To our knowledge, this is the largest study to explore the relationship between oxygen uptake and haemoglobin concentration in the clinical setting, and the first to control for body mass with allometric (log-linear) scaling. Oxygen uptake at peak exercise and at the anaerobic threshold (AT) increased with haemoglobin concentration [Hb], after adjusting for measured confounding variables.
The [Hb] was 10 to 12 g dl-1 in 353 patients (20%) and <10 g dl-1 in 83 (5%) patients. Other studies have reported rates of anaemia between 5% and 76%, a range partly dependent upon the indication for surgery and definition of anaemia . The American College of Surgeons’ National Surgical Quality Improvement Program (ACS NSQIP) recently reported a similar prevalence of preoperative anaemia (30.4%) .
The mean AT of 11 ml kg-1 min-1 is similar to that reported by other studies of preoperative populations [7, 36, 37]. However, this value is 2 to 3 ml kg-1 min-1 less than gender-specific reference values for age and height . The mean peak in our population, 15.5 ml kg-1 min-1, is 11 ml kg-1 min-1 less than gender-specific reference values for age and height [38, 39]. The aim of allometric scaling is to appropriately account for body size (that is, the scaled variable no longer varies with body size) . Oxygen uptake is usually reported per unit body mass, ml kg-1 min-1, a scale that requires further adjustment for body size . In the obese, oxygen uptake expressed as ml kg-1 min-1 underestimates fitness and overestimates risk . In the cachectic patient this scale overestimates fitness and underestimates risk .
Both AT and peak increased with [Hb], for the whole population, across individual testing sites and across all groups, except hepatobiliary surgery. However, this relationship was weak and although being highly statistically significant does not necessarily reflect a magnitude of clinical association. Nonetheless, an increase in [Hb] by one standard deviation (that is, 1.8 g dl-1 rise in [Hb]) was associated with a 9.7% and 6.0% increase in weight-adjusted peak and AT. The [Hb] explained 9% and 6% of the variance in peak and AT respectively. The increase in AT and peak with [Hb] may be due to increased oxygen-carrying capacity, or patients who are not anaemic exercising more than patients who are anaemic, or due to confounding. For instance, sick patients may be both anaemic and less fit. In addition, differences in AT, to some extent (although probably small), may be explained by inherent variations in measurement and/or interpretation or physiological context .
The cause of anaemia may be important. The most common cause is reported to be chronic disease, the severity of which being related to the degree of systemic inflammation [45, 46]. Features of anaemia due to chronic disease include reduced red cell survival, impaired erythropoiesis, and impaired iron metabolism, all of which may reduce AT and peak, directly or in combination . Iron status was not routinely assessed in our cohort but may independently influence fitness markers in the absence of anaemia. For example, iron deficiency with or without anaemia is associated with reduced fitness [48–50].
This study had some limitations. The observational, cross-sectional and retrospective nature of the data generates causative hypotheses but does not test them . It would have been valuable to assess the association of overall survival and critical care use with both anaemia and oxygen uptake. The [Hb] may be an imprecise measure of blood oxygen carrying capacity, given that its value is influenced by disease- or therapy-related contractions or expansions in plasma volume. For instance, oxygen-carrying capacity may be normal if [Hb] is low due simply to an increase in intravascular volume. A better measure of oxygen-carrying capacity may thus be total mass of haemoglobin (tHb-mass). The tHb-mass displays a higher correlation with peak (r2 = 0.79) than either blood volume (r2 = 0.76) or [Hb] [52, 53]. The relatively small explained variance in AT and peak by [Hb] (oxygen carrying capacity) in the current study suggests that other factors may play an important role in determining aerobic capacity. For example, other physiological factors that may limit peak include pulmonary diffusing capacity, cardiac output and skeletal muscle limitations . Although it is suggested that the AT reflects an imbalance in oxygen demand-supply, that is, that AT reflects onset of anaerobiosis, this is a much-debated and controversial concept [44, 55]. In addition, variations in the AT, to some extent may be explained by inherent discrepancies in its measurement and/or interpretation .
Future studies of preoperative cardiopulmonary exercise testing should include [Hb] with long-term survival and quality of life as outcomes as well as considering alternative endpoints measured during exercise testing such as metabolic efficiency and the oxygen pulse .