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Stair Climbing Test Predicts Cardiopulmonary Complications After Lung Resection^*

^* From the Department of Thoracic Surgery, University of Ancona, Ancona, Italy.

Correspondence to: Alessandro Brunelli, MD, Via S. Margherita 23, Ancona 60129, Italy; e-mail: alexit_2000{at}yahoo.com

	Abstract

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Study objective: To evaluate the capability of the stair climbing test to predict cardiopulmonary complications after lung resection for lung cancer.

Design: A prospective cohort of candidates for lung resection. Spirometric assessment and the stair climbing test were performed the day before operation. Univariate and multivariate analyses were performed to identify predictors of postoperative complications.

Setting: Tertiary referral center.

Patients: A consecutive series of 160 candidates for lung resection with lung carcinoma from January 2000 through March 2001.

Results: At univariate analysis, the patients with complications were significantly older (p = 0.02), had a significantly lower FEV₁ percentage (p = 0.007) and predicted postoperative FEV₁ percentage (p = 0.01), had a greater incidence of a concomitant cardiac disease (p = 0.02), climbed a lower altitude at the stair climbing test (p < 0.0001), and had a lower calculated maximum oxygen consumption (O₂max) [p = 0.03] and predicted postoperative O₂max (p = 0.006) compared to the patients without complications. At multivariate analysis, the altitude reached at the stair climbing test remained the only significant independent predictor of complications.

Conclusions: The stair climbing test is a safe and economical exercise test, and it was the best predictor of cardiopulmonary complications after lung resection.

Key Words: complication • exercise test • lung resection • maximum oxygen consumption • stair climbing test

Exercise testing is increasingly used in the preoperative evaluation of candidates for lung resection in order to uncover severe deficits in systemic oxygen transport.¹ These may be the physiopathologic basis of postoperative cardiopulmonary complications.

The stair climbing test has been traditionally used by thoracic surgeons to select patients before operation.^{2 3} However, few studies have systematically analyzed this exercise methodology as a preoperative test.^{4 5 6 7} The aim of the present study was to prospectively assess the role of symptom-limited stair climbing in predicting cardiopulmonary complications after lung resection for non-small cell lung carcinoma.

	Materials and Methods

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One hundred sixty-six candidates for lung resection for non-small cell lung carcinoma from January 2000 through March 2001 were prospectively enrolled in the present analysis after giving informed consent. Six patients were excluded from the study: three patients for severe musculoskeletal disease and three patients for peripheral vascular disease. The remaining 160 patients (128 men and 32 women) formed the database of the analysis. Twenty-eight pneumonectomies, 111 lobectomies, and 21 wedge/segmentectomies were performed through a muscle-sparing lateral thoracotomy by the same surgical team. Preoperative functional evaluation consisted of spirometry and a symptom-limited stair climbing test.

For the purpose of the present study, the following spirometric variables were considered: FEV₁; carbon monoxide diffusion lung capacity corrected for alveolar volume (DLCO/VA); predicted postoperative FEV₁ (ppoFEV₁) calculated by the formula, (preoperative FEV₁/No. of preoperative functioning segments) x No. of postoperative functioning segments; predicted postoperative DLCO/VA (ppoDLCO/VA) calculated by the formula, (preoperative DLCO/VA/No. of preoperative functioning segments) x No. of postoperative functioning segments; and FEV₁/FVC. The estimate of the number of functioning segments was done by using quantitative perfusion lung scan. All the spirometric data, with the exception of FEV₁/FVC, were expressed as percentage of predicted for age, sex, and height.

The symptom-limited stair climbing test was performed the day before the operation. Our hospital has 16 flights of stairs, each flight having 11 steps. Each step is 0.155 m in height. The patients were asked to climb, at a pace of their own choice, the maximum number of steps and to stop only for exhaustion, limiting dyspnea, leg fatigue, or chest pain. The patients were accompanied by a physician during their exercise and encouraged to continue the test. Moreover, a continuous verbal interaction between the patients and the physician was used in order to assess the patients’ dyspnea and the occurrence of other symptoms. During the exercise, pulse rate and capillary oxygen saturation were monitored by means of a portable pulse oximeter. For each patient, the number of steps climbed and the time taken to complete the test were recorded. The following ergometric variables were calculated and used for the analysis: work (height of the step in meters x steps per minute x body weight in kilograms x 0.1635),⁴ maximum oxygen consumption (O₂max) in milliliters per minute (5.8 x weight in kilograms + 151 + 10.1 x work),⁴ O₂max corrected for body surface area in milliliters per minute squared, and oxygen pulse (O₂max divided by heart rate [HR]). Furthermore, a predicted postoperative O₂max (ppoO₂max) was calculated according to the number of functioning segments removed at operation and estimated by quantitative lung perfusion scan.^{8 9 10}

Maximum predicted HR was estimated by the following formula: 220 - age.¹¹ The HR reserve in percentage was calculated by the following equation: (predicted maximum HR - actual maximum HR)/predicted maximum HR x 100.¹¹

For the purpose of the present study, a concomitant cardiac disease was defined as follows: previous cardiac surgery, previous myocardial infarction, history of coronary artery disease, current treatment for hypertension, arrhythmia, or cardiac failure. All the patients with a concomitant cardiac disease underwent an extensive cardiac evaluation before performing the stair climbing test. No patients with a concomitant cardiac disease were excluded from this analysis after the cardiac evaluation, but they were allowed to perform the stair climbing only when considered to be in a hemodynamically stable state.

Postoperative cardiopulmonary complications were considered as those occurring within 30 days from the operation or during a longer period if the patient was still in the hospital. According to other authors^{12 13 14 15} and for the sake of comparison, the following complications were considered: respiratory failure requiring mechanical ventilation for > 48 h; pneumonia; atelectasis requiring bronchoscopy; pulmonary edema; pulmonary embolism; myocardial infarction; hemodynamically unstable arrhythmia requiring medical treatment; cardiac failure; and death.

Statistical Analysis
The comparison between patients with and without complications was made by means of the unpaired Student’s t test for continuous variables and by means of the ² test for categorical variables. The significant variables at the univariate analysis were entered in a multivariate logistic regression analysis in which the dependent variable was the presence of postoperative complications.

All the tests were two tailed, and p < 0.05 was considered statistically significant. The analysis was performed by using the Statview 5.0 software (SAS Institute; Cary, NC).

	Results

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Twenty-two patients in our series (13.8%) had 25 cardiopulmonary complications: pneumonia (n = 7), arrhythmia (n = 7), cardiac failure (n = 3), respiratory insufficiency (n = 3), pulmonary edema (n = 1), atelectasis (n = 1), and death (n = 3). The mean stair climbing test duration was 114.1 s (± 28.1 s). No patient experienced significant cardiac arrhythmia or other complications of the test. All 160 patients enrolled in the present study who performed the stair climbing test underwent surgery the following day. However, during the same period of the study, we evaluated two patients who were excluded from surgery. Both were candidates for pneumonectomy. One of them had a ppoFEV₁ of 28% of predicted and a ppoDLCO/VA of 30% of predicted, climbed only 10.2 m, with a O₂max of 18 mL/min/kg and a ppoO₂max of 10 mL/min/kg, and experienced a profound desaturation at peak exercise (from 98 to 83%). The other patient had a ppoFEV₁ of 40% of predicted and ppoDLCO/VA of 29% of predicted, climbed 10.2 m, with a O₂max of 21.4 mL/min/kg and a ppoO₂max of 10.4 mL/min/kg.

Table 1 shows the characteristics of the patients enrolled in the study. The results of the comparison between patients with complications and those without complications are shown in Tables 2 , 3 .

The only significant independent variable at the logistic regression analysis was the altitude (p = 0.003). Only 8 of 122 patients (6.5%) who climbed an altitude 14 m had complications develop, whereas 7 of 14 patients (50%) who were not able to climb at least 12 m had postoperative complications. Seven of 24 patients (29.2%) who climbed between 12 m and 14 m had complications develop.

	Discussion

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Exercise tests are regarded as global tests, capable of uncovering severe pathophysiologic abnormalities in the oxygen transport system. Those patients who cannot generate high oxygen consumption (O₂) on preoperative exercise testing may be similarly unable to do so in response to the hypermetabolic demands imposed by major surgery or its complications.¹⁶

Stair climbing is an economical and widely applicable test, and it has an honored tradition among thoracic surgeons.² The appeal of this symptom-limited test resides in its simplicity and brevity, the familiarity of the patient with the exercise, and the need of few personnel, expertise, and equipment. Moreover, it has been reported that stair climbing test yielded greater values of O₂ than cycle ergometry.^{5 17 18} This finding may be explained by the fact stair climbing is a more stressful exercise than cycle exercise, and it is extremely motivating for the patients who are pushed to reach a visible objective represented by the next landing. In fact, only 5% of our patients stopped the exercise without reaching the landing. With a rare exception,⁶ the results reported in the literature on stair climbing indicate a fairly good capability of this exercise test in predicting cardiopulmonary complications after lung resection.^{3 4 5 7}

In the present study, the univariate analysis showed that patients with complications were significantly older than patients without complications, confirming previous studies.^{19 20 21 22 23} FEV₁ percentage and ppoFEV₁ percentage were both significantly reduced in the population with cardiopulmonary complications, as reported also by others.^{7 21 24 25 26 27} The presence of a concomitant cardiac disease in our series was a significant predictor of complications at the univariate analysis, as in previous works.^{19 24 28}

The number of steps climbed was expressed as altitude in meters as proposed by Pate et al,⁷ in order to provide a standardized parameter. This variable was significantly reduced in the patients with complications compared to those without complications. Furthermore, the calculated O₂max and the ppoO₂max were also significantly lower in the group of patients with complications. This latter result confirmed other works that used cycle ergometry.^{12 13 14 15 29 30 31} In particular, we confirmed with a different exercise methodology the finding of Bolliger et al,¹⁰ that predicted postoperative O₂, calculated by using quantitative lung perfusion scan, was a significant predictor of postoperative cardiopulmonary events.

The altitude climbed by the patient remained the only significant predictor of complications when the effect of the other variables was controlled in a multiple regression analysis. In particular, only 6.5% of patients who climbed > 14 m in altitude had complications. However, 29.2% of patients who climbed between 12 m and 14 m and 50% of those who climbed < 12 m had postoperative complications. The progressive increase of cardiopulmonary morbidity rate with the reduction of the altitude climbed preoperatively indirectly demonstrated that stair climbing was a stressful test capable to reveal severe deficits in maximum aerobic capacity. Olsen et al⁴ found that the completion of at least three flights of stairs, corresponding in their hospital to 13 m of altitude, seemed to best separate the group of patients with complications from those without complications.

Although the mortality number in our series was small, it was noteworthy that all the three patients who died were not able to climb at least 12 m. In a high-risk group of patients, Holden et al⁵ found that four of five patients who died within 90 days of operation were not able to climb > 44 steps, corresponding in their case to 7.5 m of altitude.

The stair climbing test proved to be superior with respect to spirometric variables in discriminating patients who had complications develop. In a high-risk group of 17 patients identified by a ppoFEV₁ < 35% of predicted or by a ppoDLCO/VA < 35% of predicted, who would have been traditionally considered inoperable, we had only four complications and no mortality. These patients were judged operable based only on their performance on the stair climbing test. All of them had a O₂max > 15 mL/min/kg, confirming the cutoff value proposed by Morice et al³⁰ in a similar series. Moreover, 15 of our 17 high-risk patients reached an altitude > 14 m. This finding has important clinical implications. Patients otherwise considered inoperable by standard spirometric criteria should not be excluded from surgery if their performance at the stair climbing test indicates an adequate cardiopulmonary reserve.

We think stair climbing may be the first test to be done in the preoperative functional evaluation of candidates for lung resection. Those patients able to climb > 14 m are, in our opinion, sufficiently fit to undergo surgery without any further functional tests, including spirometry. Those who climb < 14 m, particularly those who do not reach 12 m, must be carefully evaluated in order to disclose and possibly correct any alteration of the oxygen transport system.

On the basis of the results of the present analysis, our current practice is to exclude from surgery (or possibly consider only for minor resection) patients who climb < 12 m, and have a ppoFEV₁ or a ppoDLCO/VA < 35% of predicted, respectively. However, we confidently operate on those patients who are able to climb > 12 m, even though they have a ppoFEV₁ or a ppoDLCO/VA < 35% of predicted.

In conclusion, the present prospective study showed that symptom-limited stair climbing was a simple, safe, and economical exercise test capable to predict postoperative cardiopulmonary complications. The usefulness of this test resides in its reliability in detecting those patients with a reduced aerobic capacity and with a subsequent increased risk of cardiopulmonary morbidity. In this particular group of patients, more sophisticated technologies should be then employed in order to identify and possibly correct any cause of impaired oxygen transport. Thus, we think the results of this study may warrant, after future independent confirmations, the routine use of this exercise test in the preoperative evaluation of candidates for lung resection, either for cancer or other reasons, as well as for other types of surgery.

	Footnotes

 
Abbreviations: DLCO/VA = carbon monoxide diffusion lung capacity corrected for alveolar volume; HR = heart rate; ppoDLCO/VA = predicted postoperative carbon monoxide diffusion lung capacity corrected for alveolar volume; ppoFEV₁ = predicted postoperative FEV₁; ppoO₂max = predicted postoperative maximum oxygen consumption; O₂ = oxygen consumption; O₂max = maximum oxygen consumption

Received for publication April 24, 2001. Accepted for publication October 2, 2001.

	References

TOP Abstract Materials and Methods Results Discussion References

 

1. Olsen, GN (1989) The evolving role of exercise testing prior to lung resection. Chest 95,218-225[Abstract/Free Full Text]
2. Souders, CR (1961) Clinical evaluation of the patient for thoracic surgery. Surg Clin N Am 41,545-556
3. Van Norstrand, D, Kjeslberg, MO, Humphrey, EW (1968) Preresectional evaluation of risk from pneumonectomy. Surg Gynecol Obstet 127,306-312[ISI][Medline]
4. Olsen, GN, Bolton, JWR, Weiman, DS, et al (1991) Stair climbing as an exercise test to predict the postoperative complications of lung resection: two years experience. Chest 99,587-590[Abstract/Free Full Text]
5. Holden, DA, Rice, TW, Stelmach, K, et al (1992) Exercise testing, 6-min walk, and stair climb in the evaluation of patients at high risk for pulmonary resection. Chest 102,1774-1779[Abstract/Free Full Text]
6. Colman, NC, Schraufnagel, DE, Rivington, RN, et al (1982) Exercise testing in evaluation of patients for lung resection. Am Rev Respir Dis 125,604-606[ISI][Medline]
7. Pate, P, Tenholder, MF, Griffin, JP, et al (1996) Preoperative assessment of the high-risk patient for lung resection. Ann Thorac Surg 61,1494-1500[Abstract/Free Full Text]
8. Corris, PA, Ellis, DA, Hawkins, T, et al (1987) Use of radionuclide scanning in the preoperative estimation of pulmonary function after pneumonectomy. Thorax 42,285-291[Abstract]
9. Puente-Maestu, L, De Lucas, P, Arnedillo, A, et al (1994) Prediction of maximal oxygen uptake after thoracic surgery by radionuclide perfusion scanning [abstract]. Am Rev Respir Dis 149,A785
10. Bolliger, CT, Wyser, C, Roser, H, et al (1995) Lung scanning and exercise testing for the prediction of postoperative performance in lung resection candidates at increased risk for complications. Chest 108,341-348[Abstract/Free Full Text]
11. Wasserman, K, Hansen, JE, Sue, DY, et al (1989) Principles of exercise testing and interpretation. Lea & Febiger Philadelphia, PA.
12. Smith, TP, Kinasewitz, GT, Tucker, WY, et al (1984) Exercise capacity as a predictor of post-thoracotomy morbidity. Am Rev Respir Dis 129,730-734[ISI][Medline]
13. Bechard, D, Wetstein, L (1987) Assessment of exercise oxygen consumption as preoperative criterion for lung resection. Ann Thorac Surg 44,344-349[Abstract]
14. Bolliger, CT, Jordan, P, Soler, M, et al (1995) Exercise capacity as a predictor of postoperative complications in lung resection candidates. Am J Respir Crit Care Med 151,1472-1480[Abstract]
15. Markos, J, Mullan, BP, Hillman, DR, et al (1989) Preoperative assessment as a predictor of mortality and morbidity after lung resection. Am Rev Respir Dis 139,902-910[ISI][Medline]
16. Gilbreth, EM, Weisman, IM (1994) Role of exercise stress testing in preoperative evaluation of patients for lung resection. Clin Chest Med 15,389-403[ISI][Medline]
17. Swinburn, CR, Wakefield, JM, Jones, PW (1985) Performance, ventilation, and oxygen consumption in three different types of exercise tests in patients with chronic obstructive lung disease. Thorax 40,581-586[Abstract]
18. Pollock, M, Roa, J, Benditt, J, et al (1993) Estimation of ventilatory reserve by stair climbing: a study in patients with chronic airflow obstruction. Chest 104,1378-1383[Abstract/Free Full Text]
19. Harpole, DH, Liptay, MJ, DeCamp, MM, et al (1996) Prospective analysis of pneumonectomy: risk factors for major morbidity and cardiac dysrhythmias. Ann Thorac Surg 61,977-982[Abstract/Free Full Text]
20. Gebitekin, C, Gupta, NK, Martin, PG, et al (1993) Long-term results in the elderly following pulmonary resection for non-small cell lung carcinoma. Eur J Cardiothorac Surg 7,653-656[Abstract]
21. Yano, T, Yokoyama, H, Fukuyama, Y, et al (1997) The current status of postoperative complications and risk factors after a pulmonary resection for primary lung cancer: a multivariate analysis. Eur J Cardiothorac Surg 11,445-449[Abstract]
22. Kearney, DJ, Lee, TH, Reilly, JJ, et al (1994) Assessment of operative risk in patients undergoing lung resection: importance of predicted pulmonary function. Chest 105,753-759[Abstract/Free Full Text]
23. Bolliger, CT, Perruchoud, AP (1998) Functional evaluation of the lung resection candidate. Eur Respir J 11,198-212[Abstract/Free Full Text]
24. Nagasaki, F, Fleinger, BJ, Martini, N (1982) Complications of surgery in the treatment of carcinoma of the lung. Chest 82,25-29[Abstract/Free Full Text]
25. Miller, JI (1993) Physiological evaluation of pulmonary function in the candidate for lung resection. Thorac Cardiovasc Surg 105,347-352
26. Wahi, R, McMurtrey, MJ, DeCaro, LF, et al (1989) Determinants of perioperative morbidity and mortality after pneumonectomy. Ann Thorac Surg 48,33-37[Abstract]
27. Ferguson, MK, Little, L, Rizzo, L, et al (1989) Diffusing capacity predicts morbidity and mortality after pulmonary resection. Thorac Cardiovasc Surg 96,894-900
28. Duque, JL, Ramos, G, Castrodeza, J, et al (1997) Early complications in surgical treatment of lung cancer: a prospective, multicenter study. Ann Thorac Surg 63,944-950[Abstract/Free Full Text]
29. Eugene, J, Brown, SE, Light, RW, et al (1982) Maximum oxygen consumption: a physiologic guide to pulmonary resection. Surg Forum 33,260-262
30. Morice, RC, Peters, EJ, Ryan, MB, et al (1992) Exercise testing in the evaluation of patients at high risk for complications from lung resection. Chest 101,356-361[Abstract/Free Full Text]
31. Brutsche, MH, Spiliopoulos, A, Bolliger, CT, et al (2000) Exercise capacity and extent of resection as predictors of surgical risk in lung cancer. Eur Respir J 15,828-832[Abstract]

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This Article Abstract Full Text (PDF) Free Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Article Archive Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (28) Citing Articles via Google Scholar Google Scholar Articles by Brunelli, A. Articles by Fianchini, A. Search for Related Content PubMed PubMed Citation Articles by Brunelli, A. Articles by Fianchini, A.