Article Category: General Reviews
Pubblicato online: 27 lug 2020
Pagine: 3 - 10
DOI: https://doi.org/10.2478/pneum-2020-0001
Parole chiave
© 2020 Irina Pele et al., published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
A simple dictionary definition of
Most of the patients undergoing thoracic surgery suffer from lung cancer (10) and its associated comorbidities. They often have a multifactorial limitation of their exercise capacity due to ventilatory, cardiovascular, musculoskeletal or psychological disorders (9,11). This is one of the reasons why international guidelines state that functional capacity assessments are essential for preoperative evaluation (9,10). The peak/maximal exercise capacity evaluation through cardiopulmonary exercise test (CPET) can help in assessing perioperative risks, influences the type of intervention performed and helps to improve organ dysfunctions in the preoperative period (12,13). Although several fields and laboratory exercise tests are currently accepted in assessing exercise performance, the CPET represents the “gold standard” (14,15).
This article aims to provide a summary overview of CPET. We will address, in particular, its roles in the preoperative evaluation, prognosis of morbidity and mortality, postoperative assessment and pulmonary rehabilitation of thoracic surgery patients.
CPET is a dynamic test that evaluates the respiratory, cardiac, circulatory, metabolic and muscular functions, under standardised and controlled physiological conditions (14,15). The body's integrated response to exercise is evaluated through direct measurement of respiratory gas exchange and pulmonary ventilation, using the “breath-by-breath” method, which involves the use of a sealed oronasal mask. The electrocardiogram, blood pressure, heart rate and arterial oxygen saturation (pulse oximetry) are recorded as well (14,15,16,17; Figure 1).
Figure 1
Cardiopulmonary exercise test on the cycle ergometer.
The CPET methodology requires specialised equipment for measuring breathing and cardiovascular parameters (an
A synthesis on the utility of the data provided by the CPET in surgical patients, as it was underlined, in several systematic reviews on this subject, is presented below:
CPET objectively appreciates the patient's physical fitness and identifies the cause of exercise intolerance; when the exercise capacity is decreased, it can identify the limiting factors (respiratory, cardiac, neuromuscular, etc.) (15,17); CPET can guide the preoperative management decision: to cancel or to postpone surgery, to guide the choice of surgical procedure (limited or extended surgical resection) or oncology treatment (19,20,21); CPET can facilitate the identification of underlying comorbidities and thus provides the possibility to optimise patient's treatment (e.g. heart failure, ischaemic cardiac disease and pulmonary hypertension) (15,16,17, 20,21,22); CPET estimates the risk of adverse events (morbidity or mortality) of the patient (19,20,22,23); CPET guides anaesthesia procedures and immediate postoperative care level needed, thereby reducing postoperative morbidity (20,22); CPET assesses the patient's functional capacity after surgery, providing information on the required mode and length of recovery after lung resections (19); CPET assists with tailoring an individualised pulmonary rehabilitation programme, in the pre and/or postoperative period (19,20,22); CPET allows assessing the effects of oncologic therapy (neoadjuvant chemo- or chemo-radiotherapy) in lung cancer (20).
As part of the preoperative assessment of thoracic surgery patients, the need for the functional capacity evaluation is highly evident in the medical literature and primarily concerns patients with lung cancer (23,24,25,26,27). Thus, over the period 2003 to 2013, experts from American and European Respiratory and Thoracic Surgeons Societies published a series of evidence-based guidelines for the diagnosis and stratification of high-risk patients with lung cancer (23,24,25,26,27).
From our point of view, the method may also be useful in patients who need surgical treatment due to other pulmonary diseases—benign tumours, localised lung infections (abscess, aspergilloma and tuberculoma) and infected bronchiectasis. Thus, physicians will be able to classify the patients with increased risk of complications and assess the impact of the intervention on lung function and quality of life. The decision for surgery is all the more complex as patients get older and have associated comorbidities, and secondary mortality is still a burden of health (20,22,28,29).
The subject's cardiovascular status and lung function dictate the need for preoperative CPET. After completing the test, the physicians can decide whether the patient is “fit for surgery” (20) or not. Over the years, guideline recommendations regarding patient selection varied but were all based on the following parameters: the forced expiratory volume in one second (FEV1), diffusing capacity of the lung for carbon monoxide (DLCO) and their predicted postoperative (PPO) values (Figure 2). The 3rd edition of the American College of Chest Physician (ACCP) guideline, the newest published guideline on this subject (2013), recommends performing preoperative CPET in patients with lung cancer with ppoFEV1 and/or ppoDLCO below 30% predicted (28).
Figure 2
The place of CPET in guidelines recommendation according to FEV1, DLCO and their PPO values. ACCP, American College of Chest Physician; BTS, British Thoracic Society; CPET, cardio-pulmonary exercise test; DLCO, diffusing capacity of the lung for carbon monoxide; ERS/ESTS, European Respiratory Society/European Society of Thoracic Surgeons; FEV1, forced expiratory volume in 1 second; PPO, predicted postoperative.
Predicted postoperative lung function (ppoFEV1 and ppoDLCO) may be calculated by estimating the amount of unobstructed lung tissue that would be resected (25,26,27,28). The methods used may include anatomic formulas involving bronchopulmonary segments to be removed, ventilation and/or perfusion scan, quantitative CT scan and oxygen-enhanced MRI (25). The anatomic method is often applied to estimate lung function after lobectomy, whereas the radionuclide perfusion scan is preferred for pneumonectomy (25,26,27,28).
Studies regarding the utility of the CPET in identifying patients with high risk of postoperative complications are numerous, and many of them dedicated to non-cardiothoracic surgery (23). Some variables of the CPET have been proven useful as significant predictors of morbidity and mortality: peak oxygen consumption (VO2peak), anaerobic threshold (AT) and ventilatory equivalent for carbon dioxide (VE/VCO2 slope) (19,20,22,23).
VO2peak and AT are the measures of subject's exercise capacity and are expressed in millilitres of O2 uptake per minute (ml/min), millilitres of O2 uptake per minute and per kilogramme of body weight (ml/min/kg) or as a percentage of their predicted values (22). The gas exchange efficiency is assessed by the
Parameters of the CPET with threshold values and their postoperative outcome
| Bechard et al. 1987 ( | <10 ml/kg/min | 29% mortality and 43% morbidity (10.7% morbidity if 10 < VO2 max < 20 ml/kg/min; no mortality/morbidity if VO2 >20 ml/kg/min) | |
| Brunelli et al. 2009 ( | <12 ml/kg/min | 13% mortality and 33% morbidity (no mortality, 3.5% morbidity if VO2 >20 ml/kg/min) | |
| Smith et al. 1984 ( | <15 ml/kg/min | 100% morbidity | |
| Byram et al. 2007 ( | 39% morbidity (no morbidity if VO2 ≥ 15 ml/kg/min) | ||
| Bolliger et al. 1995 ( | <60% | 85.5% probability of complications after resection involving more than one lobe | |
| <43% | 90% probability of serious complications | ||
| Larsen et al. 1997 ( | <50% | 60% sensitivity of mortality risk | |
| Guazzi et al. 2016 (39) | <11 ml/kg/min | High risk of complications (proposed prognostic marker) | |
| Torchio et al. 2010 ( | ≥34 | 5.5% of patients predicted not to survive after surgery (98% of patients predicted to survive if VE/VCO2 <34) | |
| The only independent mortality predictor | |||
| Brunelli et al. 2012 ( | >35 | High risk of respiratory complications (22% vs. 7.6%) and mortality (7.2% vs. 0.6%); comparison with patients with VE/VO2 ≤35 | |
| Miyazaki et al. 2018 ( | >40 | 90-day mortality: 16% vs. 5% | |
| 2-year mortality: no difference (comparison with patients with VE/VCO2 ≤40) |
AT, anaerobic threshold; CPET, cardiopulmonary exercise test; VE/VCO2 slope, the ventilatory equivalent for CO2 slope; VO2peak/max, peak/maximum oxygen uptake; n, number of patients.
VO2peak is the highest value of oxygen uptake measured during CPET, at the end of the incremental exercise phase, and it is the most used parameter describing the subject's functional capacity in surgery candidates (14,15,16). When the oxygen uptake reaches a physiological end-point,
Over the years, there were controversies about the best thresholds which separate the lower risk from the intermediary/high risk for complications after lung resections. For this purpose, most cohort studies use absolute values indexed to body weight instead of the percentage of the predicted value. Such cut-off points of VO2 for higher risk of postoperative adverse events were 10, 12 and 15 ml/kg/min, respectively (30,31,32,33,34).
On the other hand, some studies have shown a better discriminatory ability of oxygen consumption expressed as a percentage of the predicted value. The mentioned cut-off points of risk are in descending order from 60% to 40% predicted (34,35,36). However, using only absolute values can underestimate the real physical fitness of patients in clinical practice, with particular implications for certain categories of persons such as the elderly, the obese and subjects of short height (5).
It is now certain that patients with values >20 ml/kg/min (or 75% predicted) can undergo major interventions such as pneumonectomy. While in patients with values <10 ml/kg/min (or 35% predicted), oncological or palliative treatments are preferable (28).
AT or the lactate threshold is a measure of the submaximal exercise capacity. It is the oxygen consumption (VO2) achieved almost entirely under aerobic conditions when the lactic acid serum level starts to increase (reflecting anaerobic glycolysis) with metabolic acidosis (14,15,16,22). Unlike VO2peak, it is a non-volitional variable and reflects an increase in the contribution of anaerobic metabolism to aerobic one in the presence of restricted oxygen supply (22). It is a predictor of postoperative morbidity and mortality for major elective surgery (especially intra-abdominal surgical procedures) (22,23,37) and cardiovascular diseases (myocardial ischaemia and heart failure) (38), with a threshold value for high risk ranging from 9 to 11 ml/kg/min (22,23,37,38). The absolute value of VO2 at AT indexed to bodyweight seems to be the best predictor of postoperative complications (22,23). The literature is poor in evidence-based data about AT in thoracic surgery.
Guazzi et al. (39) proposed a CPET-based algorithm for presurgical risk assessment, which includes VO2 at AT. An AT <11 ml/kg/min is considered to be a prognostic marker of high risk for complications, especially when it is associated with a low VO2peak and high VE/VCO2 values (39).
The ratio of the minute ventilation to CO2 output is the expression of gas exchange efficiency, whose prognostic value has started to emerge in recent years (40,41,42,43,44). Similar to the AT, VE/VCO2 is a variable measured at the submaximal workload (16,19,22).
Increased values of ventilatory equivalents were described in several diseases, such as heart failure (45), pulmonary hypertension (46) or pulmonary fibrosis (47), emphasising a poor prognosis. The parameter was also analysed in clinical studies of surgery candidates, including thoracic surgery patients, and it was suggested that it could be even a better predictor of respiratory morbidity and mortality compared with VO2max (40,41,43). Again, the threshold risk values used in the triage of patients are different between studies. These values vary from 34 to 40 (40,41,42,43,44). Moreover, current studies develop the idea that VE/VCO2 could be a significant predictor of short- and long-term survival (42,44).
All these differences between studies could be explained by the progress of health systems, with improved patient screening, surgical and care technique or a variety in the number and/or origin of the population samples. However, the optimal predicted parameters and their risk delimitation threshold in thoracic surgery remain controversial at present, requiring more extensive studies (20,22).
Although CPET is not among the routinely performed tests in the postoperative period, there are a few studies that analysed the effect of lung resection on exercise capacity (19,48).
Ha et al. described nine studies in their meta-analysis on patients with lung cancer performing CPET (19). Those studies showed the dynamics of lung function after partial or total lung resections at various intervals 3, 6 and 12 months. The majority of patients who underwent lobectomy had a recovery of exercise tolerance within 3 month after surgery (19). As expected, due to a broader limitation of the functional reserve, patients who underwent pneumonectomies have a slower recovery or do not recover at all even after >6 months from the surgery (49).
The influence of pulmonary resections on the results of lung function tests and exercise capacity is noteworthy. Longitudinal studies measuring respiratory parameters after lung resections showed discrepancies between the pulmonary function recovery and the recovery of exercise capacity (50,51). Caution is mandatory during preoperative assessments in order not to underestimate the functional status by limiting evaluations only to lung function test evidence (50,51).
Physical training induces an adaptive response of the whole body, and it is the best way to increase effort capacity in anticipation of future physiological stress (12,18,20). During surgery, both the physiological challenge of the intervention itself and the anaesthesia induce stress (20).
Reports from the studies in recent years suggest that based on CPET parameters, the physician can prescribe the physical training necessary in pulmonary rehabilitation programmes and can also asses their effectiveness (19,52). A feasible and effective pulmonary rehabilitation programme can increase the AT and VO2peak, minimising the negative impact of surgical stress on cardiopulmonary and metabolic functions (12,20). Systematic reviews described the effect of preoperative physical training in reducing the number of postoperative complications, the length of hospital stays and in improving the quality of life in patients with lung cancer (53,54).
Currently, for patients undergoing thoracic surgery, short-term high-intensity interval training (HIIT) regimes can be an option (20,55,56). Symptom limited-CPET is performed first, with the determination of VO2peak and peak work rate (WRpeak)—the highest exercise level maintained for about 20 s (56). The patients must repeat the test after 3 or 4 weeks of training. A significant change (>10%) in VO2peak defines a positive response to rehabilitation (55).
The design of a HIIT programme is shown in Figure 3 by using adapted data previously published (55,56). Participants usually exercise on a cycle ergometer 2–3 times a week under the supervision of a physiotherapist (55,56). The work rate is adjusted to obtain near maximal heart rates towards the end of the sprint interval (56).
Figure 3
Design of a HIIT programme (adapted from published data) (55,56). HIIT, high-intensity interval training; WRpeak, peak work rate.
The HIIT programme individualised by measured CPET variables resulted in a meaningful improvement in cardiorespiratory fitness compared with usual care (20,22,55,56).
In the postoperative period, a pulmonary rehabilitation programme can also improve the quality of life, minimising symptoms like breathlessness. Kim et al. (57) demonstrated the benefits of a 6-month systemic pulmonary rehabilitation programme after lung resection surgery in their study. The patient exercised at least three times a day for 20 min. The sessions focussed on chest expansion exercises, segmental breathing, respiratory muscle training and breathing control training (57). Training exercises helped to enhance performance status and prevent the postoperative decline of lung function parameters (57).
Supervised long-term postoperative training and patients’ educational and counselling programmes regarding physical activity are needed to maintain a better functional and clinical outcome (56,57).
Information provided by the CPET is complex. It can be used in thoracic surgery to assess the potential risk of morbidity and mortality, define particular patient profiles and make subsequent therapeutic decisions, including choosing a pulmonary rehabilitation programme.