The Role of Cardiopulmonary Exercise Testing as a Risk Assessment Tool in Patients Undergoing Oesophagectomy: A Systematic Review and Meta-analysis

Abstract

Introduction

Cardiopulmonary exercise testing (CPET) is an objective method of assessing functional capacity to meet the metabolic demands of surgery and has been adopted as a preoperative risk-stratification tool for patients undergoing major procedures. The two main measures are the peak rate of oxygen uptake during exercise (\(\dot{{\text{V}}}\)O2peak) and anaerobic threshold (AT), the point at which anaerobic metabolism exceeds aerobic metabolism during exercise. This systematic review and meta-analysis evaluates the predictive value of CPET for patients undergoing oesophagectomy.

Methods

A systematic literature search was conducted in databases of CINAHL, Cochrane Library, EMBASE, MEDLINE, PubMed, and Scopus to identify studies that examined associations between preoperative CPET variables and postoperative outcomes following oesophagectomy. Results were presented as standardised mean difference (SMD) with 95% confidence interval.

Results

Seven studies were included in this review. Preoperative \(\dot{{\text{V}}}\)O2peak moderately correlated with cardiopulmonary complications [SMD = − 0.43; 95% confidence interval (CI) − 0.77 to − 0.09; p = 0.013; I2 = 80.4%], unplanned ICU admissions (SMD = − 0.34; 95% CI − 0.60 to − 0.08; p = 0.011; I2 = 0.0%), and 1-year survival (SMD = 0.31; 95% CI 0.02–0.61; p = 0.045; I2 = 0.0%). Preoperative AT values moderately correlated with unplanned ICU admissions (SMD = − 0.34; 95% CI − 0.61 to − 0.07; p = 0.014; I2 = 0.0%), and 1-year survival (SMD = 0.34; 95% CI 0.00–0.68; p = 0.049; I2 = 7.4%). Neither \(\dot{{\text{V}}}\)O2peak nor AT demonstrated prognostic value for noncardiopulmonary complications.

Conclusions

\(\dot{{\text{V}}}\)O2peak and AT, where measured by preoperative CPET testing, are inversely associated with postoperative cardiopulmonary complications, unplanned ICU admissions, and 1-year survival following oesophagectomy. This meta-analysis was not able to identify an absolute cutoff value for CPET variables to discriminate between patients of varying levels of operative risk.

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References

  1. 1.

    Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.

    PubMed  Article  Google Scholar 

  2. 2.

    Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355(1):11–20.

    CAS  PubMed  Article  Google Scholar 

  3. 3.

    van Hagen P, Hulshof MC, van Lanschot JJ, Steyerberg EW, van Berge Henegouwen MI, Wijnhoven BP, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012;366(22):2074–84.

    PubMed  Article  Google Scholar 

  4. 4.

    Finks JF, Osborne NH, Birkmeyer JD. Trends in hospital volume and operative mortality for high-risk surgery. Ne Engl J Med. 2011;364(22):2128–37.

    CAS  Article  Google Scholar 

  5. 5.

    Markar S, Gronnier C, Duhamel A, Bigourdan JM, Badic B, du Rieu MC, et al. Pattern of postoperative mortality after esophageal cancer resection according to center volume: results from a large european multicenter study. Ann Surg Oncol. 2015;22(8):2615–23.

    PubMed  Article  Google Scholar 

  6. 6.

    Lapar DJ, Stukenborg GJ, Lau CL, Jones DR, Kozower BD. Differences in reported esophageal cancer resection outcomes between national clinical and administrative databases. J Thorac Cardiovasc Surg. 2012;144(5):1152–7.

    PubMed  Article  Google Scholar 

  7. 7.

    Low DE, Kuppusamy MK, Alderson D, Cecconello I, Chang AC, Darling G, et al. Benchmarking complications associated with esophagectomy. Ann Surg 2019;269(2):291–8.

    Article  PubMed  Google Scholar 

  8. 8.

    Feeney C, Hussey J, Carey M, Reynolds JV. Assessment of physical fitness for esophageal surgery, and targeting interventions to optimize outcomes. Dis Esophagus. 2010;23(7):529–39.

    CAS  PubMed  Article  Google Scholar 

  9. 9.

    Older P, Hall A. Cardiopulmonary exercise testing in preoperative risk assessment and patient management. Br J Anaesth. 2017;119(4):837–8.

    CAS  PubMed  Article  Google Scholar 

  10. 10.

    Snowden CP, Prentis J, Jacques B, Anderson H, Manas D, Jones D, et al. Cardiorespiratory fitness predicts mortality and hospital length of stay after major elective surgery in older people. Ann Surg. 2013;257(6):999–1004.

    PubMed  Article  Google Scholar 

  11. 11.

    Hennis PJ, Meale PM, Grocott MP. Cardiopulmonary exercise testing for the evaluation of perioperative risk in non-cardiopulmonary surgery. Postgrad Med J. 2011;87(1030):550–7.

    PubMed  Article  Google Scholar 

  12. 12.

    Tekkis PP, McCulloch P, Poloniecki JD, Prytherch DR, Kessaris N, Steger AC. Risk-adjusted prediction of operative mortality in oesophagogastric surgery with O-POSSUM. Br J Surg. 2004;91(3):288–95.

    CAS  PubMed  Article  Google Scholar 

  13. 13.

    Charlson M, Szatrowski TP, Peterson J, Gold J. Validation of a combined comorbidity index. J Clin Epidemiol. 1994;47(11):1245–51.

    CAS  PubMed  Article  Google Scholar 

  14. 14.

    Murray P, Whiting P, Hutchinson SP, Ackroyd R, Stoddard CJ, Billings C. Preoperative shuttle walking testing and outcome after oesophagogastrectomy. Br J Anaesth. 2007;99(6):809–11.

    CAS  PubMed  Article  Google Scholar 

  15. 15.

    Hightower CE, Riedel BJ, Feig BW, Morris GS, Ensor JE, Jr., Woodruff VD, et al. A pilot study evaluating predictors of postoperative outcomes after major abdominal surgery: Physiological capacity compared with the ASA physical status classification system. Br J Anaesth. 2010;104(4):465–71.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  16. 16.

    Reeh M, Metze J, Uzunoglu FG, Nentwich M, Ghadban T, Wellner U, et al. The PER (Preoperative Esophagectomy Risk) score: a simple risk score to predict short-term and long-term outcome in patients with surgically treated esophageal cancer. Medicine (Baltimore). 2016;95(7):e2724.

    PubMed  PubMed Central  Article  Google Scholar 

  17. 17.

    Struthers R, Erasmus P, Holmes K, Warman P, Collingwood A, Sneyd JR. Assessing fitness for surgery: a comparison of questionnaire, incremental shuttle walk, and cardiopulmonary exercise testing in general surgical patients. Br J Anaesth. 2008;101(6):774–80.

    CAS  PubMed  Article  Google Scholar 

  18. 18.

    Ridgway ZA, Howell SJ. Cardiopulmonary exercise testing: a review of methods and applications in surgical patients. Eur J Anaesthesiol. 2010;27(10):858–65.

    PubMed  Article  Google Scholar 

  19. 19.

    Smith TB, Stonell C, Purkayastha S, Paraskevas P. Cardiopulmonary exercise testing as a risk assessment method in non cardio-pulmonary surgery: a systematic review. Anaesthesia. 2009;64(8):883–93.

    CAS  PubMed  Article  Google Scholar 

  20. 20.

    Lam S, Hart A. Cardiopulmonary exercise testing for predicting early outcomes after major cancer resection: a systematic review. J Anesth Periop Med. 2018;5:136–48.

    CAS  Article  Google Scholar 

  21. 21.

    Hayden JA, van der Windt DA, Cartwright JL, Cote P, Bombardier C. Assessing bias in studies of prognostic factors. Ann Intern Med. 2013;158(4):280–6.

    PubMed  Article  Google Scholar 

  22. 22.

    Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097.

    PubMed  PubMed Central  Article  Google Scholar 

  23. 23.

    Nagamatsu Y, Shima I, Yamana H, Fujita H, Shirouzu K, Ishitake T. Preoperative evaluation of cardiopulmonary reserve with the use of expired gas analysis during exercise testing in patients with squamous cell carcinoma of the thoracic esophagus. J Thorac Cardiovasc Surg. 2001;121(6):1064–8.

    CAS  PubMed  Article  Google Scholar 

  24. 24.

    Forshaw MJ, Strauss DC, Davies AR, Wilson D, Lams B, Pearce A, et al. Is cardiopulmonary exercise testing a useful test before esophagectomy? Ann Thorac Surg. 2008;85(1):294–9.

    PubMed  Article  Google Scholar 

  25. 25.

    Lam S, Alexandre L, Hardwick G, Hart AR. The association between preoperative cardiopulmonary exercise-test variables and short-term morbidity after esophagectomy: a hospital-based cohort study. Surgery. 2019;166(1):28–33.

    PubMed  Article  Google Scholar 

  26. 26.

    Moyes LH, McCaffer CJ, Carter RC, Fullarton GM, Mackay CK, Forshaw MJ. Cardiopulmonary exercise testing as a predictor of complications in oesophagogastric cancer surgery. Ann Royal Coll Surg Engl. 2013;95(2):125–30.

    CAS  Article  Google Scholar 

  27. 27.

    Patel N, Powell AG, Wheat JR, Brown C, Appadurai IR, Davies RG, et al. Cardiopulmonary fitness predicts postoperative major morbidity after esophagectomy for patients with cancer. Physiol Rep. 2019;7(14):e14174.

    PubMed  PubMed Central  Article  Google Scholar 

  28. 28.

    Sinclair RCF, Phillips AW, Navidi M, Griffin SM, Snowden CP. Pre-operative variables including fitness associated with complications after oesophagectomy. Anaesthesia. 2017;72(12):1501–7.

    CAS  PubMed  Article  Google Scholar 

  29. 29.

    Whibley J, Peters CJ, Halliday LJ, Chaudry AM, Allum WH. Poor performance in incremental shuttle walk and cardiopulmonary exercise testing predicts poor overall survival for patients undergoing esophago-gastric resection. Eur J Surg Oncol. 2018;44(5):594–9.

    PubMed  Article  Google Scholar 

  30. 30.

    Beaver WL, Wasserman K, Whipp BJ. A new method for detecting anaerobic threshold by gas exchange. J Appl Physiol (Bethesda, Md: 1985). 1986;60(6):2020–7.

  31. 31.

    Patel N, Wheat J, Brown C, Powell A, Abdelrahman T, Davies R, et al. Prognostic value of cardiopulmonary exercise testing for morbidity risk and survival after oesophagectomy for cancer. United Eur Gastroenterol J. 2017;5 (5 Supplement 1):A709.

  32. 32.

    Trotti A, Colevas AD, Setser A, Rusch V, Jaques D, Budach V, et al. CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Sem Radiat Oncol. 2003;13(3):176–81.

  33. 33.

    Clavien PA, Sanabria JR, Strasberg SM. Proposed classification of complications of surgery with examples of utility in cholecystectomy. Surgery. 1992;111(5):518–26.

    CAS  PubMed  Google Scholar 

  34. 34.

    Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205–13.

    PubMed  PubMed Central  Article  Google Scholar 

  35. 35.

    Strasberg SM, Linehan DC, Hawkins WG. The accordion severity grading system of surgical complications. Ann Surg. 2009;250(2):177–86.

    PubMed  Article  Google Scholar 

  36. 36.

    Kwak SG, Kim JH. Central limit theorem: the cornerstone of modern statistics. Korean J Anesthesiol. 2017;70(2):144–56.

    PubMed  PubMed Central  Article  Google Scholar 

  37. 37.

    Older PO, Levett DZH. Cardiopulmonary Exercise Testing and Surgery. Ann Am Thorac Soc. 2017;14(Supplement_1):S74–83.

  38. 38.

    Levett DZ, Grocott MP. Cardiopulmonary exercise testing, prehabilitation, and Enhanced Recovery After Surgery (ERAS). Canadian J Anaesth. 2015;62(2):131–42.

    Article  Google Scholar 

  39. 39.

    Older P, Smith R, Courtney P, Hone R. Preoperative evaluation of cardiac failure and ischemia in elderly patients by cardiopulmonary exercise testing. Chest. 1993;104(3):701–4.

    CAS  PubMed  Article  Google Scholar 

  40. 40.

    Kusano C, Baba M, Takao S, Sane S, Shimada M, Shirao K, et al. Oxygen delivery as a factor in the development of fatal postoperative complications after oesophagectomy. Br J Surg. 1997;84(2):252–7.

    CAS  PubMed  Article  Google Scholar 

  41. 41.

    Hall A, Older P. Cardiopulmonary Exercise Testing Accurately Predicts Risk of Major Surgery Including Esophageal Resection: Letter 1. Ann Thorac Surg. 2009;87(2):670–1.

    PubMed  Article  Google Scholar 

  42. 42.

    Ney M, Haykowsky MJ, Vandermeer B, Shah A, Ow M, Tandon P. Systematic review: pre- and post-operative prognostic value of cardiopulmonary exercise testing in liver transplant candidates. Aliment Pharmacol Ther. 2016;44(8):796–806.

    CAS  PubMed  Article  Google Scholar 

  43. 43.

    Kumar R, Garcea G. Cardiopulmonary exercise testing in hepato-biliary and pancreas cancer surgery: a systematic review. Are we any further than walking up a flight of stairs? Int J Surg (London, Engl). 2018;52:201–7.

  44. 44.

    Lee CHA, Kong JC, Ismail H, Riedel B, Heriot A. Systematic review and meta-analysis of objective assessment of physical fitness in patients undergoing colorectal cancer surgery. Dis Colon Rectum. 2018;61(3):400–9.

    PubMed  Google Scholar 

  45. 45.

    Robertson SA, Skipworth RJ, Clarke DL, Crofts TJ, Lee A, de Beaux AC, et al. Ventilatory and intensive care requirements following oesophageal resection. Ann Royal Coll Surg Engl. 2006;88(4):354–7.

    CAS  Article  Google Scholar 

  46. 46.

    Park DP, Welch CA, Harrison DA, Palser TR, Cromwell DA, Gao F, et al. Outcomes following oesophagectomy in patients with oesophageal cancer: a secondary analysis of the ICNARC Case Mix Programme Database. Crit Care (London, Engl). 2009;13 Suppl 2:S1.

    Article  Google Scholar 

  47. 47.

    Older P, Hall A, Hader R. Cardiopulmonary exercise testing as a screening test for perioperative management of major surgery in the elderly. Chest. 1999;116(2):355–62.

    CAS  PubMed  Article  Google Scholar 

  48. 48.

    Huddart S, Young EL, Smith RL, Holt PJ, Prabhu PK. Preoperative cardiopulmonary exercise testing in England—a national survey. Periop Med (London, Engl). 2013;2(1):4.

    Article  Google Scholar 

  49. 49.

    Congedo E, Aceto P, Petrucci R, Mascia A, Gualtieri E, De Cosmo G. Preoperative anesthetic evaluation and preparation in patients requiring esophageal surgery for cancer. Rays. 2005;30(4):341–5.

    PubMed  Google Scholar 

  50. 50.

    Moran J, Wilson F, Guinan E, McCormick P, Hussey J, Moriarty J. Role of cardiopulmonary exercise testing as a risk-assessment method in patients undergoing intra-abdominal surgery: a systematic review. Br J Anaesth. 2016;116(2):177–91.

    CAS  PubMed  Article  Google Scholar 

  51. 51.

    Garcia DO, Thomson CA. Physical activity and cancer survivorship. Nutr Clin Pract. 2014;29(6):768–79.

    PubMed  PubMed Central  Article  Google Scholar 

  52. 52.

    Wijeysundera DN, Pearse RM, Shulman MA, Abbott TEF, Torres E, Ambosta A, et al. Assessment of functional capacity before major non-cardiac surgery: an international, prospective cohort study. Lancet (London, Engl). 2018;391(10140):2631–40.

    Article  Google Scholar 

  53. 53.

    Doganay E, Moorthy K. Prehabilitation for esophagectomy. J Thorac Dis. 2019;11(Suppl 5):S632–8.

    PubMed  PubMed Central  Article  Google Scholar 

  54. 54.

    Arena R, Myers J, Williams MA, Gulati M, Kligfield P, Balady GJ, et al. Assessment of functional capacity in clinical and research settings: a scientific statement from the American Heart Association Committee on Exercise, Rehabilitation, and Prevention of the Council on Clinical Cardiology and the Council on Cardiovascular Nursing. Circulation. 2007;116(3):329–43.

    PubMed  Article  Google Scholar 

  55. 55.

    Palange P, Ward SA, Carlsen KH, Casaburi R, Gallagher CG, Gosselink R, et al. Recommendations on the use of exercise testing in clinical practice. Eur Respir J. 2007;29(1):185–209.

    CAS  PubMed  Article  Google Scholar 

  56. 56.

    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(3):484–500.

    CAS  PubMed  Article  Google Scholar 

  57. 57.

    Balady GJ, Arena R, Sietsema K, Myers J, Coke L, Fletcher GF, et al. Clinician’s Guide to cardiopulmonary exercise testing in adults: a scientific statement from the American Heart Association. Circulation. 2010;122(2):191–225.

    PubMed  Article  Google Scholar 

  58. 58.

    Herdy AH, Ritt LE, Stein R, Araujo CG, Milani M, Meneghelo RS, et al. Cardiopulmonary exercise test: background, applicability and interpretation. Arquivos Brasil Cardiol. 2016;107(5):467–81.

    CAS  Google Scholar 

  59. 59.

    Weber KT, Janicki JS. Cardiopulmonary exercise testing for evaluation of chronic cardiac failure. Am J Cardiol. 1985;55(2):22a–31a.

    CAS  PubMed  Article  Google Scholar 

  60. 60.

    Fleisher LA, Beckman JA, Brown KA, Calkins H, Chaikof E, Fleischmann KE, et al. ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery): developed in collaboration with the American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, and Society for Vascular Surgery. Circulation. 2007;116(17):e418–99.

    PubMed  Google Scholar 

  61. 61.

    Wilson RJ, Davies S, Yates D, Redman J, Stone M. Impaired functional capacity is associated with all-cause mortality after major elective intra-abdominal surgery. Br J Anaesth. 2010;105(3):297–303.

    CAS  PubMed  Article  Google Scholar 

  62. 62.

    Sjoquist KM, Burmeister BH, Smithers BM, Zalcberg JR, Simes RJ, Barbour A, et al. Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. Lancet Oncol. 2011;12(7):681–92.

    PubMed  Article  Google Scholar 

  63. 63.

    Allum WH, Stenning SP, Bancewicz J, Clark PI, Langley RE. Long-term results of a randomized trial of surgery with or without preoperative chemotherapy in esophageal cancer. J Clin Oncol. 2009;27(30):5062–7.

    PubMed  Article  Google Scholar 

  64. 64.

    Navidi M, Phillips AW, Griffin SM, Duffield KE, Greystoke A, Sumpter K, et al. Cardiopulmonary fitness before and after neoadjuvant chemotherapy in patients with oesophagogastric cancer. Br J Surg. 2018;105(7):900–6.

    CAS  PubMed  Article  Google Scholar 

  65. 65.

    Thomson IG, Wallen MP, Hall A, Ferris R, Gotley DC, Barbour AP, et al. Neoadjuvant therapy reduces cardiopulmunary function in patients undegoing oesophagectomy. Int J Surg (London, Engl). 2018;53:86–92.

    Article  Google Scholar 

  66. 66.

    von Dobeln GA, Nilsson M, Adell G, Johnsen G, Hatlevoll I, Tsai J, et al. Pulmonary function and cardiac stress test after multimodality treatment of esophageal cancer. Pract Radiat Oncol. 2016;6(3):e53–e9.

    Article  Google Scholar 

  67. 67.

    Goodyear SJ, Yow H, Saedon M, Shakespeare J, Hill CE, Watson D, et al. Risk stratification by pre-operative cardiopulmonary exercise testing improves outcomes following elective abdominal aortic aneurysm surgery: a cohort study. Periop Med (London, Engl). 2013;2(1):10.

    Article  Google Scholar 

  68. 68.

    Leclerc K. Cardiopulmonary exercise testing: a contemporary and versatile clinical tool. Cleveland Clin J Med. 2017;84(2):161–8.

    Article  Google Scholar 

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Acknowledgements

The authors acknowledge the substantial contribution of investigators who kindly provided additional data requested from their original manuscripts: Dr. Arfon Powell (Cardiff University School of Medicine, Cardiff) and Dr. Christopher Peters (Imperial College London, St Mary’s Hospital, London).

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Correspondence to Jonathan Sivakumar MBBS, PGDipSurgAnat, MS.

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Sivakumar, J., Sivakumar, H., Read, M. et al. The Role of Cardiopulmonary Exercise Testing as a Risk Assessment Tool in Patients Undergoing Oesophagectomy: A Systematic Review and Meta-analysis. Ann Surg Oncol (2020). https://doi.org/10.1245/s10434-020-08638-9

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