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Evidence: for risk or for management?
- Gortdon B Drummond (10 January 2009)
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Cardiopulmonary Exercise Testing for Objective Assessment of Operative Risk
- Adrian Hall, Paul Older (29 December 2008)
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Perioperative risk estimation with general population data
- John B Carlisle (11 December 2008)
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Gortdon B Drummond
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I enjoyed this exchange between the Bayesian epidemiologist and the Fisherian physiologists. They gave us a long well referenced exposition on size-based physiology (to my thinking, a tricky matter in medicine) but then end with an ex cathedra statement which is unsubstantiated in the letter: "In assessing surgical risk fallacies persist regarding the value of stair climbing tests, peak or maximum exercise tests, and use of METs for estimates of the metabolic costs of physical activity. Such estimates, tests or methods are very misleading and of little value. There is no substitute for the objective measurement of oxygen uptake and carbon dioxide elimination using a symptom limited, submaximal, incremental, ramp protocol CPET of each patient." Perhaps we could have some supporting evidence for this paragraph, slanted please in a way that the worried clinician, with more patients than ITU beds, can apply. In other words: when faced with an old man from a poor background, will any test help decide if he gets that last ITU bed for his postoperative care? If there are tests that show how the ITU care will get him out of hospital, perhaps faster than if he had been sent to the ward after his surgery, how can we tell which is a good test and which is a less good one? It seems to me that this clinical conundrum has not yet been adequately addressed in any of the tests. Conflict of Interest:None declared |
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Adrian Hall, Anaethetist & Intensivist Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia, Paul Older
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To the Editor: Our work on pre-operative assessment (1), quoted by Struthers et al (2) and in the editorial by Reilly (3), used anaerobic threshold (AT) determined by a cardiopulmonary exercise test (CPET) and showed that patients undergoing major surgery with decreased cardiopulmonary reserve have increased post- operative risk. Unfortunately both Struthers et al and Reilly maintain fallacies relating to assessment of cardiopulmonary reserve. Decreased cardiopulmonary reserve means decreased ability to transfer oxygen to metabolising tissue. It may be expressed in terms of a reduction in AT or in the oxygen consumption/work rate relationship. Determination of the AT is of most relevance to the post-operative state because it relates to sustainable aerobic metabolism. Importantly, although expressed in terms of oxygen uptake, the AT actually defines a point of increased carbon dioxide elimination, not from increased metabolism of oxygen, but rather from onset of anaerobic metabolism and increasing lactate. Further, the AT is non- volitional, reproducible, occurs at a submaximal work rate, and is the basis for analysis of other important physiologic parameters. In our opinion, other measures of exercise capacity have significant disadvantages and no role in pre-operative assessment. Peak oxygen uptake is volitional and therefore not reproducible; maximum oxygen uptake is very specifically defined and achieved only rarely. These terms are often confused and frequently used erroneously. Importantly, neither relates oxygen uptake to carbon dioxide elimination and therefore do not define the onset of anaerobic metabolism. The American College of Cardiology and the American Heart Association (ACC/AHA) Guidelines 2007 (4) use the metabolic equivalent (MET) as an estimate of work performed at various levels of exercise. One MET is defined as 3.5 ml O2 min-1 kg-1 and thus four METs equal an oxygen uptake of 14 ml min-1 kg-1. The ACC/AHA Guidelines do not make clear whether the four METs stated as an acceptable level of function means aerobic metabolism below the AT, or anaerobic metabolism and increasing lactate. Further, it is not widely known that the term MET was first defined using the resting oxygen consumption of a single person, a 70 kg male of 40 years (5). No academic journal today would accept a definition based on such data. As well explained in the above reference, when a scientific convention gains widespread acceptance, there is a risk that its underlying premise may no longer be questioned. Where other workers have queried the underlying premise, the value of the MET was found to be significantly less than 3.5 ml O2 min-1 kg-1. Byrne et al (5) found the average resting metabolic rate (RMR or 1 MET) was 2.56 ± 0.40 ml O2 min-1 kg-1. Body composition is a major cause of variation in the value of resting oxygen uptake and exerts a greater effect than age. The original concept relating work to the basal metabolic rate (BMR) is credited to D.B. Dill in 1936 (6) at the famous Harvard Fatigue Laboratory, one of the first exercise laboratories. The term MET was first used by Gagge in 1941 (7). Although the concept has merit, comparisons using factorial METs are only of value if the oxygen uptake of one MET for each individual is known accurately. An average value, applied to the entire population regardless of body composition or age, is not a valid substitute. Reilly suggests the ability to climb two flights of stairs equates to an AT of 11 ml O2 min-1 kg-1. The equation used to derive power required for climbing is: Power (Watt) = [mass (kg) x 9.8 x vertical height (m)] / time (s) For relating power to oxygen uptake the equation is: Oxygen Uptake (ml min-1)= resting oxygen uptake (ml min-1) + Watt x10. In the instance quoted the vertical height is 6 metres; if we assume a mass of 70 kg and a nominal climbing time of 30 seconds, this would require energy expenditure of 137.2 Watts. If we also assume a resting oxygen uptake of 250 ml min-1 and that the subject was capable of sustaining this exercise, i.e. continuing to climb up a stairway at the rate of 6 metres every 30 seconds, the steady state oxygen uptake would be > 1600 ml O2 min-1 (23 ml O2 min-1 kg-1). However, climbing two flights of stairs in 30 seconds is not a steady state activity; indeed, it is not even an aerobic activity. There are significant and important differences in energy production and the kinetics of gas exchange between early and later exercise as well as exercise below and above the AT. What is the energy source in early exercise? In early exercise cellular energy is not derived from oxidative metabolism. The cell is unable to store the ATP needed for muscular activity but initially generates it from the anaerobic hydrolysis of large quantities of stored phosphocreatine to creatine and from the anaerobic glycolysis of carbohydrate to pyruvate. Only later (after about 30 seconds) in exercise under aerobic conditions does pyruvate enter the tricarboxylic acid cycle with continued generation of ATP. Climbing two flights of stairs in 30 seconds is not a valid test of aerobic capacity or cardiopulmonary reserve. The other suggestion that walking 600 m on a level course is equivalent to an AT of 11 ml O2 min-1 kg-1 does not specify the mass, body mass index or body composition of the patient nor the walking speed. The ACC/AHA Guidelines suggest that the subject should perform the walk at approximately 6 km h-1, i.e. 600 m in 6 minutes. The average energy expenditure for such activity is variously estimated as 100 Watt or 4 METs (8) and has been measured at >15 ml O2 min-1 kg-1, around 4.5 to 5.5 times resting metabolic rate (5). However, as discussed previously, such estimates or averages are not applicable to an individual and without measurement of gas exchange it is impossible to know if a subject is below or above their AT. In assessing surgical risk fallacies persist regarding the value of stair climbing tests, peak or maximum exercise tests, and use of METs for estimates of the metabolic costs of physical activity. Such estimates, tests or methods are very misleading and of little value. There is no substitute for the objective measurement of oxygen uptake and carbon dioxide elimination using a symptom limited, submaximal, incremental, ramp protocol CPET of each patient. The reason for all pre-operative testing is to define operative risk and thus the level of post-operative care required. Cardiopulmonary exercise testing reliably detects all patients at increased risk and, perhaps more significantly, those who have low operative risk with major surgery. In our series (1) this low risk group was approximately 50% of all patients tested; these patients needed no special care in the post-operative period. Accurate risk assessment is both a medical and an economic imperative and we must advocate for cardiopulmonary exercise testing to become more readily available to all anaesthetists. Dr Adrian Hall MB BS, FANZCA, FJFICM Consultant Anaesthetist and Intensivist Peter MacCallum Cancer Centre St. Andrews Place East Melbourne, Victoria 8006 Australia Phone + 61 3 9656 1538 Facsimile + 61 3 9656 1191 adrian_hall@bigpond.com Dr Paul Older MB BS, LRCP MRCS, FRCA, FANZCA, FFICANZCA, FJFICM Senior Lecturer Department of Medicine Melbourne University Parkville, Victoria 3010 Australia References 1. 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: 355-62 2. 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: 774-80 3. Reilly CS. Can we accurately assess an individual's perioperative risk? Br J Anaesth 2008; 101: 747-9 4. Fleisher LA, Beckman JA, Brown KA, 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: e418 - 99 5. Byrne NM, Hills AP, Hunter GR, Weinsier RL, Schutz Y. Metabolic equivalent: one size does not fit all. J Appl Physiol 2005; 99: 1112-9 6. Dill D. The economy of muscular exercise. Physiology Review 1936; 16: 263-91 7. Gagge AP, Burton AC, Bazett HC. A Practical System of Units for the Description of the Heat Exchange of Man with His Environment. Science 1941; 94: 428-30 8. Hlatky MA, Boineau RE, Higginbotham MB, et al. A brief self- administered questionnaire to determine functional capacity (the Duke Activity Status Index). Am J Cardiol 1989; 64: 651-4 Conflict of Interest:None declared |
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John B Carlisle, Consultant anaesthetist Torbay Hospital, Devon
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Editor I congratulate Dr Struthers and colleagues on their cardiopulmonary exercise (CPX) study.1 I wish to suggest a solution to problems identified by Professor Reilly that may be of use to anaesthetists, surgeons and patients, with or without a fitness test.2 For eight years we have incorporated CPX testing into our perioperative risk assessment and management service. We have begun to estimate preoperative mortality risk and median life expectancy for any scheduled patient from eight variables contained in their notes, to which we may add CPX-measured fitness to increase precision. We then generate a postoperative mortality risk by estimating the effect of a particular surgery on this preoperative risk. The absolute difference between these two risks helps to guide perioperative management. The survival of millions of people with and without symptomatic disease has been consistently linked to only about nine independent variables (but many confounding variables). This research dwarfs the ‘considerable [perioperative] research effort’.3 4 The risk of dying increases 5000 times between the ages of 9 and 90, doubling every 7 years.5 Between 10 and 70 years men are about 1.7 times more likely to die than women. At any age the risk that the fittest (97th centile) will die is a quarter to a third the risk of the least fit (3rd centile), decreasing by about 0.85 times with every MET.6 7 The destitute are twice as likely to die as the wealthy (educational qualification, job or income). These four variables form the basis of survival estimation. Five further independent variables (diagnosed morbidities) chronically increase risk about 1.5 times – history of: myocardial infarction; heart failure; stroke; peripheral arterial disease; renal failure (variously defined as [creatinine] more than 150 to 177 µmol L-1). For instance, the (average) rate at which 76 year-old men died between 2004 and 2006 in the United Kingdom was 1 in 255 per month (10 year life expectancy); an old myocardial infarction would increase this risk to 1 in 170 (1.5 in 255). This risk would increase to about 1 in 120 (6 year life expectancy) if the peak oxygen consumption during CPX testing was 15 ml O2 kg-1 min-1 (two METs less than predicted). One could use CPX variables other than peak O2 or anaerobic threshold to summarize fitness: in many studies ventilatory equivalents for carbon dioxide (Ve/VCO2) and oxygen (Ve/VO2) correlate better with subsequent survival.8-12 We and our patients are interested in both preoperative and postoperative mortality risk and quality of life. We are now comparing postoperative survival with calculated preoperative survival to examine how scheduled surgery (temporarily) increases mortality. For instance the mortality rate we have observed in the month following open abdominal aortic aneurysm repair is 12 to 14 times the preoperative risk.13 At the moment I think that: no single variable could ever adequately describe risk; mortality risk varies most with age upon which the average effects of the other independent variables act, bracketed by uncertainty (for instance 95% confidence intervals). I think that numerical thresholds – postoperative risk minus preoperative risk – should determine the intensity of perioperative care rather than the type of surgery, patient morbidity or aerobic fitness. The interaction of nine or more independent variables, characterized by average effect and associated uncertainties, suggests that it is a mistake to dichotomize populations into ‘high’ and ‘low’ risk groups. This interaction also implies that the precision of a ‘specific risk value’ hoped for by Professor Reilly could be estimated now from these data, which could then be used to predict whether further tests or research are likely to add clinically useful information. 1 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: 774-80. 2 Reilly CS. Can we accurately assess an individual’s perioperative risk? Br J Anaesth 2008; 101: 747-9. 3 Hippisley-Cox J, Coupland C, Vinigradova Y, Robson J, May M, Brindle P. Derivation and validation of QRISK, a new cardiovascular disease risk score for the United Kingdom: prospective open cohort study. Br Med J 2007; 335: 136-48. 4 Conroy RM, Pyörälä K, Fitzgerald AP et al. Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project. Eur Heart J 2003; 24: 987-1003. 5 http://www.gad.gov.uk/Demography_Data/Life_Tables/Interim_life_tables.asp 6 Myers J, Prakash M, Froelicher V, Do D, Partington S, Atwood JE. Exercise capacity and mortality among men referred for exercise testing. N Engl J Med 2002; 346: 793-801. 7 Gulati M, Black HR, Shaw LJ et al. The prognostic value of a nomogram for exercise capacity in women. N Engl J Med 2005; 353: 468-75. 8 Tsurugaya H, Adachi H, Kurabayashi M, Ohshima S, Taniguchi K. Prognostic impact of ventilatory efficiency in heart disease patients with preserved exercise tolerance. Circ J 2006; 70: 1332-6. 9 Koike A, Itoh H, Kato M et al. Prognostic power of ventilatory responses during submaximal exercise in patients with chronic heart disease. Chest 2002; 121: 1581-8. 10 Robbins M, Francis G, Pashkow FJ et al. Ventilatory and heart rate responses to exercise: better predictors of heart failure mortality than peak oxygen consumption. Circulation 1999; 100: 2411-7. 11 Corrà U, Mezzani A, Bosimini E, Giannuzzi P. Cardiopulmonary exercise testing and prognosis in chronic heart failure: a prognosticating algorithm for the individual patient. Chest 2004; 126: 942-50. 12 Gitt AK, Wasserman K, Kilkowski C et al. Exercise anaerobic threshold and ventilatory efficiency identify heart failure patients for high risk of early death. Circulation 2002; 106: 3079-84. 13 Carlisle J, Swart M. Mid-term survival after elective abdominal aortic aneurysm surgery predicted by cardiopulmonary exercise testing. Br J Surg 2007; 94: 966-9. Conflict of Interest:None declared |
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