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patients. Ventilatory support reductionrelated changes in transdiaphragmatic pressure, respiratory rate, and thoracoabdominal dyssynchrony are clearly not specific manifestations of respiratory muscle fatigue.55–60 The most promising diagnostic test of diaphragm contractility to date is the transdiaphragmatic pressure measurement during twitch stimulation of the phrenic nerves.21,61 However, too few patients have been studied with this technique to draw any meaningful conclusions about the prevalence of diaphragm fatigue that is attributable to ventilator dependence. The load on the ventilatory muscles is a function of ventilation demands and respiratory system mechanics (ie, primarily compliance and resistance). Normal minute ventilation during spontaneous breathing is generally 10 L/min, normal respiratory system compliance (ie, tidal volume/static inflation pressure) is generally 50–100 mL/cm H2O, and normal airway resistance (ie, peak-static inflation pressure/constant inspiratory flow) is generally 5–15 cm H2O/L/s. Ventilation demands can increase as a consequence of increased oxygen demands in patients with sepsis or increased dead space in patients with obstructive diseases. Compliance worsening can be a consequence of lung edema, infection, inflammation, or fibrosis, and of chest wall abnormalities such as edema or surgical dressings. Resistance worsening can be a consequence of bronchoconstriction and airway inflammation. Additional load can also be imposed by narrow endotracheal tubes and by insensitive or poorly responsive ventilator demand valves. The load imposed by ventilation demands interacting with respiratory system mechanics can be expressed as respiratory work, pressure time integral, or the change in metabolism (eg, the oxygen cost attributable to breathing). Many studies19,35,62–66 show that patients who are ventilator-dependent tend to have larger respiratory muscle loads than do patients who can be withdrawn from mechanical ventilation. In patients with airways obstruction, the load imposed by dynamic hyperinflation has received particular attention as an important contributor to ventilator depenTable 2. Causes of Ventilator Dependency Causes Description Neurologic controller Central drive; peripheral nerves Respiratory system Mechanical loads: respiratory system mechanics; imposed loading Ventilatory muscle properties: inherent strength/endurance; metabolic state/nutrients/oxygen delivery and extraction Gas exchange properties: vascular properties and ventilation/perfusion matching Cardiovascular system Cardiac tolerance of ventilatory muscle work; peripheral oxygen demands Psychological issues EVIDENCE-BASED GUIDELINES FOR WEANING AND DISCONTINUING VENTILATORY SUPPORT RESPIRATORY CARE • JANUARY 2002 VOL 47 NO 1 71 dence.23,33,65,67–71 As is true for measures of ventilatory pump capacity, however, most investigators report considerable overlap in load parameters between patients with different discontinuation outcomes. Patients who go on to fail to respond to ventilator withdrawal attempts because of a capacity/load imbalance tend to display rapid, shallow breathing patterns.2,72,73 This pattern is advantageous from an energetics perspective, but it is also associated with increased dead space and wasted ventilation and, hence with impaired carbon dioxide elimination. Chemoreceptive and mechanoreceptive feedback into the neural control of breathing is not well understood, and thus it is difficult to distinguish whether this breathing pattern is a consequence of a reduced respiratory drive per breath or an inability of ventilatory muscles to respond to an appropriately increased neural stimulus.19,62,65,71,72 Metabolic Factors and Ventilatory Muscle Function: Nutrition, electrolytes, hormones, and oxygen transport are all metabolic factors that can affect ventilatory muscle function. Inadequate nutrition leads to protein catabolism and loss of muscle performance.74,75 The normal hypoxic ventilatory response and the hypercapnic ventilatory response also have been shown to deteriorate under conditions of semistarvation.76 In contrast, overfeeding also