Main.LungTransplantation History

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%center%%blue%''''+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
||border=1 width=80%
|| Diagnosis || 30 Days ||1 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
||border=1 width=80%
|| Transplant || 1 Year || 5 Years ||
|| Single (SL) || 70% || 40% ||
|| Bilateral (BL) || 70% || 48% ||

%center%'''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&#146;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 &#147;marginal&#148; lungs
-->2) Single lung assessment (2-lumen ETT, PA clamping)
-->3) Living related donor (for pediatric CF patients)

%center%'''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

%center%'''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 &#147;pulmonary tamponade&#148;
->'''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 (&#147;clamshell&#148;) {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&#146;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 - &#147;virtually all&#148; 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