In the respiratory muscles is the development of what is called muscle fatigue, which is characterized by a failure of motor output for a given neural input and, importantly, is relieved only by rest. In other words, once the muscle fails because of fatigue, a period of rest is required before force can once again be generated by the muscle [20,45,46]. However, it is not clear how often true muscle fatigue actually occurs, and the ventilatory muscles more often fail because the workload becomes too great for their potential output [47]. It is clear that supporting a septic patient with mechanical ventilation prevents death from ventilator failure, but the use of mechanical ventilation has further therapeutic value. Theincreased work by ventilatory muscles in patients with respiratory distress requires high oxygen consumption to maintain this activity, and accordingly more blood flow. The needs of the ventilatory muscles thus could potentially consume a large proportion of the available oxygen, especially under conditions of limited blood flow. One study [48] estimated that the respiratory muscles take up as much as 24 of oxygen consumed by the body in patients with respiratory distress, even though the total ventilation was in the range of 9 l/minute and thus normal. This value was obtained by comparing oxygen consumption before and after the onset of mechanical ventilation. The investigators argued that mechanical ventilation would therefore leave more oxygen to be consumed per minute by the rest of the body, which could be especially important in patients with limited cardiac function. However, the estimate of oxygen consumption by the ventilatory muscles was probably an overestimate because it would have included excess sympathetic EPZ-5676 chemical information activity associated with the respiratory distress. Subsequent animal studies further tested this issue. These studies showed that mechanically ventilating animals subjected to cardiogenic shock decreased respiratory muscle blood flow, and this was associated with an increase in flow to the brain and kidney [22,37]. The same was true in sepsis [36]. It was initially thought that the lower blood flow to vital organs with spontaneous breathing was due to a `steal phenomenon’, in that the vascular resistance in the working ventilator muscles falls and diverts the limited blood flow from vital organs to the ventilatory muscles [22]. In a study with markedly increased ventilator activity caused by oleic acid induced lung injury but normal cardiac function [29], total ventilator muscle flow accounted for 11 of total cardiac output, and oxygen consumption would be expected to follow a similar proportion of the total. In a model of cardiogenic shock but unobstructed lungs, ventilatory muscles accounted for 20 of cardiac output [22]. However, when cardiogenic shock was combined with increased elastic load, ventilatory muscle blood flow accounted for PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/26577270 only 8 of the total blood flow, probably because the more forceful muscle contraction began to limit flow and possibly because the muscles were beginning to fail [23]. Similarly, in a dog model of septic shock with a low cardiac output, ventilatory muscles accounted for 9 of blood flow [36]. Taken together, these studies indicate that unless there is a profound decrease in cardiac output, the energy and flow needs of the diaphragm do not have a major impact on other organs, although limitations in the ventilatory muscles themselves can have major consequences for th.