Lung Transplantation

Role of chest physicianEsen Kıyan

İstanbul Üniversitesi İstanbul Tıp Fakültesi

Göğüs Hastalıkları Anabilim Dalı

Content

-Disease specific transplantation indications (2006 ISHLT concensus)

-Contraindications

-Preoperative preperation

-Postoperative follow-up (therapy and complications)

Factors affecting survival and waiting time on the waiting list

Blood group, height, BMI Type of pulmonary

disease Age Systemic dis. (DM) 6MWT, functional status MV PHT

Early referral for consideration of Tx is highly desirable

Timing of referral

-Two-three year predicted survival <%50

-NYHA class III or IV

COPD

Timing of referral BODE index >5

BODE indx of 7 to 10 or at least one of the following:

-History of hospitalization for exacerbation associated with acute hypercapnia (PaCO2 exceeding 50mmHg)

-PHT or cor pulmonale or both (despite oxygen therapy)

-FEV1<%20 + DLCO<%20 or homogenous emphysema

TP

IPF and NSIP

Histologic or radiographic evidence of UIP (irrespective of VC) or histologic evidence of NSIP

Histologic or radiographic evidence of UIP and any of the following:

-DLCO<39% predicted-A 10% or more decrease in FVC during 6 months of follow-up-A decrease in pulse oximetry below 88% during a 6MWT-Honeycombing on HRCT (fibrosis score >2)

TP

Pulmonary arterial hypertension

NYHA class III or IV (irrespective of ongoing therapy)Rapidly progressive disease

Persistent NYHA class III or IV on maximal therapy

Low (<350 meter) or declining 6-MWT

CI<2L/dk/m2

Right atrial pressure>15mmHg

Failing therapy with iv epoprostenol or equivalent

TP

Cystic Fibrosis/Other causes of Bronchiectasis

FEV1<30% pred. or a rapid decline in FEV1(in particular young female patients)Exacerbations requiring ICU stayIncrease in the frequency of exacerbations requiring antibiotic therapyRefractory and/or recurrent pneumothoraxRecurrent hemoptysis not controlled by embolization

Oxygen-dependent RFHypercapniaPHT

TP

Sarcoidosis

NYHA class III or IV

Hypoxemia at restPHTRight atrial pressure>15mmHg

TP

Contraindications-I

Absolute Contraindications

Active malignancy (<2 years)Extrapulmonary organ failure (liver, renal, hearth)Chronic active hepatitis, hepatitis C, HIV(+)Severe chest wall and spinal deformityNonadherence to treatment and follow-upUntreatable psychiatric conditionsAbsence of social support systemSubstance addiction (tobacco, alcohol, narcotics)

Contraindications-II

Relative contraindications

-Age>65, BMI>30kg/m2 or <17kg/m2-Critical or unstable clinical condition (shock, MV, ECMO)-Severely limited functional status with poor rehabilitation potential-Colonization with highly resistant or virulent bacteria, fungi, or mycobacteria-Severe or symptomatic osteoporosis-Systemic diseases (without organ dysfunction)-Retransplantation

Basic evaluation for referral to the transplantation center

-Indications/contraindications

-LTOT-NMV requirement

-LFT, ASG, 6MWT

-Basic laboratory tests

-ECG and Echocardiography

-Torax CT (last 6 months) + HRCT

-Dental evaluation, gynecological and breast check-up, PSA

Special tests for evaluation before listing

-Viral serology (HIV, HBV, HCV, CMV, EBV)

-Sputum culture, ENT examinetion (bronchiectasis, CF)

-Carotid US (>45)

-Coronary angiography (>45)

-Colonoscopy (>50 yaş)

-Quantitative V/Q scan (mandatory for SLTx)

-Right hearth catheterisation (PHT)

Immunosuppressive therapy

Cyclosporine A (Tacrolimus)

AND

Azathioprine (Mycophenolate M)

AND

Steroid

Induction therapy (OKT3, ATG, Daclizumab, Basiliximab)

Cyclosporine

Tacrolimus Azathioprine

MycophenolateMofetil

Steroid

Preop 5mg/kg PO 0.05mg/kg PO 2.5 mg/kg PO

If <50kg, 750mgIf >50kg, 1000mg

500mg iv

Intraope. ---- ---- ---- ------ 500mg iv/each lung

Postop (PO)

4mg/kg, 2x1 po

0.05mg/kg 2x1 po

2.5mg/kg 1x1 po

2x1 poIf<50kg, 1000mgIf>50kg, 1500mg

125mg3x1 po, later 1mg/kg 2x1

Postop (IV)

40mcg/kg/hr continuous inf.

1mcg/kg/hr continuous inf.

1-1.25 mg/kg/day

1-1.5g, 2x1 125mg, iv, 3x1, later 2mg/kg/day iv ( in 3 doses)

P. Carinii prophylaxyAzitromycin (after one week)

Fungal prophylaxy (first 2 weeks voriconazole 200mg iv/po, 2x1And inhaler Amphotericin B (3 months)

Postop antibiotic prophylaxy (7-14 days)

VIRAL PROPHYLAXY

CMV status Prophylaxis Time

D (-) /R (-) Valacyclovir po 1x500mg Lifi time

D (+) /R (+) or D (-) /r (+)

Gancyclovir 5mg/kg iv 2x1Valgancyclovir po 2x900mg

1-14 days

Valgancyclovir 1x900mg 15-180 days

Valacyclovir 1x500mg 181-life time

D (+) /R (-) Gancyclovir 5mg/kg iv 2x1 1-14 days

Valgancyclovir po 2x900mg 15-45

Valgancyclovir po 1x900mg 46-180

Valgancyclovir po 1x500mg 181-life time

Irrespective of CMV status

CMV Ig 200mg/kg Days:0,3,14,28 ve 56

Chest X ray/day

IS drug level monitorization/day

Bronchoscopy Postop 1st day, prolonged entubation, just before extubation (BAL)

CMV-PCR and fungal serologySputum culture

ICU PERIOD

Chest X ray, laboratory tests, IS drug level

CMV-PCR + fungus serology/week

Thorax CT+ PFT

Bronchoscopy during follow-upBefore e.ternationx 2, 4., 8, 12th weeks; 6. and 12th weeksLater if you think rejection

B) AFTER ICU

Outpatient clinic follow-up

LFT, ABG, blood tests, Ches X ray

Sputum culture, CMV-PCR

Bronchoscopy (2,4,8,12. weeks, 6 and 12th months, once in a year or if acute or chronic rejection)

Osteoporosis evaluation (bone densitometry/ year)

Fever, leucocytosis, infiltration

Infection?

Acute rejection?

BAL + TBB

Start tretament for both condition

Rejection? or infection?

Post-transplant problems

Hemorrhage

Primary graft dysfunction

Anastomose problems

Hyperacute rejection (HLA antibody)

Arytmia

Acute rejection

Infection (bacterial, viral, fungal)

Airway complications

PE

Chronic rejection (BOS)

Complication <72h 72h-1 week >1 week >1 month

Bleeding x

Technical x

PGD x(COMMON)

Arythmia x X

Infection X X X

Rejection X (uncommon) X X

Pulmonary emboli X X

BO/BOS X

Post-transplant problems

Reaction between IS drug and other drugs

Renal failure, DM, KV (HT, HL)

Osteoporosis, avascular necrosis of femur

Bone marrow suppression

Malignancy and PTLPD

GER

CONCLUSION

To decrease postop mortality:

-Select candidate

-Be careful for timing of referral

-Correct diagnosis and treatment of postop early and late complications