Simulated altitude for prehabilitation: alternatives await in less rarified air

Brown et al. [1] investigated simulated altitude (hypoxic training) as a form of prehabilitation. Participants stayed in a residential hypoxia facility for 1 week in normoxic conditions and 1 week in hypoxic conditions (F_IO₂ 15%). Although haemoglobin and erythropoietin concentration appeared to increase across the hypoxic week, this came at significant cost (e.g. physiological/clinical, environmental, financial) and may have been, at least partly, artefactual.

Since the 1960s, we have understood the deleterious effects of inactivity on human physiological function, most obviously from bed rest studies. Although not strictly bed rest in the study by Brown et al. [1], participants were not allowed to leave the facility or perform any exercise or sustained physical activity, including preparation of their own meals. In this short time, irrespective of exposure, anaerobic threshold decreased by 8–9% (normoxic: 11.9 to 11.0 ml.min^-1.kg^-1; hypoxic 12.4 to 11.3 ml.min^-1.kg^-1) and peak oxygen consumption (peak $\dot{V}{O}_2$) by 4–7% (normoxic: 17.1–15.9 ml.min^-1.kg^-1; hypoxic: 17.8–17.1 ml.min^-1.kg^-1). In fact, peak exercise heart rate was 16 beats.min^-1 higher in the follow-up cardiopulmonary exercise test after hypoxic exposure; therefore, baseline peak $\dot{V}{O}_2$ seems likely to have been underestimated, representing an even larger decrease across the intervention. This rapid decrease in cardiorespiratory fitness is likely attributable to reduced plasma volume, secondary to the additional confinement and ensuing reduction in physical activity. This reduction in plasma volume also seems likely to have contributed to the observed increase in haemoglobin. The analogy of a glass of sugary water can provide some perspective. If some water leaves (evaporates), you are left with a sweeter concentrate. Similarly, if plasma volume in total blood is reduced, haemoglobin concentration is increased. Although the between- rather than within-participant standard deviations make inferences difficult for both normoxic and hypoxic interventions, the reported increases in haemoglobin concentration appear artefactual. Previous work has shown haemoglobin mass increases at approximately 1% per week [2], and this is when exercise and hypoxia are combined in ‘live high, train low’ studies.

Peak $\dot{V}{O}_2$ and anaerobic threshold have been shown to be prognostic surgical indicators [3, 4], both of which were rapidly degraded, to near clinically important prognostic cut-offs. However, it is also important to note, peak $\dot{V}{O}_2$ and anaerobic threshold are only surrogate markers for a constellation of physiological processes refined with regular physical activity or exercise, and regress with inactivity. In this study, they might, similarly, represent the broader and rapid degradation of systematic processes (cardiovascular, metabolic, haematological, musculoskeletal function) that contribute. While hypoxic training may elicit similar haematological changes to regular exercise training, it cannot, and should not, replace the holistic and pleiotropic effects of physical activity. Exercise specifically targets many other modifiable surgical risk factors such as frailty through favourable adaptations in musculoskeletal health and function; diabetes through improved blood glucose regulation; enhanced lipid oxidation; and reduced incidence of anxiety and depression. Exercise also induces cellular hypoxia among other stressors, triggering a cascade of responses that build resilience to future hypoxia, whether systemic (i.e. exercise or surgery) or localised (e.g. aortic clamping, arthroplasty tourniquet) [3].

Physical activity and exercise are time efficient, accessible and equitable therapies to optimise pre-operative fitness and health. Surgery is a uniquely motivating life event for patients to become physically active. A collaborative team and patient-centred approach is essential to capitalise on this motivation and empower patients to improve not only pre-operative health but also provide the skills and behaviour changes to maintain this during the rehabilitation period and beyond. Future prehabilitation work must focus on ecologically valid, accessible and equitable interventions that are sustainable from a lifestyle and financial perspective as well as, most importantly, an environmental and resource perspective.