Lung transplantation is a viable alternative for end-stage lung diseases, which offers good quality of life and survival outcomes for recipients. The aims of pre-assessment for potential lung transplant recipients are to assess fitness for surgery, optimise co-morbidities, commence interventions or investigations, weigh risk–benefit ratio, plan appropriate analgesia and obtain informed consent. The assessment information is gathered from the medical record, patient interview, physical examination and pre-operative tests. A comprehensive workup includes cardiopulmonary evaluation, haematological, biochemical, microbiological and immunological investigations.
Most of the evidence regarding lung transplantation is gleaned from retrospective data from single, multi-centre or multinational registries. The lack of good quality evidence means that the guidelines are based on expert consensus.
Introduction
Lung transplantation is a successful treatment for various end-stage lung disorders, which offers good quality of life (QoL) and survival outcomes for recipients . The shortage of donor organs means that the altruistic gift of these precious resources should be used in recipients with the best likelihood of a beneficial long-term outcome. It is important to ascertain that there is no alternative treatment to lung transplantation. Moreover, a transplant is recommended when the mortality rate due to the natural history of the primary disease exceeds the expected post-transplant survival.
The patient is placed on a waiting list after a comprehensive assessment of the diagnosis, current condition, rate of deterioration and co-morbidities. Pre-operative assessment of potential lung transplant recipients needs a multidisciplinary approach. This team includes the surgeon, respiratory physician, anaesthesiologist, psychologist, dietician, physiotherapist, microbiologist and intensivist. The aims of pre-assessment are to evaluate fitness for surgery, optimise co-morbidities, initiate investigations or referrals, weigh risk–benefit ratio, plan appropriate analgesia and obtain informed consent. As a part of the team, the anaesthetist/intensivist plays a special role in assessing the suitability of the patient as a recipient.
The assessment process also involves communication among healthcare professionals and between healthcare professionals and patients/caregivers. In this article, we aim to discuss the assessment of patients with end-stage lung disease for potential lung transplantation through a practising anaesthetist and intensivist’s point of view.
Evidence base
There is little mention in the literature about the anaesthetic assessment for lung transplant recipients. Most of the evidence regarding lung transplantation is gleaned from retrospective data from single, multi-centre or multinational registries. The lack of good quality evidence from multi-centre randomised controlled trials means that the guidelines from august bodies such as International Society for Heart and Lung Transplantation and European Respiratory Society are based on consensus agreement of opinions of experts.
Evidence base
There is little mention in the literature about the anaesthetic assessment for lung transplant recipients. Most of the evidence regarding lung transplantation is gleaned from retrospective data from single, multi-centre or multinational registries. The lack of good quality evidence from multi-centre randomised controlled trials means that the guidelines from august bodies such as International Society for Heart and Lung Transplantation and European Respiratory Society are based on consensus agreement of opinions of experts.
Timing of referral
Early referral of potential recipients allows for satisfactory pre-operative assessment, additional diagnostic tests, pulmonary rehabilitation and patient education. A referral should only be considered in patients who continue to deteriorate despite optimal therapy and meet the minimum listing criteria. A 2–3-year predicted survival of <50% or New York Heart Association (NYHA) class III or IV level is an indication for referral .
Disease-specific considerations
Lung transplantation is performed in a heterogeneous population with various end-stage lung disorders. Knowledge of the natural history of the primary disease and disease-specific prognostic factors is crucial in the assessment process for potential transplantation.
Chronic obstructive pulmonary disease
Chronic obstructive pulmonary disease (COPD) is the most common (36.5%) indication for lung transplantation . The BODE index is a multidimensional grading system, which includes the body mass index (BMI), the degree of airflow obstruction, dyspnoea and exercise capacity (6-min walk test, 6MWT) to predict mortality . Patients with COPD usually have good survival even with end-stage disease, and lung transplantation may be considered in a select group of patients for improving QoL .
Idiopathic pulmonary fibrosis
Idiopathic pulmonary fibrosis (IPF) or usual interstitial pneumonia (UIP) is the second most common (29.7%) indication for transplantation. Nonspecific interstitial pneumonitis is typically associated with slow progression and longer survival. Patients with combined pulmonary fibrosis and emphysema who develop pulmonary arterial hypertension (PAH) have a poor prognosis despite having moderately abnormal lung function . To date, there is no pharmacological treatment or cure for IPF, but lung transplantation is the only available solution. Early referral is advised as these patients deteriorate quickly and have poor survival rates.
Cystic fibrosis
The multi-system nature of cystic fibrosis (CF) poses a unique challenge for reliable prognostic models because of the highly variable prognosis between different individuals. Chronic infections with antibiotic-resistant organisms, e.g. Burkholderia cepacia complex, liver dysfunction, diabetes mellitus, osteoporosis, sinus disease and gastroesophageal reflux disease, provide an additional layer of complexity. Non-CF bronchiectasis is a rarer indication (2.7%) . Despite the complexity of the disease, the younger age of these patients tends to have a favourable effect on their post-transplantation survival rates. The proportion of lung transplants for CF (15.8%) has significantly decreased over time, especially in paediatric patients because of improved medical care and better survival rate .
Pulmonary arterial hypertension
Idiopathic PAH or secondary PAH is a declining indication (4.4%) for lung transplantation because of improvements in drug therapy . Extra corporeal life support (ECLS) may be required in patients with pre-operative severe right ventricle dysfunction/dilatation, moderate to severe tricuspid regurgitation, increased pulmonary artery pressure (PAP) and oxygen requirement . Other recently evaluated factors associated with increased mortality are frailty, poor physical activity and anxiety disorder .
Sarcoidosis
Sarcoidosis represents 2.5% of indications for adult lung transplantation . In many ways, prospective recipients have similar risk characteristics to IPF . Stage IV sarcoidosis as characterised by advanced fibrosis, honeycombing, hilar retraction and emphysema should be considered for transplantation .
Miscellaneous indications
Lymphangioleiomyomatosis, tuberous sclerosis, lung cancer, non-transplant obliterative bronchiolitis and re-transplantation are some of the other indications for lung transplantation.
Investigations
A comprehensive investigation workup includes pulmonary function tests; cardiac evaluation; and haematological, biochemical, microbiological and immunological studies ( Table 1 ). Repeat radiographs and laboratory and cardiac investigations may be necessary before the surgery, depending on the timing of the last evaluation.
| 1. Pulmonary function tests : Pulmonary function tests including diffusing capacity of the lungs for carbon monoxide (DLCO), arterial blood gas, 6MWT, ventilation perfusion (V/Q) scan |
| 2. Cardiac function tests : Electrocardiogram, 2-D echocardiogram including pulmonary artery pressures, multiple-uptake gated acquisition scan, coronary angiography, cardiac catheterization and right heart catheter. |
| 3. Haematological tests : Full blood count, ABO blood group, coagulation profile, HLA typing, anti-HLA antibodies and panel reactive antibodies. |
| 4. Biochemical tests : Serum electrolytes, blood urea, serum creatinine, liver function tests, blood glucose, lipid profile and thyroid function tests. |
| 5. Infection screen : Culture of sputum/bronchoalveolar lavage, throat and sinus swabs, midstream urine, Gram stain, culture sensitivity, assessment of vaccination status, Mantoux skin test (previous tuberculosis exposure), serology for human immunodeficiency virus (HIV), cytomegalovirus status, Epstein–Barr virus, chlamydia pneumonia, varicella zoster, herpes virus, hepatitis (A, B, C) and toxoplasma. Antibiotic susceptibility testing, in vitro synergy testing |
| 6. Autoimmune screen : antinuclear antibody (ANA), extractable nuclear antigens (ENA), deoxyribonucleic acid (DNA) antibody, rheumatoid factor, anti-neutrophil cytoplasmic antibody (ANCA), creatine kinase and immunoglobulins |
| 7. Radiological studies : Chest X-ray, CT chest and abdominal sonography/CT scan (signs of portal hypertension, nasal sinus) |
| 8. Bone density scan |
Imaging of potential lung transplant recipients
Advances in medical imaging and individual expertise in specialist transplant centres help make an accurate diagnosis . All potential recipients should have a routine plain chest film. A CT scan of the thorax provides information on the primary pulmonary diagnosis, lung volumes, pulmonary hypertension, and lymphadenopathy and excludes malignancy and coronary artery calcification. MRI scanning offers better resolution and dynamic imaging of diaphragmatic movement, which is important in predicting post-transplantation recovery.
Coronary angiography is indicated in patients with cardiovascular risks. Transthoracic echocardiography provides objective measure of the right and left ventricular function and estimates PAP. Lung perfusion scanning is useful in deciding the suitability and side of single lung transplantation.
Indications for lung transplantation
Traditional indications for lung transplant listing are presented in Table 2 . Patients with end-stage lung disease likely to die within 2 years and those with >80% post-transplant survival should be considered for transplant . Attitude of patient and his/her family towards transplantation also plays an important part in the decision-making.
| 1. End-stage lung disease as a result of advanced cystic fibrosis, emphysema, idiopathic pulmonary fibrosis and primary pulmonary hypertension failing maximum medical therapy. |
| 2. Appropriate psychological and medical behaviour. |
| 3. Adequate social setup for post-operative care. |
| 4. COPD : ≥3 severe exacerbations in 1 year, BODE score >7, homogenous distribution of emphysema, acute exacerbation with PaCO 2 >50 mmHg, FEV 1 <20% predicted, DLCO <20% and PAH. |
| 5. IPF : Histologic or radiographic evidence of UIP, DLCO <40% or >15% decrement in 6 months, FVC <60% or >10% decrement in 6 months, 6MWT <250 m or SaO 2 <88%, honeycombing on HRCT and PAH. |
| 6. Cystic fibrosis : Females <20 years, recurrent ICU admissions, FEV 1 <30%, Chronic respiratory failure: PaCO 2 >50 mmHg, PaO 2 <60 mmHg, long-term non-invasive ventilation and PAH. |
| 7. PAH : NYHA class III or IV on maximal medical therapy, 6MWT <350 m, right heart failure: cardiac index (CI) <2 L/min/m 2 , right atrial pressure (RAP) >15 mm Hg . |
| 8. Sarcoidosis : NYHA class III or IV, Hypoxemia at rest and RAP >15 mmHg |
Contraindications for lung transplantation
A holistic approach, which weighs the risks posed by co-morbidities and contraindications against the obvious benefits of transplantation, is needed . The absolute and relative contraindications are given in Tables 3 and 4 respectively.
| 1. Recent history of malignancy. Less than a 2-year disease-free interval with a low recurrence risk or <5-year disease-free interval in patients with history of haematologic malignancy; sarcoma; melanoma; or cancers of breast, bladder or kidney. |
| 2. Significant major organ dysfunction or limited functional status. |
| 3. Acute serious medical condition (e.g. sepsis). |
| 4. Untreatable coronary artery disease/atherosclerosis. |
| 5. Uncontrolled bleeding conditions. |
| 6. Highly virulent chronic infections (e.g. tuberculosis). |
| 7. Significant chest wall/spinal deformity. |
| 8. BMI >35 kg/m 2 . |
| 9. Psychiatric/psychological conditions including substance abuse and non-compliance with medical therapy. |
| 10. Lack of social support. |
| 1. Age >65 years |
| 2. BMI >30.0–34.9 kg/m 2 or severe malnutrition/osteoporosis |
| 3. Prior thoracic surgery such as pleurodesis or lung volume reduction surgery (LVRS) |
| 4. Mechanical ventilation and/or extra corporeal life support (ECLS) . |
| 5. Colonization or infection with highly resistant/virulent bacteria, fungi or virus [non-tuberculous mycobacteria (NTM), Hepatitis C, HIV, Burkholderia cenocepacia , etc.] |
Predictors of survival
Prognostic factors and predictors of survival help identify worsening patients on the waiting list and predict post-transplantation survival ( Table 5 ).
| COPD : Older age, oxygen requirement, poor lung function/exercise capacity, lower lung zone emphysema, More than three infections in 1 year, BMI <20, higher BODE score . |
| IPF : Older age, dyspnoea, respiratory hospitalization, concomitant emphysema and poor lung function/exercise capacity (percentage predicted FVC and 24-week change in FVC) . |
| Cystic fibrosis : older age, height, FEV 1 < 30%, need for nutritional supplements, pneumothorax, NTM/ B. cepacia complex infections, number of hospitalizations/home intravenous antibiotic courses, 6MWT <400 m . |
| Pulmonary hypertension : NYHA class IV, right heart failure, NYHA class III to IV or failure of pulmonary vascular resistance to decrease by 30% even after vasodilator therapy . |
| Sarcoidosis : RAP >15 mmHg, Decreased CI, hypoxemia and increased PAP. |
Patient specific considerations
Psychological assessment
Lung transplant candidates experience a variety of psychosocial stressors throughout the peri-transplant phase, which affects their QoL, physical function, psychiatric status and compliance . They also appear to have a lower QoL than candidates for other types of transplantation. A thorough psychological assessment, including the recipient’s motivation, compliance, QoL and the social environment, by an experienced practitioner is essential for successful outcome . It is important to identify behavioural traits (e.g. poor compliance) that may render the patient unsuitable for lung transplantation . Moreover, education and managing the expectations of patients and their family is essential in the pre-transplant period.
Pulmonary rehabilitation
Pre-transplant exercise training is recommended to optimize fitness and avoid deconditioning caused by inactivity that can occur with advanced lung disease . Evaluation of exercise capacity, muscle function, mobility, activities of daily living and physical activity is essential. High-intensity interval training and inspiratory muscle training protocols along with optimal home oxygen support can be provided to the individual patient .
Dietetics advice
Malnutrition adversely affects outcomes in lung transplantation. Recipients with BMI <20 or <80% of predicted body weight have a reduced survival following transplantation . There is little evidence on an appropriate clinical measure of malnutrition, but the newly developed muscle index may be a prognostic factor in lung transplantation . In many recipients, especially CF patients, maintaining nearly normal body weight and disease tailored nutrition is overseen by trained dieticians.
Infection control
Potential sites of infection such as nasal sinus, teeth or intravenous catheters should be investigated and treated. Appropriate vaccinations should be administered before transplantation.
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