Assessment of suitability for lung resection

Gerard Gould FRCA Adrian Pearce FRCA

Approximately 2400 lobectomies and 500 pneumonectomies are undertaken in the UK annually, the majority for malignancy. For this group of patients, in-hospital mortality rates are 24% and 68%, respectively in the UK, although world mortality rates as high as 11% have been cited for pneumonectomy. For lung cancer surgery, there are three prerequisites before pulmonary resection is even considered. The tumour type should be nonsmall cell (the majority are squamous cell or adenocarcinoma), the tumour is considered surgically resectable and the patient consents to surgery. Surgical resectability depends on the absence of significant mediastinal or distant spread as judged by computerised tomography (CT), positron emission tomography (PET), bronchoscopy or mediastinoscopy. Guidelines1 on the selection of patients with lung cancer for surgery, published by a joint working party of the British Thoracic Society (BTS) and Society of Cardiothoracic Surgeons of Great Britain and Ireland advise that fitness for surgery is based on assessment of age, cardiovascular fitness, nutrition and performance status and respiratory function. Perioperative morbidity increases with age; a careful assessment of co-morbidity should be made in elderly patients. However, age alone is not a contraindication to lobectomy or wedge resection in early disease, although it is a factor to be considered before undertaking pneumonectomy. Weight loss >10%, a low BMI or serum albumin may indicate more advanced disease or an increased risk of postoperative complications. Recommendations appropriate to the cardiovascular system are summarized in Table 1. The guidelines2 from the American College of Cardiology and the American Heart Association should be used to stratify perioperative cardiovascular risk. Those at major risk (Table 2) should undergo a cardiology assessment and be considered for coronary angiography. Generally, patients in intermediate and minor risk categories should be assessed for functional capacity and continue with surgery.

Table 1 Cardiovascular recommendations before lung resection Cardiac risk should be stratified All patients should have a preoperative ECG All patients with a cardiac murmur should undergo echocardiography Patients should wait 6 weeks after myocardial infarction before lung resection A cardiology opinion should be sought for all patients considered for lung surgery within 6 months of myocardial infarction

Key points Co-morbidity is common in patients with lung cancer. A preoperative FEV1 of >1.5 litre for lobectomy and >2.0 litre for pneumonectomy generally indicates suitability. Values less than this should prompt further investigation of respiratory function. A thorough assessment of cardiorespiratory reserve includes calculation of predicted postoperative pulmonary function. CPET should be available in centres providing a thoracic surgical service. A multidisciplinary approach is essential and should include anaesthetist, chest physician, thoracic surgeon and radiologist.
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Table 2 Major risk factors for increased perioperative cardiac morbidity Unstable coronary syndromes  acute or recent myocordial infarction (MI) with evidence of important ischaemic risk by clinical symptoms or noninvasive study  unstable or severe angina Decompensated heart failure Significant arrhythmia  high-grade atrioventricular block  symptomatic ventricular arrhythmias in the presence of underlying heart disease  supraventricular arrhythmias with uncontrolled ventricular rate Severe valvular disease

Tests of pulmonary function

Lung function tests pre-surgery
Basic spirometry will measure the forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) and the best value after optimal bronchodilator therapy is used. The measured value in litres may also be compared with the predicted value for a normal person derived from population studies and varying with age, gender, race and height, giving a percentage of the predicted normal value. The ratio of FEV1/FVC is commonly determined. More sophisticated testing allows measurement of the peak, mid- and end-expiratory flow rates and residual volume. Flow-volume loops may be constructed in which flow rates during inspiration and expiration are recorded continuously from residual volume to vital capacity and back to residual volume. Diffusion capacity is calculated by measurement of the amount of carbon monoxide

Gerard Gould FRCA SpR 5 Thoracic Anaesthesia Guys and St Thomas Hospital London Adrian Pearce FRCA Consultant Anaesthetist Department of Anaesthesia Guys and St Thomas Hospital London SE1 9RT UK Tel: 020 7188 0644 Fax: 020 8468 7466 E-mail: adrian.pearce@gstt.nhs.uk (for correspondence)

doi:10.1093/bjaceaccp/mkl016 Continuing Education in Anaesthesia, Critical Care & Pain | Volume 6 Number 3 2006 The Board of Management and Trustees of the British Journal of Anaesthesia [2006]. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

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(CO) taken up by the patient in unit time (DLCO). The units are amount of CO per unit of alveolar concentration per unit timemmol kPa1 min1. The test provides a gross estimate of alveolar/capillary function and is not (as commonly supposed) just a test of the diffusion of oxygen across the alveolar capillary membrane. The diffusion capacity may be referenced to alveolar volume (transfer coefficient, KCO) with units mmol kPa1 min1 litre1. Both DLCO and KCO may be described as the actual value or as a percentage of the predicted normal values for a particular patient.

Exercise capability
Exercise testing stresses the cardiopulmonary and oxygen delivery systems and provides a good indication of cardiopulmonary reserve. The simplest test assesses the number of flights of stairs that may be climbed without stopping. This may be undertaken in the outpatient department or ward and is a good screening test. Two more standardized tests may be used. The 6-min walk involves walking as far as possible in 6 min. The test should be performed indoors along a long, flat, straight, enclosed corridor. Most studies quote a course of 30 m in length with cones at either end to act as turnaround points. Rest is allowed during the test. In the shuttle walk test, the patient walks back and forth around two markers at increasing speed timed by an audible signal. The markers are usually cones with their centres 9 m apart making the course 10 m in length. The subject aims to walk around the 10 m course and turn around the first marker cone when the first audio signal is given, and so on. Progression to the next level of difficulty is indicated by a triple bleep which lets the subject know that an increase in walking speed is required. The test stops when the patient is too breathless to maintain the speed required or after 12 min, and the number of cones reached is recorded.

Predicted postoperative respiratory function

The predicted or estimated postoperative (ppo or epo) values of FEV1, FVC and diffusion capacity can be obtained by consideration of the lung volume removed at surgery. For lobectomy, the simple calculation uses the number of bronchopulmonary segments removed compared with the total number (19) in both lungs. For right upper lobectomy (3 segments) in a patient with a preoperative FEV1 of 1.6 litre which is 80% of predicted normal, the ppo-FEV will be 1.616/19 1.35 litre, and the ppo-FEV1% will be 80%16/19 67%. The same form of ppo calculation may be applied to the measured DLCO or the DLCO as a percentage of the predicted normal value. Of course, this gross calculation assumes that all bronchopulmonary segments contribute equally to the overall lung function and this may not be so. Ventilation scans will provide a more accurate calculation of ppo lung volumes.

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Cardiopulmonary exercise testing

Formal testing of cardiopulmonary exercise capability appears to give the most accurate indication of postoperative complications. Cardiopulmonary exercise testing (CPET) is a non-invasive technique that involves submaximal and maximal treadmill or bicycle exercise (Fig. 1) with continuous ECG monitoring and breath-by-breath determination of oxygen uptake and carbon dioxide output, and spirometry. Maximal oxygen consumption _ O2 max), peak heart rate, exercise capacity, anaerobic thresh(V _ O2 old and respiratory gas exchange ratio can be calculated. V max is the highest oxygen consumption achieved at maximal work before stopping the test (Fig. 2), and is usually given in _ O2 max for a the units ml kg1 min1. The predicted normal V _ O2 patient may be derived from charts, allowing derivation of V _ O2 max predicted). max as a % of predicted normal (% V

Ventilation/perfusion scanning
Quantitative ventilationperfusion scanning calculates the percentage function of each lung. This is achieved by the inhalation of radioactive xenon and the i.v. administration of technetium labelled macroaggregates. A gamma camera and computer calculate the uptake of radioactive ions by the lung or the perfusion of technetium. The percentage of radioactivity taken up by each lung correlates with the contribution of that lung to overall function. Using the measured radioactive uptake of the lung that will not be operated on, the predicted FEV1 of the residual lung after pneumonectomy can be calculated by the following simple equation: Postop FEV1 Preop FEV1 % radioactivity of non-operated lung A further calculation has been developed for predicting postlobectomy pulmonary function using V/Q scanning. Expected loss of function pre-op FEV1 % function of affected lung number of segments in lobe to be resected total number of segments in whole lung

Arterial blood gases

Arterial PaCO2 > 6 kPa (45 mm Hg) does not appear to be an independent predictor of poor outcome but preoperative hypoxaemia, oxygen saturations <90% and desaturation >4% with exercise have all been associated with an increased risk of complications.

Predictive power of preoperative tests

Data in >2000 patients from the 1970s indicate that a low mortality can be achieved if the preoperative FEV1 is >1.5 litre

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2.5

1.5

VO2 0.5 VCO2

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0 00:00

02:24

04:48

07:12

09:36

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Fig. 2 Oxygen consumption plotted against increasing work. The _ O2 max is the highest oxygen consumption (ml kg1 min1) at V maximal work.

Fig. 1 Patient undergoing CPET.

for lobectomy and >2 litre for pneumonectomy. Using absolute FEV1 values may be inappropriate in elderly, female or patients of short stature. An FEV1 >80% predicted indicates suitability for pneumonectomy. The relevance of DLCO was suggested in 1988 in a retrospective study 3 in 237 patients. The preoperative DLCO, expressed as % predicted, had a higher correlation with postoperative deaths than FEV1 measurements. A DLCO <60% predicted was associated with increased mortality and <80% predicted with increased pulmonary complications. In a prospective study,4 67 patients with preoperative FEV1 >80% and DLCO >80% and no cardiac history underwent lung resection, including pneumonectomy, without death. The ppo values of FEV1 and DLCO may be used and generally a threshold ppo-FEV1 of 0.70.8 litre is advisable after lung resection. The ppo value of FEV1 or DLCO as a percentage of the predicted normal value appears to be particularly valuable. Several studies indicate that mortality increases when ppo-FEV1 or ppo-DLCO is <40% predicted. The product of ppo-FEV1% and ppo-DLCO% may be useful and a threshold of 1650 has been used. There are few prospective studies evaluating outcome in patients with ppo-FEV1 or DLCO <40% but in one study5 of 65 patients with poor lung function and undergoing either lobectomy or pneumonectomy the mortality rate was only 6.2%.

Historically patients were considered suitable for lobectomy if able to climb three flights of stairs and for pneumonectomy if able to climb five flights. This was found to correlate with lung function, three flights indicating an FEV1 >1.7 litre and five flights an FEV1 > 2 litre. Limited work suggests that _ O2 max patients who can climb five flights of stairs have a V 1 1 >20 ml kg min and those unable to climb one flight one of <10 ml kg1 min1. An inability to complete 25 shuttles _ O2 max (250 m) in 5 min on two occasions suggests a V 1 1 <10 ml kg min and a high risk for surgery. _ O2 max was indicated by a study of 19 The usefulness of V _ O2 max >1 litre min1 survived patients in 1982. Patients with a V 1 and those < 1 litre min died. Numerous further studies indicate _ O2 max may be used to stratify risk of postoperative comthat V _ O2 max >20 ml kg1 min1 indicates plications and mortality. V no increased risk of complications or death, <15 ml kg1 min1 indicates an increased risk of complications and < 10 ml kg1 min1 indicates mortality rates of 4050%. Satisfactory VO2 max may allow selection of patients deemed unsuitable by lung volume measurements. In 37 patients6 with poor respiratory function (FEV1 <40%, ppo-FEV1 <33% or PaCO2 >6 kPa), 8 patients with VO2 max >15 ml kg1 min1 survived lobectomy. _ O2 max % predicted has been The use of the preoperative V 7 _ O2 max % analysed. In 80 patients undergoing lung resection, V _ _ O2 max % predicted was more sensitive than absolute VO2 max. V predicted >75% indicated a low risk of complications, <43% a

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Assessment of suitability for lung resection

Routine Lung Function Tests

FEV1 > 1.5 litre suitable for lobectomy FEV1 > 2.0 litre suitable for pneumonectomy

FEV1 < 1.5 litre (Lobectomy) < 2.0 litre (pneumonectomy)

SURGERY

Quantitative Lung Scan

% ppo FEV1 > 40% % ppo TLCO> 40%

% ppo FEV1 < 40% % ppo TLCO< 40%

Exercise Testing

VO2 max > 15ml kg1 min1

VO2 max < 15ml kg1 min1

Consider other options

Fig. 3 Preoperative evaluation before lung resection.

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high risk of complications and <60% appeared to be the threshold value for resections of more than one lobe. A number of studies support the finding that patients with _ O2 max of >20 ml kg1 min1 are not at a preoperative V _ O2 increased risk of complications or death and those with a V max <10 ml kg1 min1 have a very high risk for postoperative complications. If CPET is unavailable then other less sophisticated tests can be used.

References
1. British Thoracic Society and Society of Cardiothoracic Surgeons of Great Britain and Ireland Working Party. Guidelines on the selection of patients with lung cancer for surgery. Thorax 2001; 56: 89108 2. Eagle KA, Berger PB, Calkins H, et al. ACC/AHA guideline update for perioperative cardiovascular evaluation for noncardiac surgery 2002. Available from http://www.acc.org/clinical/guidelines/perio/update/ periupdate_index.htm. 3. Ferguson MK, Little L, Rizzo L, et al. Diffusing capacity predicts morbidity and mortality after pulmonary resection. J Thorac Cardiovasc Surg 1988; 96: 894900 4. Wyser C, Stulz P, Soler M, et al. Prospective evaluation of an algorithm for the functional assessment of lung resection candidates. Am J Respir Crit Care Med 1999; 159: 14506 5. Ribas J, Diaz O, Barbera JA, et al. Invasive exercise testing in the evaluation of patients at high risk for lung resection. Eur Respir J 1998; 12: 142935 6. Morice RC, Peters EJ, Ryan MB, et al. Exercise testing in the evaluation of patients at high risk for complications from lung resection. Chest 1992; 101: 35661 7. Bolliger CT, Jordan P, Soler M, et al. Exercise capacity as a predictor of postoperative complications in lung resection candidates. Am J Respir Crit Care Med 1995; 151: 147280 8. Beckles MA, Spiro SG, Colice GL, Rudd RM. The physiologic evaluation of patients with lung cancer being considered for resectional surgery. Chest 2003; 123: 105S14S 9. Datta D, Lahiri B. Preoperative evaluation of patients undergoing lung resection surgery. Chest 2003; 123: 2096103

Algorithms
Both the BTS and American College of Chest Physicians (ACCP)8 9 have produced management algorithms which are similar. The flow chart shown in Figure 3 is an amalgamation of the BTS and ACCP guidelines. The initial screening tool is of preoperative measured FEV1 with >2 litre required for pneumonectomy and >1.5 litre for lobectomy. If there is no diffuse lung disease and no comorbidity, achievement of the appropriate lung volume is sufficient. When these threshold lung volumes are not present, full respiratory function testing allows calculation of the predicted postoperative FEV1 and DLCO. If both are >40% and the oxygen saturation is >90% on air the patient is in an average risk group. If either (or both) the predicted postoperative FEV1 or DLCO are <40%, the patient should undergo formal CPET, if necessary through referral to a unit with this expertise. _ O2 max of 15 ml kg1 min1 delineates between The threshold V high and medium risk patients.

Please see multiple choice questions 15.

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