Ventilatory muscle weakness

Infants and children may require long-term ventilatory support due to three categories of diseases that may impair the ventilatory balance increased respiratory load (due to intrinsic cardiopulmonary disorders, upper airway abnormalities, or skeletal deformities), ventilatory muscle weakness [due to neuromuscular diseases (NMD) or spinal cord injury], or failure of neurological control of ventilation (with central hypoventilation syndrome being the most common presentation) (Fig. 1). 

Chemical Abstracts Service Registry Number CAS 93384-43-1. Botulinum toxins comprise a series of seven related protein neurotoxins that prevent fusion of synaptic vesicles with the presynaptic membrane and thus prevent release of acetylcholine. Exposure in a battlefield or terrorist setting would most likely be to inhaled aerosolized toxin. The clinical presentation is that of classical botulism, with descending skeletal muscle weakness (with an intact sensorium) progressing to respiratory paralysis. A toxoid vaccine is available for prophylaxis, and a pentavalent toxoid can be used following exposure its effectiveness wanes rapidly, however, after the end of the clinically asymptomatic latent period. Because treatment is supportive and intensive (involving long-term ventilatory support), the use of botulinum toxin has the potential to overwhelm medical resources especially at forward echelons of care. 

Proper supportive care and administration of antitoxin are the mainstays of current therapy. Patients who present with respiratory failure will need full ventilatory support however, there will be a subgroup of patients who present early without obvious signs of respiratory muscle paralysis. The negative inspiratory force, pulse oximetry, and gag reflex of these patients should be evaluated serially to determine the degree of respiratory muscle weakness and likelihood of impending respiratory failure. 

The respiratory system is responsible for generating and regulating the transpulmonary pressures needed to inflate and deflate the lung. Normal gas exchange between the lung and blood requires breathing patterns that ensure appropriate alveolar ventilation. Ventilatory disorders that alter alveolar ventilation are defined as hypoventilation or hyperventilation syndromes. Hyperventilation results in an increase in the partial pressure of arterial CO2 above normal limits and can lead to acidosis, pulmonary hypertension, congestive heart failure, headache, and disturbed sleep. Hypoventilation results in a decrease in the partial pressure of arterial CO2 below normal limits and can lead to alkalosis, syncope, epileptic attacks, reduced cardiac output, and muscle weakness. 

Santiago RM, Scharnhorst D, Ratkin G, et al. Respiratory muscle weakness and ventilatory failure in AL amyloidosis with muscular pseudohypertrophy. Am J Med 1987 83(1) 175-178. 

FIGURE 11.4 (a) Optimal waveforms for respiratory muscle driving pressure, P(t) respiratory airflow, V and respired volume, R, during normal breathing (NL) or under various types of ventilatory loads IRL and ERL, inspiratory and expiratory resistive load lEL and CEL, inspiratory and continuous elastic load, (b) Optimal waveforms for P(t) under increasing respiratory muscle fatigue (amplitude limited upper panel) and muscle weakness (rate limited lower panel). (From Poon and coworkers [1992]. With permission.)... 

Other metabolic factors contributing to PMV include hypophosphatemia and hypomagnesemia, both of which have been associated with diminished diaphragmatic function. Hypothyroidism is an uncommon cause of ventilator dependency (27), being associated with respiratory muscle weakness as well as altered ventilatory drive and upper airway obstruction. Hypothyroidism is a potentially treatable cause of failure to wean and it should be considered in patients with prolonged ventilator dependence. 

Only a small proportion of patients fail to wean from mechanical ventilation, but they require a disproportionate amount of resources. Weaning failure has been extensively studied in the clinical literature and several factors are likely to contribute to it. These factors include inadequate ventilatory drive, respiratory muscle weakness, respiratory muscle fatigue, increased work of breathing, or cardiac failure. There is accumulating... 

Patients with copathology contributing to ventilatory failure, e.g., thoracoplasty, respiratory muscle weakness, mmbid obesity... 

Mechanical ventilation is associated with several complications including respiratory muscle weakness, ventilator-induced lung injury, trauma to the upper airway, and ventilator-associated pneumonia (14,15). Therefore, minimizing the duration of invasive ventilatory... 

Ventilatory impairment results from inspiratory muscle weakness, central hypoventilation, thoracic restriction, upper airway narrowing, extreme obesity, abdominal distension, and improperly fitting thoracolumbar orthoses. In NMD, pulmonary infiltrates and respiratory failure are precipitated by mucus plugging due to an ineffective secretion clearance, especially during acute respiratory infections (2,7). 

Exercise limitation and functional disability in COPD have a complex, multifactorial basis. Ventilatory limitation is caused by increased airways resistance, static and dynamic hyperinflation, increased elastic load to breathing, gas exchange disturbances, and mechanical disadvantage and/or weakness of the respiratory muscles (4-6). Car-diocirculatory disturbances (7,8), nutritional factors (9), and psychological factors, such as anxiety and fear, also contribute commonly to exercise intolerance. Skeletal muscle dysfunction is characterized by reductions in muscle mass (10,11), atrophy of type I (slow twitch, oxidative, endurance) (12,13) and type Ila (fast twitch) muscle fibers (14), altered myosin heavy chain expression (15), as well as reductions in fiber capillarization (16) and oxidative enzyme capacity (17,18). Such a dysfunction is another key factor that contributes... 

Poon et al. (1992) have shown that the dynamic optimization model predicts closely the Pnius(0 trajectories under various conditions of ventilatory loading as well as respiratory muscle fatigue and weakness (Figure 20.4). In addition, the model also accurately predicts the ventilatory and breathing pattern... 

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