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LUNG TRANSPLANTATION

Dr. Pratik Kumar

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Overview :• Introduction • Purpose of lung transplantation • History• Indications • Disease specific selection criteria • Contraindications

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Overview :

• Description • Laboratory studies • Donor-related issues • Preoperative care • Post operative care • Complications • Normal results

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Introduction :

• Lung transplantation involves removal of one or both diseased lungs from a patient and the replacement of the lungs with healthy organs from a donor

• Lung transplantation may refer to single, double, or even heart-lung transplantation .

• Lung transplantation is an accepted modality of treatment for end stage lung disease that is unresponsive to medical therapy

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Purpose :

• To replace a lung that no longer functions with a healthy lung.

• To perform a lung transplantation, there should be potential for rehabilitated breathing function.

• Other medical treatments should be attempted before transplantation.

• Many candidates for this procedure are dependent on oxygen therapy

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History of procedure :• Animal experimentation by various pioneers,

including Demikhov and Metras, in 1940s and 1950s demonstrated that the procedure is feasible technically.

• First human lung transplantation was done in 1963. The donation was essentially after cardiac death, and the recipient of the left lung transplant survived only 18 days.

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Cont……….d:

• From 1963-1978, multiple attempts at lung transplantation failed because of rejection and problems with anastomotic bronchial and tracheal healing.

• The first successful single lung transplant was reported by Dr. Joel Cooper at the University of Toronto in 1986 .

 

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Cont……….d:• In 1988, Dr. Alexander Patterson described the

technique of double-lung transplantation. • Dr. Denton Cooley and associates were the

first to attempt heart-lung transplantation in 1968.

• First heart-lung transplant in India- 3 May 1999 at Madras Medical Mission.

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AGE DISTRIBUTION OF LUNG TRANSPLANT RECIPIENTS

0

5

10

15

20

25

18-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-65 66+

Recipient Age

% o

f tr

an

sp

lan

ts

J Heart Lung Transplant 2008;27: 937-983

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Indication of lung transplantation :• Obstructive lung disease: A. Chronic obstructive pulmonary disease• Restrictive lung diseases: A. Idiopathic pulmonary fibrosis (IPF) B. Interstitial lung disease

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Indication of lung transplantation :

• Septic lung disease: A. Cystic fibrosis (CF) B. Bilateral bronchiectasis • Pulmonary vascular disease: A. Primary pulmonary hypertension (PPH) B. Eisenmenger’s syndrome

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Diagnosis of Lung Transplant Recipients in US (1986-2007)

40%

13%13%

8%

14%

2%4%

1% 4% 1% COPD

Alpha I Anti Def

IPF

Other

Cystic Fibrosis

IPAH

Talcosis

BO

Eisenmenger's

Bronchiectasis

J Heart Lung Transplant 2008;27: 937-983

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Disease specific selection criteria

COPD- Pt. with BODE index 7 to 10 of at least 1 of

the following:1. FEV1 < 25% predicted ( without

reversibility)2. PaCO2 >55 mm of Hg3. Elevated pulmonary artery pressure (PAP)4. Cor pulmonale

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Cont……….d: Other indices shown to correlate mortality- 1)subjective breathlessness 2)weight loss 3)exercise tolerance 4)hospitalization 5) lung morphology all patients requiring hospitalization for

exacerberation should be considered for surgery

1 year mortality after hospitalization -23%

The BODE Index For COPDThe BODE Index For COPD

Can Fam Physician 2008;54:706-11Can Fam Physician 2008;54:706-11

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Cont……….d:

IPF-• Highest attrition rate with waiting list

mortality 30%• Initially, owing to unpredictable nature of

course, view was to refer all patients for transplantation at diagnosis

• Patients with exercise induced desaturation are ideal candidates

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Cont……….d:

Current consensus- 1) Symptomatic progressive disease despite 3 months of medical therapy 2) Rest or exercise induced desaturation 3) Symptomatic with- VC< 60-70%predicted DLCO < 50-60% pred.

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Cont……….d: Cystic fibrosis Prognostic criteria- 1)age per year 2)sex 3)FEV1 4)weight for age 5)Pancreatic insufficiency 6)D.M. 7)S.aureus 8)B.cepacia 9)No. of acute exacerberations

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Cont……….d:

• Patients divided into 5 prognostic groups• Only group 1&2 with 5 year survival rate <30%

benefited• Resistant B. cepacia infection is absolute

contraindication

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Cont……….d:

PPH• Advancement in medical management-

reduced need for transplantation• 1990- 10.5% of all cases• 2001- 3.6% of all cases

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Cont……….d:

• Criterias for PPH Symptomatic progressive disease

despite optimal medical treatment for 3 months

Cardiac index < 2 lit/min/m2Right atrial pessure>15 mm HgPAP mean > 55 mm Hg

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Cont……….d:

Eisenmengers syndrome • Better prognosis than patients with

PPH with similar PAP levels• Epoprostenol therapy improved

survival & reduced need for transplantation• Heart -lung transplantation is preferred

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Cont……….d:

Sarcoidosis • Most patients benign course 10-20%

permanent sequel• 2.5% of all transplants• Only stage 4 disease is considered• FVC < 50% & FEV1 < 40%

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Cont……….d:

Lymphangioleiomyomatosis • FEV1/FVC < 45%• Average from diagnosis to transplant -

11yr

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Contra-indication (Absolute ):

• Malignancy in the last 2 years• Non-curable chronic extra pulmonary

infection including chronic active hepatitis B , C , and HIV

• Untreatable advanced dysfunction of another major organ system

• Current cigarette smoking

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• Poor nutritional status

• Poor rehabilitation potential

• Significant psychosocial problems

• Substance abuse history of medical noncompliance

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Relative Contraindications :

• Age : advanced age is associated with higher mortality rates .

• Most centers have an age cut-off 50 years for -Heart-lung transplantation, 60 years for- Bilateral lung transplantation, 65 years for -Single-lung transplantation.

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• Ventilator dependence : patients who are dependent on a ventilator prior to the transplant have higher mortality rates .

• A prolonged wait while the patient is on a mechanical ventilator may lead to various complications such as infections, cardiovascular de-conditioning.

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• Psychosocial issues : Individuals who currently smoke, abuse drugs, or drink alcohol heavily are not candidates for transplantation.

• Patients with other psychosocial issues, such as poor compliance and psychiatric disorders that may complicate post transplant therapy, are not considered good candidates.

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• Infection : patients who have active tuberculosis infection are not candidates for transplantation.

• Body weight : Patients who have poor nutritional status and would have a poor outcome following transplantation.

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• Obesity (BMI >30) : also may be a concern because of postoperative atelectasis and pneumonia • Extra pulmonary organ dysfunction :

Patients with a significant heart, liver, or kidney disease are not transplant candidates.

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Description :

• Single lung transplantation is performed via a standard thoracotomy (incision in the chest wall) with the patient under general anesthesia.

• Cardiopulmonary bypass (diversion of blood flow from the heart) is not always necessary for a single lung transplant.

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Cont………..d:

• If bypass is necessary, it involves re-routing of the blood through tubes to a heart-lung bypass machine. Double lung transplantation involves implanting the lungs as two separate lungs, and cardiopulmonary bypass is usually required

• The patient's lung or lungs are removed and the donor lungs are stitched into place. Drainage tubes are inserted into the chest area to help drain fluid, blood, and air out of the chest.

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FigurePatient positioned for bilateral lung transplant, through a clamshell incision with the arms abducted. The skin incision is depicted in the mammary fold heading laterally toward the mid-axillary line. The dotted line shows the level of the 4th intercostal space. The position of the femoral artery, on both sides, is also marked. The groin is prepped and draped, since during the transplant procedure, an arterial femoral line may become necessary for monitoring or even for cannulation for cardiopulmonary bypass.

ADULT LUNG TRANSPLANTATION: Indications for Single Lung Transplants (Transplants: January 1995 - June 2007)

50%

28%

2%1%

2%

7%

10%

Alpha-1 COPD CF IPF PPH Re-TX Other*

*Other includes:

Sarcoidosis: 2.1%

Bronchiectasis: 0.4%

Congenital Heart Disease: 0.2%

LAM: 0.7%

OB (non-ReTx): 0.5%

Miscellaneous: 5.8%

J Heart Lung Transplant 2008;27: 937-983

ADULT LUNG TRANSPLANTATION: Indications for Bilateral/Double Lung Transplants (Transplants: January 1995 - June 2007)

24%

14%

18%

8%

28%

6% 2%

Alpha-1 COPD CF IPF PPH Re-Tx Other*

*Other includes:

Sarcoidosis: 3.0%

Bronchiectasis: 4.8%

Congenital Heart Disease: 1.3%

LAM: 1.2%

OB (non-ReTx): 1.1%

Miscellaneous: 6.6%

J Heart Lung Transplant 2008;27: 937-983

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Laboratory studies :

• The following diagnostic tests are usually performed to evaluate a patient for lung transplantation:

• Arterial blood gases (ABG ) test: which measures the amount of oxygen that the blood is able to carry to body tissues.

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• Pulmonary function tests (PFTs): which measure lung volume and the rate of air flow through the lungs; the results measure the progress of the lung disease.

• Computerized tomography (CT) scan. A chest CT scan is taken of horizontal slices of the chest to provide detailed images of the structure of the chest.

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• Ventilation perfusion scan (lung scan, V/Q scan) is a test that compares right and left lung function

• Electrocardiogram (ECG): is performed by placing electrodes on the chest. A recording of the electrical activity of the heart is obtained to provide information about the rate and rhythm of the heartbeat

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• Echocardiogram (ECHO) is performed to evaluate the impact of lung disease on the heart. It examines the chambers, valves, aorta, and the wall motion of the heart.

ECHO also provides information concerning the blood pressure in the pulmonary arteries. This information is required to plan the transplantation surgery.

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• Blood test : Complete blood count , Coagulation profile.

• HIV, hepatitis B, hepatitis C

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Donor-related issues:

• Younger than 65 years for lung transplantation and younger than 45 years for heart-lung transplantation

• Absence of severe chest trauma or infection • Absence of prolonged cardiac arrest (heart-

lung only) • Minimal pulmonary secretions Negative

screens for HIV, hepatitis C, and hepatitis B

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• Blood type (ABO) compatibility • Close match of lung size between donor and

recipient • PaO2 > 300 mm Hg on 100% fraction of

inspired oxygen • Clear chest radiograph • No history of malignant neoplasms

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Preoperative care:

• Preoperative assessment consist of both medical & psychosocial evaluation.

• Assessment of patient‘s physical health is assessed to determine candidacy for transplantation.

• In preoperative phase the patient is assessed for cardiac output & renal functions .

• Psychosocial evaluation focuses on assessing the patient‘s history of compliance with medical therapy & ability to cope with stress.

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Post operative care :

• The patient is observed for excessive bleeding. • Monitor vital signs ,ECG ,ABG values ,urine

output, O2 level analysis & chest tube drainage.

• The patient may be started on mechanical ventilation for 24 to 48 hours.

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• Serum electrolytes ,complete blood count, chest radiographs are obtained daily.

• Fluids are restricted. • Lung sounds are auscultated. • Severity of peripheral edema is monitored. • Pain control is important to allow deep

breathing & coughing with chest physiotherapy.

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• The patient with lung transplantation is at high risk to develop infection.

• So isolation is used to decrease exposure to pathogens.

• Monitor the patient for clinical manifestation of infection such as:

Change in vital signs especially fever Local infection at i/v site & incision line Changes in respiratory status like excessive secretions, tachypnea,dyspnea

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Immunosuppression

• Induction phase- A) ATG B) Selective IL2 receptor antagonists• Maintenance phase- A) Steroid + calceneurin inhibitor B) Steroids ( low dose ) life long C) Tacrolimus for 1-5 years

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Newer drugs

1) Sirolimus (Rapamycine)- An analog of Tacrolimus

2) Everolimus- used in combination with cyclosporin & prednisolone shown to have freedom from biopsy proven acute rejection in 88% cases

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Complications • Causes of respiratory failure after LTx

Early• ischemia reperfusion

injury• infection• technical problems• acute rejection

>3months• Infections• BOS

Curr.opin.Crit.care 2006 Feb;12, 19-24

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Ischemia reperfusion injury

Most frequent cause of early mortalitypresents as ALI / ARDSReduced incidence since 1990- 1) low K- dextran solution 2) nitric oxide added to flush solution 3) prevention of hyperinflation during harvesting 4)controlled reperfusion with leucocyte

depletion

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Ischaemia reperfusion injury contd.

• Treatment- A) diuretics B) maximal ventilatory support• Newer modalities A) inhaled nitric oxide B) inhaled prostacyclin• Course- resolves in 48-72 hrs

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Infections• Bacterial- A) psuedomonas predominate in early post

op(75%) B) nocardia-2.1% C) legionella , mycobacteria rare • routine antibiotic prophylaxis reduced the

incidence• sputum cultures & antibiotic sensitivity done every

3 months

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Viral infections

CMV predominates• within 30-100 days after transplant • occurs as reactivation or prim. infection

(donor) • incidence varies between 13-75% in various

studies• routine prophylaxis replaced by close

monitoring• Treatment-gancyclovir 5mg/kg for 2-3 weeks

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• HSV&VZV can cause pnuemonia• Acyclovir prophylaxis effective in patients not on

gancyclovir• EBV related post-transplant lymphoproliferative

disease• 4-10% cases• usually fatal outcome• recently Rituximab ( anti CD20 Ab) found effective

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Fungal infections

• Aspergillus most common 1) ulcerative trachitis 2) bronchitis 3) pnuemonitis 4) disseminated diesase 5) ABPA- reported• I.V. or aerolised ampho-B used for prophylaxis

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Other rarer organisms

• Histoplasma• Sedosporium• Pnuemocystis jirovecii

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Rejection

• Acute rejection-• < 7 days onset• low grade fever, dyspnoea• CXR- 1) Clear 2) illdefined infiltrates 3) pleural effusion• reduced FEV1

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Acute rejection

• TBLB - gold standard in diagnosis• Noninvasive means-area of active research 1) Cytokine milieu in BAL fluid 2) gene upregulation as a biomarker• Treatment- bolus I.V. steroids + increase in

maintenance immunosuppression• role of surveillance bronchoscopy to detect

rejection early is controversial

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Chronic rejection

Bronchiolitis Oblitrance Symdrome (BOA) :• Predominantly a small airway disease• occurs in 50% patients surviving for 5 years• onset > 6months• major cause of mortality• CXR- can be normal late cases- bronchiectesis• HRCT- mottled appearance with peripheral

lucency

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TBLB- gold standard• Role of induced sputum & BAL- 1) Induced sputum – RANTES levels and

eosinophils correlate with BOS development

2) BAL- IL8 & neutrophil levels have negative correlation

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• Treatment- variable course even without treatment

• various immunosuppressive regimens tried

• macrolides under evaluation

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• Factors associated- 1) CMV pnuemonitis -no. of episodes 2) HLA mismatch 3) GERD- laproscopic fundoplication reduces incidence

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Self care :

• Before discharge the patient should be teach about the medication regimen.

• The patient should report for fever, dyspnea, cough ,increased sputum production ,chest pain, excessive weight gain, fatigue to physician. During follow up the client is monitored for manifestation of rejection & progress in functional status.

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• Exercise capacity has been the most interesting functional outcome observes in lung transplant recipient .

• Typically transplant recipient can walk 100 to 120m/min within 6 months of transplantation.

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Normal results:

• Demonstration of normal results for lung transplantation patients include

a) adequate lung function, b) improved quality of life, c) lack of infection and rejection.

68http://articles.timesofindia.indiatimes.com/2012-07-31/mumbai/32960286_1_lung-transplants-

transplant-team-surgery

Cost of Lung Transplantation in India

• Surgery alone cost Rs 10 lakh.• The ICU and medications will work up to

an equal amount

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THANK YOU