Respiratory Muscle Fatigue

Following publication of work indicating that the diaphragm behaves as other skeletal muscles,' Macklem and Roussos proposed that fatigue and failure of the respiratory muscles may occur in a number of clinical conditions, such as in premature babies, in atrophy of respiratory muscles after prolonged mechanical ventilation, in increased inspiratory loads (as in acute pulmonary edema), in neuromuscular weakness (as in quadriplegia) or in chronic obstructive pulmonary disease (COPD) patients. A decade later a considerable amount of experimental data on fatigue of the respiratory muscles has been gathered. Little progress, however, is evident in important clinical aspects, such as the estimation of its prevalence in patients, the absence of an effective bedside diagnostic test, and the lack of hard evidence for the existence of long-term fatigue in chronic disease. The lack of faster progress may be related to the limitations of the experimental approaches currently used. In fact, most studies on respiratory muscle fatigue, published over the last decade, were designed after the loading-until-failure approach used by Monod. It was hypothesized and found that acute loading can induce fatigue in clinical conditions, such as weaning from a mechanical ventilator,' exercise, adding inspiratory loads, or modifying the breathing pattern. However, in other clinical conditions, for example, those characterized by a slow progressive decrease in muscle force on a slow increase in respiratory loads (such as COPD, obesity, malnourished patients, kyphoscoliosis, lung fibrosis), fatigue development is less severe. Although these conditions can eventually progress to chronic respiratory failure, it is unlikely that muscle fatigue plays a significant role. What appears to be more important is the way in which the respiratory control system changes its pattern of muscle activation. For example, the drive to breathe, which is mainly regulated by feedback loops originating in neurochemical reflexes, can be varied. This might be compared to conditions of voluntary or constant drive in experimental fatigue. Furthermore, the loads imposed by disease can be sustained by varying the duration of inspiration-expiration time (Ti/TT) (allowing partial recovery of the muscles between breaths), by modifying tidal volume (VT) (changing muscle length or the amount of shortening), breathing frequency or flow rate (velocity of shortening), or by alternating the use of various inspiratory muscles (in contrast to imposed patterns used in experimental fatigue). There is also the possibility that feed forward reflexes from muscles with incipient fatigue may decrease the respiratory center's activation of those muscles and reduce ventilation to preserve muscle integrity. Hence, hypoventilation (and chronic ventilatory failure) of neuromuscular origin may be considered a survival strategy rather than failure of the respiratory muscles. Central modulation of muscle activity has been called central fatigue, however, there is no need to call fatigue a mechanism of unloading the respiratory muscles. It represents a mechanism of preservation of muscle integrity rather than an expression of functional insufficiency. The study of strategy of breathing patterns in chronically loaded patients seems a promising approach to learn about mechanisms available to the respiratory system and may help to design tests to understand ventilatory failure and the role of fatigue in it, if any. This article develops three aspects of respiratory muscle fatigue: definitions, mechanisms, and assessment.