Pressure ulcers (PUs) can occur in any situations where people are subjected to non-uniform distribution of pressure over a prolonged period. They can have devastating effects on the patients' well-being and in extreme conditions can prove fatal. In addition to traditional wisdom implicating mechanically induced ischaemia, there is strong evidence that other mechanisms play a role in the cascade of events which can initiate the PU damage process at the cellular level. Some of these refer to a metabolic imbalance with compromised delivery of nutrients and accumulation of waste products in the local environment of the cells. The approach of much research has focused on the measure of oxygen in compressed tissues as a means of predicting early damage. However, the present review adopting a hierarchical approach, using length scales ranging from cells through to human models, has revealed compelling evidence which highlights the importance of carbon dioxide levels and associated concentration of other metabolites, such as lactate and purines. The temporal profiles of these metabolites have been monitored in the various models subjected to periods of mechanical-induced loading where the localized cells have converted to anaerobic metabolism. They reveal threshold levels of carbon dioxide which might be indicative of early tissue damage during both mechanical-induced ischaemia and subsequent reperfusion and an appropriate sensor could be used in a similar manner to the long-standing "canary in a cage" method to detect toxic gasses in enclosed mines.