work of breathing and mechanical ventilation in acute lung injury

Conditions: Acute Lung Injury

Summary: the primary goal of this study is to measure changes in biological markers of inflammation in critically-ill patients with acute lung injury (ali) or acute respiratory distress syndrome (ards) while they are treated with different styles of lung-protective, artificial breathing assistance. secondary goals are to measure the breathing effort of patients using different artificial breathing patterns from the breathing machine. the primary hypothesis is that volume-targeted artificial patterns will produce less inflammation. the secondary hypothesis is that volume-targeted artificial patterns will increase breathing effort compared to pressure-targeted artificial patterns.

ventilator-induced lung injury contributes to the progression of ali/ards,1 and is thought to occur partly from the unequal distribution of a super-normal tidal volume to normal areas of the lung.2 alveolar overdistension causes alveolar-capillary membrane damage,3 increased-permeability pulmonary edema4 and hyaline membrane formation.5 therefore, it is recommended that tidal volume should be reduced to 6-7 ml/kg, and that the peak alveolar pressure, or the end-inspiratory plateau pressure (pplat), should be limited to \< 30 cm h2o.6 the national heart lung and blood institute's ards network demonstrated a 22% reduction in mortality using a "lung-protective" (low tidal volume) ventilation strategy in patients with ali/ards.7 high tidal volume ventilation causes a rapid and substantial increase plasma levels of proinflammatory mediators which decrease in response to lung protective ventilation.8,9 a consequence of lung-protective ventilation is dyspnea and increased work of breathing.10 our recent study11 on work of breathing during lung-protective ventilation found that inspiratory pleural pressure changes were extraordinarily high, averaging 15-17 cm h2o. whereas tidal volume was well controlled during volume ventilation, in contrast, it exceeded target levels in 40% of patients during pressure control ventilation. high tidal volume-high negative pressure ventilation causes acute lung injury in animal models.12,13 thus ventilator-induced lung injury results from excessive stress across lung tissue created by high transpulmonary (airway-pleural).pressure.14 this suggests the possibility that despite pressure control ventilation being set with a low positive airway pressure, "occult" high tidal volume-high transpulmonary pressure ventilation still may occur.11 however, during spontaneous breathing diaphragmatic contractions cause ventilation to be distributed preferentially to dorsal:caudal aspects of the lungs.15 therefore, high transpulmonary pressures created by large negative swings in pleural pressure theoretically may not cause regional lung over-distension and ventilator-induced lung injury if tidal ventilation is preferentially distributed to dorsocaudal lung regions. however, a study16 examining the effects of diaphragmatic breathing during pressure control ventilation found that dorsocaudal distribution of tidal volume was not necessarily improved compared to passive ventilation, as the amount of tidal ventilation distributed to areas of high ventilation/perfusion was unaltered. regardless, during a recent conference on respiratory controversies in the critical care setting, it was noted that the effects of ventilator modes such as volume control, pressure control and airway pressure-release ventilation on proinflammatory cytokine expression during lung-protective ventilation has not been studied in humans.17 thus it is unknown whether or not differences in transpulmonary pressure and tidal volume between these modes has a direct impact on lung inflammation.

Eligibility criteria:
inclusion criteria: * both medical and surgical patients undergoing mechanical ventilatory support who meet criteria for acute lung injury (ali) or acute respiratory distress syndrome (ards) as defined by the european-american consensus conference, * mechanical ventilation via an endotracheal or tracheotomy tube, * pao2/fio2 \< 300 mmhg with bilateral infiltrates on chest radiogram, * clinical management with lung protective ventilation (tidal volume \< 8 ml/kg). exclusion criteria: * patients receiving "comfort care", * high cervical spinal cord injury or other neuromuscular disease, * prisoners, * pregnancy, * less than 18 years of age, * facial fractures and coagulopathies, * patients placed on psychiatric hold.

Keywords: mechanical ventilation