Respiratory muscle dysfunction
S. NAVA, F. RUBINI
Introduction
The respiratory system consists of two main parts, the lung and the ventilatory pump. The latter is formed by the bony structure of the thorax, the central respi- ratory controllers, the inspiratory and expiratory muscles and the nerve innervat- ing these muscles. Whereas failure of the lung leads to hypoxemia, failure of the ventilatory pump, in particular a dysfunction of the respiratory muscles, leads to hypercapnic respiratory failure. Respiratory muscle fatigue occurs when respira- tory muscle endurance is exceeded; that is, when the load against which the mus- cles must contract requires too great an effort for too long [ 1]. Healthy people never approach this threshold, below which diaphragm fatigue does not occur. In contrast, patients with severe chronic obstructive pulmonary disease (COPD) neuromuscular diseases may be dose to the threshold at rest and exceed it even with minor exertion [2, 3]. In September 1988 a workshop was held at Kansas State University to reassess the state of knowledge on respiratory muscle fatigue [4]. Muscle fatigue was defined as a condition in which there is a loss in the capacity for developing force and/or velocity of a muscle resulting from muscle activity and which is reversible by rest. Muscle weakness is a condition in which the capacity of a rested muscle to generate force is impaired.
According to Monod and Scherrer [5] the endurance time of a muscle (tHm) during a constant isometric contraction is inversely proportional to the force developed, according to the following equation:
t!im=---K' F/Fmax
where K is a constant and F is the portion of maximal force that the muscle can develop. During an intermittent effort, like the respiratory muscles during spon- taneous breathing, the time the contraction is maintained must be taken into account since this time is inversely proportional to tlimã The tension-time index of the human diaphragm (TTdi) was used by Bellemare and Grassino [1] as a measure of diaphragmatic exertion against inspiratory loads. TT di was defined as the product of the mean transdiaphragmatic pressure (Pdi) developed during contraction (expressed as a fraction of maximal P di) and the time of contraction relative to the total duration of the respiratory cycle {Ti/Ttot). The diaphragm develops fatigue in the course of repeated intermittents when TTdi exceeds val-
Respiratory muscle dysfunction 35 ues ranging from 0.15 to 0.18. Above this threshold the endurance time of the diaphragm is inversely related to TT diã In the course of their experiments pleural (Pp!) and abdominal (Pab) pressure changes were made to contribute equally to Pdi during inspiration. However, in most situations [6] in which breathing is held against inspiratory loads the Pp! swing is larger than the abdominal one, suggest- ing increased recruitment of inspiratory muscles attached to the rib cage in addition to the diaphragm. Zocchi et al [7] have recently shown that when adopt- ing this pattern of breathing the critical threshold of fatigue is higher than previ- ously described by TT di for diaphragm emphasis.
Three general types of fatigue have been described: central fatigue, transmis- sion fatigue and contractile fatigue [8].
Central fatigue is a reversible decrease in central neural respiratory drive caused by overuse of the muscles. There are two kinds of central fatigue: 1) motivational fatigue in which the level of respiratory effort drops off but can be restored by a voluntary super-effort. 2) non-motivational fatigue, where the mus- cle retains a normal response to electrical stimulation but no amount of exhorta- tion can increase the level of respiratory effort. Transmission fatigue is a reversible, exertion-induced impairment in the transmission of neural impulses through nerves or across neuromuscular junctions. Possible locations are the axonal branch points, the neuromuscular junction itself and the muscle mem- brane. Contractile fatigue is a reversible impairment in the contractile response of the muscles to neural impulses which is not caused by drugs. This kind of fatigue can be divided into two types: a transient type known as high-frequency (reduced response to stimulation frequencies of SO to 100Hz), and a long-lasting form known as low frequency fatigue (reduced response to stimulation frequen- cies of 10 to 20 Hz). The transient high-frequency fatigue might be caused by accumulations of toxic metabolic by products of contraction, by altered calcium or by decreased ATP concentrations. The long lasting low-frequency fatigue is probably caused by minor muscle injury that must be repaired before normal function is restored.
To the clinician the identification of the etiology of ventilatory failure is fun- damental to the appropriate therapeutic plan and in particular in assessing the supply of energy and the demands of the ventilatory muscles pump. Weakness and fatigue of the respiratory muscles are associated with several diseases and pathological conditions as follows.
a. Low Cardiac Ouput States. Aubier et al. [9] showed that cardiogenic shock in dogs resulted in failure of the ventilatory muscles, while Nava and Bellemare [ 10]
demonstrated that the main cause of respiratory muscle fatigue in this condition depends on central factors. Whatever the main cause, the death of the animals resulted from ventilatory failure. Field et al. [ 11] extended these findings to criti- cally ill patients requiring mechanical ventilation. They noted that these patients not only had an increased oxygen consumption by respiratory muscle, but also exhibited a diminished efficiency of the ventilatory pump. They postulated that mechanical ventilation in such a group would increase oxygen delivery to more vital organ systems.
36 S. Nava, F. Rubini
b. Nutrition. It is clear that many patients with COPD are malnourished. An important consequence of malnutrition and weight loss is a significant decrease in respiratory muscle mass, with related weakness [12]. In addition, acute deple- tion of certain trace elements dramatically interferes with muscle performance.
Hypophosphatemia [ 13] usually a consequence of increased excretion in patients with diminished stores, may result in ventilatory failure. Hypokaliemia and hypo- magnesemia [14] may also impair muscle performance to provoke incipient fatigue. In direct contrast to the malnourished thin patients, the physician is com- monly faced with obese patients, in whom ventilatory muscle strength has been reported to be reduced by 30 o/o [15]. Work of breathing is also increased due to elastic loading and the predilection for hypoventilation and ventilatory failure is therefore clear.
c. Collagen Vascular Disease. Polymyositis significantly reduces respiratory mus- cle strength below 50 o/o of predicted. Gibson et al. [16] noted that also in systemis lupus erythematosus the diaphragm failed to perform normally as measured by Pru and maximal inspiratory and expiratory pressures (MIP & MEP). As with to other collagen diseases, sclerodermia is well known to cause myositis and involves the diaphragm and intercostal muscles [ 17].
d. Neuromuscular Diseases. Respiratory muscle weakness is well documented in pathologies such as poliomelitis, kyfoscoliosis, Duchenne dystrophy, myastenia gravis and others. Chronic respiratory weakness is characterized by a reduction in pressure-generating capacity affecting the ability to inflate the lungs and to produce effective cough. Loss of strength is probably the major factor increasing the tidal/maximal pleural pressure ratio but also reductions in lung and chest wall compliance, distortion of the chest wall (i.e. scoliosis) and muscle stiffening often increase the tidal demands on the respiratory muscles. Of these diseases the most devastating presentations of acute ventilatory failure are represented by acute inflammatory polyneuritis [18] (Guillain-Barre' -Landry syndrome) and botulism [19] (through reduction of neuromuscular transmission by impaired acetylcholine release).
e. Endocrinopathy. Hypothyroidism may impair ventilatory pump function as reflected in a reduced vital capacity and maximal inspiratory pressure [20]. The skeletal myopathies seen for example in Cushing's syndrome and acromegaly could also affect the strength of respiratory muscles on a chronic basis [ 21].
f. Healthy Individuals. Healthy people never approach the diaphragm fatigue threshold, except for two conditions: a) during "extreme" physical exercise, such as marathon running [22] but not during shorter competitions [23] and b) during the expulsive period of labour [24].
g. Drugs. Several drugs (xanthines, beta2-agonists) have been shown to potentiate the inotropic properties of the respiratory muscles, however their effects are still controversial [25-28]. Fluorinated and non-fluorinated corticosteroids at high doses, among the most commonly used pharmaceutical preparations, may pro- duce significant impairment of the contractile and histochemical properties of the respiratory muscles leading to severe weakness [29, 30].
h. Chronic Obstructive Pulmonary Disease (COPD). This disease is characterized
Respiratory muscle dysfunction 37 by increased resistance to airflow, air trapping and hyperinflation of the lungs [31, 32]. The increased resistance to airflow increases the work of breathing and energy requirements. Hyperinflation puts the respiratory muscles at mechanical disadvantage, as lung volume increases the muscles are passively shortened by their own elasticity rather than by active contraction. Thus, COPD not only makes it harder to breathe but aslo impairs the capacity of the respiratory mus- cles to handle the added loads. The occurence of respiratory muscle fatigue have been shown to occur acutely in these patients [2]. Nonetheless, it is surprising that almost all studies have been performed in a laboratory setting, the subjects being asked to modify their natural breathing pattern or to breathe against high inspiratory resistance. Only indirect evidence of acute respiratory muscle fatigue has therefore been described in "natural" conditions such as disconnection from mechanical ventilation [ 33] and asthmatic attack [ 34]. Evidence of "chronic" res- piratory muscle fatigue has never been demonstrated and its existance is still controversial. Indeed Similowski et al. [35] showed that diaphragm function in stable eucapnic COPD is not as seriously compromised as was originally thought, since at very high lung volumes the diaphragm of these patients can generate substantially more pressure than the normal diaphragm a higher frac- tion of which is available to inflate the lungs.
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