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Table of Contents
REVIEW ARTICLE
Year : 2020  |  Volume : 3  |  Issue : 4  |  Page : 760-766

Integrating cardiopulmonary exercise testing and 6-min walk test for predicting postoperative cardiopulmonary complications in patients undergoing lung cancer surgery: A narrative review


Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy

Date of Submission17-Jul-2020
Date of Decision30-Aug-2020
Date of Acceptance05-Oct-2020
Date of Web Publication25-Dec-2020

Correspondence Address:
Chidiebere Emmanuel Okechukwu
Department of Public Health and Infectious Diseases, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome
Italy
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/CRST.CRST_245_20

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  Abstract 


Cardiopulmonary exercise testing (CPET) is an effective method for the assessment of cardiopulmonary and neuromuscular reaction to physical stress. It offers an independent assessment of cardiopulmonary fitness and functional capacity in patients undergoing lung cancer surgery. The 6-min walk test (6MWT) can be used for the assessment of functional capacity when CPET is unavailable. Through this review, we aim to emphasize the importance of utilizing both CPET and 6MWT in the assessment of cardiorespiratory fitness/functional capacity in patients with lung cancer undergoing major thoracic oncological resections. We searched the PubMed electronic database using the MeSH system for articles reporting the use of CPET and 6MWT in cardiopulmonary fitness/functional capacity evaluation during cancer treatment. The full-text articles were assessed, and significant evidence was extracted. Only the articles written in the English language were selected. Using a combination of CPET and 6MWT for the assessment of cardiopulmonary fitness/functional capacity in patients with lung cancer undergoing complex oncological resections, could give a definite prediction of the possibility of postoperative cardiopulmonary complications in these patients.

Keywords: 6-min walk test, cardiopulmonary exercise testing, lung cancer, preoperative evaluation, surgical outcome


How to cite this article:
Okechukwu CE. Integrating cardiopulmonary exercise testing and 6-min walk test for predicting postoperative cardiopulmonary complications in patients undergoing lung cancer surgery: A narrative review. Cancer Res Stat Treat 2020;3:760-6

How to cite this URL:
Okechukwu CE. Integrating cardiopulmonary exercise testing and 6-min walk test for predicting postoperative cardiopulmonary complications in patients undergoing lung cancer surgery: A narrative review. Cancer Res Stat Treat [serial online] 2020 [cited 2021 Jan 21];3:760-6. Available from: https://www.crstonline.com/text.asp?2020/3/4/760/304952




  Introduction Top


Predicting the postoperative cardiopulmonary complications (PCCs), setting up measures to reduce the postoperative risk, and to improve the recovery after lung cancer surgery are the major reasons for assessing the preoperative cardiopulmonary fitness. The preoperative peak oxygen uptake (VO2peak) is essential to determine the risk of PCC. It provides the opportunity to develop exercise regimens that can increase VO2peak before surgery. This in turn may reduce the PCC and increase the postoperative recovery in patients with lung cancer who undergo major thoracic oncological resections.[1] However, cardiopulmonary exercise testing (CPET) and the 6-min walk test (6MWT) are used as prognostic techniques to determine cardiopulmonary fitness and functional capacity in patients with lung cancer who undergo major thoracic oncological resections. Jones et al.[1] utilized both CEPT and 6MWT to ascertain the impact of preoperative training on the cardiopulmonary fitness of such patients and obtained definite results regarding the patients' preoperative fitness.

The aim of this narrative review is to emphasize the importance of utilizing both CPET and 6MWT in the assessment of cardiorespiratory fitness/functional capacity in patients with lung cancer who undergo major thoracic surgeries. The outcomes from both the assessments could better predict the PCC in patients with lung cancer.


  Methods Top


Search strategy

Articles reporting the use of CPET and 6MWT in cardiopulmonary fitness/functional capacity evaluation during cancer treatment published between 1999 and 2020 were searched for using the PubMed electronic database. Relevant articles were selected, full-text articles were assessed, and significant evidence was extracted. The MeSH system was used to obtain the relevant research studies from the PubMed database using the following search terms: “CPET,” “6MWT,” “lung cancer,” and “preoperative evaluation.”

Types of selected studies

Original articles, consensus clinical guidelines, systematic reviews, and meta-analyses were selected for further assessment.

Inclusion and exclusion criteria

Only the articles that discussed the role of CPET and 6MWT in the assessment of cardiorespiratory fitness, especially in patients with lung cancer who were undergoing major thoracic oncological resections were included in this review. The articles written in the English language were selected. Articles that were not detailed or were ambiguous with questionable procedures were excluded. A total of 19 studies were included in this narrative review.

Data extraction and management

All the articles retrieved from the PubMed database were classified based on their relevance, based on whether they reported the use of CPET and 6MWT in cardiopulmonary fitness/functional capacity evaluation during or before lung cancer surgery. The full-text versions of all the articles identified as relevant to this review were retrieved. The data were reported in a concise manner. The selection process for articles is explained with the help of a Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) flow diagram [Figure 1].
Figure 1: Preferred Reporting Items for Systematic Reviews and Meta Analyses flow diagram for selection of articles regarding cardiopulmonary exercise testing and 6-min walk test

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  Discussion Top


Cardiopulmonary exercise testing

CPET is an effective technique used in the assessment of cardiopulmonary and neuromuscular response to physical stress, and it offers an independent measurement of cardiorespiratory fitness/functional capacity in patients undergoing lung cancer surgery.[2] CPET combines the assessment of expired gas with the synchronized inspection of heart rate (HR), arterial blood pressure, oxygen capacity, and electrocardiography.[2] It focusses on progressive clinical exercise testing up to the threshold of tolerance using cycle ergometry and on evaluating the three key indicators of cardiopulmonary fitness which are:

  1. The VO2peak, achieved on a fast-progressive test, quantified in mL/kg/min;
  2. Anaerobic threshold (AT), which is a sub-maximal indicator of exercise level, and is usually quantified in mL/kg/min; and
  3. The ventilatory equal for carbon dioxide (VE/VCO2), which is the relative amount of minute ventilation to carbon dioxide production (the VE/VCO2 slope, which is a strong predicator of mortality).[3]


Patients with lung cancer with VO2peak more than 20 mL/kg/min are considered low-risk for surgical treatment, those with VO2peak of<10 mL/kg/min are considered high-risk for lung cancer surgery, and patients with VO2peak between 10 and 20 mL/kg/min undergo further risk stratification.[3] Moreover, patients with AT<11 mL/kg/min are considered to be at a high risk of postoperative morbidity and mortality.[3] The VO2peak, AT, and VE/VCO2 slope are relevant parameters for preoperative risk stratification. The assessment of functional reserve is exceptionally essential, because a poor cardiopulmonary capacity is indicative of the incapability to deal with the stress caused by surgical procedures, and hence, adds to the development of PCC. The result obtained from CPET is useful for patients' categorization, however, the categorization of patients based on their cardiopulmonary fitness, functional capacity and other health factors which are associated with their ability to withstand surgical resection, does not definitely mean that patients from the same category have identical clinical status, but that they are comparable to each other by specific clinical features in relation to patients from another category. This enables clinicians to determine the actual medical and surgical need of each patient in a particular category. CPET is currently the benchmark technique for the evaluation of cardiopulmonary fitness, as it can measure the training ability and detect the root of physical deconditioning in patients with lung cancer and subsequently predict PCC thereby presenting an opportunity for targeted optimization.[3]

The 6-min walk test

The 6MWT can be used for the assessment of functional capacity when CPET is unavailable. The assessment entails walking on a firm and level surface at a fast pace for 6 min. The individuals select their pace and magnitude of exertion during the assessment, and the last parameter measured is the distance in meters covered by the patient after walking at a fast pace for 6 min. The longer the distance covered, the greater is the patient's functional capacity.[4] The test is usually conducted by mapping out a distance of 30 m using cones and brightly colored tape to mark the boundaries of the path. In addition, this test requires a stopwatch, pulse oximeter, heart rate monitor, sphygmomanometer, and a chair to enable the patient to relax after the test.[4] The 6MWT allows for a unified assessment of the cardiopulmonary function and neuromuscular components. Patients who cover a distance of more than 400 m are deemed to have good functional capacity, while those who cover<400 m are considered to have poor functional capacity.[5] Unlike the CPET, the 6MWT is based on self-pace, wherein the patient chooses the intensity of effort, and hence presents an outcome of sub-maximal effort. Considering that the majority of the daily activities are performed at a sub-maximal level, the 6MWT presents the definite functional status of daily living.[5] The 6MWT can be used to predict PCC, because it provides an opportunity to quantify the patients' internal training load, exercise tolerance, and endurance using the Borg rating of perceived exertion scale.[5]

Postoperative cardiopulmonary complications

PCCs are the major cause of postoperative morbidity, prolonged hospitalization, and mortality in patients after complex lung cancer surgeries. They usually occur within 30 days postoperatively, and are defined as grade II or greater according to the Clavien–Dindo classification.[6] PCCs lead to higher costs of treatment. Cardiopulmonary fitness is a recognized marker for PCC and surgical readiness; a lower cardiopulmonary fitness, is an indicator of PCC and postoperative morbidity and mortality.

Postoperative cardiac complications

These include major cardiac complications such as ventricular fibrillation, pulmonary edema, and myocardial infarction, which is myocardial necrosis marked by a high troponin level.[7] According to Davenport et al.[8] mortality within 30 days from surgery in patients who had an unfavorable cardiac episode, is defined as myocardial infarction with ST-segment elevation. Myocardial impairment after non-cardiac surgery usually occurs within 30 days from surgery.[9]

Postoperative pulmonary complications

Postoperative pulmonary complications were defined by Kaufmann et al.,[10] as the need for intensive ventilation because of hypercapnia or hypoxia, the need for intubation because of hypercapnia/hypoxia, persistent air leak for ≥5 days after surgery, thoracic drainage owing to raised pleural discharge, and pleural empyema. Pulmonary complications consist of a large array of respiratory diseases, including acute respiratory failure, pneumonia, atelectasis, and the necessity for sustained mechanical ventilation.[11] The kind of pulmonary problems and the occurrence of these impediments differ, depending on the kind of surgical treatment conducted. However, irrespective of the kind of surgical treatment that a patient receives, postoperative pulmonary complications delay recovery and prolong hospitalization.[11]

Exercise prescription for the improvement of cardiopulmonary fitness to minimize postoperative cardiopulmonary complications and improve postoperative recovery in patients with lung cancer who undergo major oncological resections

High-intensity interval training (HIIT) is an effective therapeutic exercise used to improve cardiorespiratory fitness and the quality of life in patients with cancer who undergo major oncological resections. This exercise regimen is majorly individualized and supervised with regard to the patients' current physical health, health history, tolerance, preference, and overall clinical status [Figure 2].[12] Major contraindications to exercise are the presence of severe cardiopulmonary diseases, lymphedema, severe fatigue/exhaustion, and acute anemia. A short-term HIIT intervention is usually conducted to improve the preoperative physiological reserves and to increase the postoperative recovery.[13] These tests are usually conducted and supervised by an experienced physiotherapist and an accredited clinical exercise physiologist, mostly in collaboration with a cardio-oncologist in order to maintain safety and in accordance with global best practices. Bhatia et al.,[14] conducted a short-term HIIT program for physically deconditioned patients with lung cancer, who were assessed with CPET prior to training. The HIIT involved performing a 10-min series of cycling at peak power twice, with a 15 second on/off burden cycle, preceded by a 5-min warm up and followed by a 5-min cool down, 2–3 times/week.[14] The work-rate, heart-rate, saturation, dyspnea, and leg effort were monitored.[14] However, in order to obtain definitive knowledge about the cardiorespiratory fitness level/functional capacity in these patients, they performed the CPET and 6MWT before and after the HIIT program.[14] Furthermore, at the end of the short-term HIIT program, they observed improvements in the levels of cardiopulmonary fitness and functional capacity among the patients.[14]
Figure 2: High-intensity interval training (HIIT). Grey bars indicate highintensity intervals at 90% peak power output and black bars indicate the 2-min active rest interval at 10% peak power output (Copyright © CC BY-NC 4.0. Lee et al, BMJ Open 2018;8(6): e022622), reprinted with permission

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Additional discussion

Both CPET and 6MWT are important preoperative evaluation techniques that are essential for predicting the likelihood of developing PCC before lung cancer surgery. The outcomes correlate with the patients' physical fitness level, and both tests provide further information that can be used when planning major lung cancer surgeries with regard to the patients' tolerance, endurance, and the possibility of survival. CPET, though complex, is a better test and gives a fair idea about the cardiopulmonary status. A normal VO2 max can rule out any significant abnormality in the skeletal, pulmonary, cardiovascular, and neurophysiological systems. These tests are positioned at different levels during functional evaluation. Usually, CPET is recommended when the results of the patients' pulmonary function test and low-technology exercise tests like stair climbing/shuttle walk or 6MWT are poor. Nevertheless, the combination of CPET and 6MWT for the preoperative evaluation of cardiorespiratory fitness could be more useful in validating and establishing the patients' cardiorespiratory fitness/functional capacity, preoperative fitness, and the rate of postoperative recovery. Based on the preoperative evaluation, patients may be subject to personalized preoperative rehabilitative programs, such as HIIT, which has been found to be effective in improving the cardiopulmonary fitness in patients with non-small cell lung cancer before surgical treatment. Moreover, the optimal fitness level can be maintained after surgery, thus facilitating postoperative recovery.[15] Although HIIT has been shown to improve the preoperative cardiopulmonary fitness, so far studies have not shown a substantial decrease in the postoperative complications in patients who undergo surgical resections, except for a decrease in the postoperative atelectasis and the post-anesthesia care unit stay.

The 6MWT is a moderate-to-vigorous-intensity aerobic exercise, in which about 80% of the maximum HR can be achieved based on the distance covered in the 6-min walk.[16] Silva et al. found a significant association ( P < 0.001) between the 6-min walk distance and VO2peak in CPET, thereby validating the effectiveness of 6MWT [Table 1] and [Figure 3].[16] Furthermore, the comparative study conducted by Miyamoto et al.[17] also proved that the 6MWT was effective in determining the cardiopulmonary fitness and exercise capacity which was validated by CPET in patients with primary pulmonary hypertension. An additional benefit of the 6MWT is that the distance covered in 6 min has a correlation with mortality and survival [Figure 4]. However, according to Lee et al.[18] based on the results of the 6MWT and postoperative outcomes, patients with non-small cell lung cancer at moderate risk who walked a shorter distance had a significantly higher chance of developing PCC than those with a low risk who walked a longer distance. Patients with moderate risk who walked a longer distance better tolerated and endured restorative surgical resections. [Table 2] shows the American College of Chest Physicians Evidence-Based Clinical Practice Guidelines regarding preoperative evaluation, specifically for cardiopulmonary fitness assessment for patients with lung cancer being considered for resection surgery.[19]
Table 1: Intensity of the 6-min walk test with regard to the peak oxygen uptake and heart rate when compared to cardiopulmonary exercise testing (Copyright © CC BY-NC 4.0. Sperandio et al.,[16]), reprinted with permission

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Table 2: Current clinical guidelines for preoperative evaluation, specifically for cardiopulmonary fitness assessment for patients with lung cancer being considered for resection surgery (Source: Diagnosis and Management of Lung Cancer, 3rd ed: Copyright © 2013 American College of Chest Physicians Evidence-Based Clinical Practice Guidelines), with permission

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Figure 3: Significant association (P<0.001) between the 6-min walk distance and VO2peak in cardiopulmonary exercise testing. Copyright © CC BY-NC 4.0. Sperandio et al, Braz J Med Biol Res 2015;48(4):349-353), reprinted with permission

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Figure 4: The Relationship between the distance covered during six-minute walk test (6MWT) and the exercise capacity determined by cardiopulmonary exercise testing (CPET) in patients with primary pulmonary hypertension. Peak VO2: peak exercise oxygen consumption; AT: anaerobic threshold; VE-VCO2 slope: regression slope relating minute ventilation to carbon dioxide output. (Reprinted with permission of the American Thoracic Society. Copyright © 2020 American Thoracic Society. All rights reserved. Miyamoto et al, Am J Respir Crit Care Med 2000;161(2 Pt 1):487-492)

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Future perspectives

There is a need to compare the efficacy of the 6MWT with that of the incremental-shuttle walk test and endurance-shuttle walk test. The results could be validated with CPET outcomes in determining the cardiopulmonary fitness and functional capacity in patients with lung cancer who are recommended to undergo complex surgical resections


  Conclusion Top


The combination of CPET and 6MWT for the assessment of cardiopulmonary fitness and functional capacity in patients with lung cancer who undergo complex oncological resections, could give a clear prediction of the risk of development of PCCs in these patients, thereby creating avenues to increase the cardiopulmonary fitness and health-related outcomes in these patients at the perioperative stage through a short-term HIIT program. However, both CPET and 6MWT are important perioperative risk stratification tests for patients who undergo complex lung cancer surgeries.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Jones LW, Peddle CJ, Eves ND, Haykowsky MJ, Courneya KS, Mackey JR, et al. Effects of presurgical exercise training on cardiorespiratory fitness among patients undergoing thoracic surgery for malignant lung lesions. Cancer 2007;110:590-8.  Back to cited text no. 1
    
2.
Levett DZH, Jack S, Swart M, Carlisle J, Wilson J, Snowden C, et al. Perioperative cardiopulmonary exercise testing (CPET): Consensus clinical guidelines on indications, organization, conduct, and physiological interpretation. Br J Anaesth 2018;120:484-500.  Back to cited text no. 2
    
3.
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4.
Keeratichananont W, Thanadetsuntorn C, Keeratichananont S. Value of preoperative 6-minute walk test for predicting postoperative pulmonary complications. Ther Adv Respir Dis 2016;10:18-25.  Back to cited text no. 4
    
5.
Castleberry A, Mulvihill MS, Yerokun BA, Gulack BC, Englum B, Snyder L, et al. The utility of 6-minute walk distance in predicting waitlist mortality for lung transplant candidates. J Heart Lung Transplant 2017;36:780-6.  Back to cited text no. 5
    
6.
Dong J, Mao Y, Li J, He J. Stair-climbing test predicts postoperative cardiopulmonary complications and hospital stay in patients with non-small cell lung cancer. Med Sci Monit 2017;23:1436-41.  Back to cited text no. 6
    
7.
Lee TH, Marcantonio ER, Mangione CM, Thomas EJ, Polanczyk CA, Cook EF, et al. Derivation and prospective validation of a simple index for prediction of cardiac risk of major noncardiac surgery. Circulation 1999;100:1043-9.  Back to cited text no. 7
    
8.
Davenport DL, Ferraris VA, Hosokawa P, Henderson WG, Khuri SF, Mentzer RM Jr. Multivariable predictors of postoperative cardiac adverse events after general and vascular surgery: Results from the patient safety in surgery study. J Am Coll Surg 2007;204:1199-210.  Back to cited text no. 8
    
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Botto F, Alonso-Coello P, Chan MT, Villar JC, Xavier D, Srinathan S, et al. Myocardial injury after noncardiac surgery: A large, international, prospective cohort study establishing diagnostic criteria, characteristics, predictors, and 30-day outcomes. Anesthesiology 2014;120:564-78.  Back to cited text no. 9
    
10.
Kaufmann KB, Loop T, Heinrich S, Working Group of the German Thorax Registry. Risk factors for post-operative pulmonary complications in lung cancer patients after video-assisted thoracoscopic lung resection: Results of the German Thorax Registry. Acta Anaesthesiol Scand 2019;63:1009-18.  Back to cited text no. 10
    
11.
Yang R, Wu Y, Yao L, Xu J, Zhang S, Du C, et al. Risk factors of postoperative pulmonary complications after minimally invasive anatomic resection for lung cancer. Ther Clin Risk Manag 2019;15:223-31.  Back to cited text no. 11
    
12.
Mugele H, Freitag N, Wilhelmi J, Yang Y, Cheng S, Bloch W, et al. High-intensity interval training in the therapy and aftercare of cancer patients: A systematic review with meta-analysis. J Cancer Surviv 2019;13:205-23.  Back to cited text no. 12
    
13.
Licker M, Karenovics W, Diaper J, Frésard I, Triponez F, Ellenberger C, et al. Short-term preoperative high-intensity interval training in patients awaiting lung cancer surgery: A randomized controlled trial. J Thorac Oncol 2017;12:323-33.  Back to cited text no. 13
    
14.
Bhatia C, Kayser B. Preoperative high-intensity interval training is effective and safe in deconditioned patients with lung cancer: A randomized clinical trial. J Rehabil Med 2019;51:712-8.  Back to cited text no. 14
    
15.
Stefanelli F, Meoli I, Cobuccio R, Curcio C, Amore D, Casazza D, et al. High-intensity training and cardiopulmonary exercise testing in patients with chronic obstructive pulmonary disease and non-small-cell lung cancer undergoing lobectomy. Eur J Cardiothorac Surg 2013;44:e260-5.  Back to cited text no. 15
    
16.
Sperandio EF, Arantes RL, Matheus AC, Silva RP, Lauria VT, Romiti M, et al. Intensity and physiological responses to the 6-minute walk test in middle-aged and older adults: A comparison with cardiopulmonary exercise testing. Braz J Med Biol Res 2015;48:349-53.  Back to cited text no. 16
    
17.
Miyamoto S, Nagaya N, Satoh T, Kyotani S, Sakamaki F, Fujita M, et al. Clinical correlates and prognostic significance of six-minute walk test in patients with primary pulmonary hypertension. Comparison with cardiopulmonary exercise testing. Am J Respir Crit Care Med 2000;161:487-92.  Back to cited text no. 17
    
18.
Lee H, Kim HK, Kang D, Kong S, Lee JK, Lee G, et al. Prognostic value of 6-min walk test to predict postoperative cardiopulmonary complications in patients with non-small cell lung cancer. Chest 2020;157:1665-73.  Back to cited text no. 18
    
19.
Brunelli A, Kim AW, Berger KI, Addrizzo-Harris DJ. Physiologic evaluation of the patient with lung cancer being considered for resectional surgery: Diagnosis and management of lung cancer, 3rd ed.: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2013;143:e166S-90.  Back to cited text no. 19
    


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