entities encountered in the lung transplant recipient)

A. Acute rejection -more common than other solid-organ allografts
1) Incidence unknown - “virtually all” in 1st 3-4wks post-tx
2) From 1st 3-5 days post-op to years later
3) Clinical manifestation variable-malaise, mild dyspnea, fever, decreased FEV1, decreased PO2
4) Dx:FOB, TBLB => 84% sens, 100% spec (Ht-lung tx)
5) Tx: High-dose steroids, ­ maintenance prednisone, ATGAM or OKT3 for refractory episodes
B. CMV infection
1) May mimic rejection
2) Dx by TBLB
3) Tx w/gancyclovir (documented infection)
C. Chronic rejection/Bronchiolitis Obliterans syndrome (BOS)
1) Inflammatory disorder of the small airways-histologically, dense fibrosis and scar obliterating bronchial wall and lumen
2) Prevalence as high as 50%
3) Dry or productive cough, dyspnea refractory to bronchodilators
4) Airflow obstruction with progressive ¯ in FEV1
5) Tx: ­ Immunosuppression (empiric)-most pts will progress
D. Bronchial anastomotic complications
1) Usually result from ischemia which =>
a) Air leak or mediastinal collection (early)
b) Stenosis or malacia (late)
2) New dyspnea, stridor or wheeze
3) W/U=CXR, FOB, chest CT
4) Tx:
a) Early (dehiscence) = drainage and conservative measures
b) Late (stricture or malacia) - stent

7. Results

A. Survival
1) 92% hospital survival
2) 70% 1-yr, 43% 5-yr
3) Small benefit of BLT vs SLT (not significant)
B. Functional results
1) FEV1, ABG, 6-minute walk improved
2) FEV1, PaO2, significantly better after BLT vs SLT
3) BLT associated w/ higher complication rate
C. Pulmonary vascular dz
1) Decreased PAS, CVP, PVRI
2) NYHA class III-IV => I-II