In this project we will investigate lung mechanics in humans with ARDS in order to develop therapies to improve gas exchange, patient comfort, and ventilatory muscle function. Subproject 1 will describe abnormalities in lung mechanics over time in patients with ARDS and examine correlations among abnormalities of mechanics and gas exchange. Airway resistance, lung and chest wall compliance, mechanical impedance, and work of breathing will be monitored from airflow, volume, airway and esophageal pressure measurements. Respired gases, and arterial blood will be sampled to monitor gas exchange. We will examine similar measures of lung mechanics before and after bronchodilating drugs to test the clinical importance of reversible bronchoconstriction to disordered mechanics, blood oxygenation, and CO2 elimination. Subproject 2 will assess interactions of expiratory effort and PEEP in changing lung volume and gas exchange. While triggering mechanical ventilation, normal subjects will be CO2-driven to hyperventilate as lung volume is tracked by inductance plethysmography. Intra-thoracic pressure and muscle activity will be monitored. The lung volume increments resulting from PEEP will be measured and evidence of attenuation during hyperpnea sought. In patients with acute hypoxemia, lung volume, intra-thoracic pressure and muscle activity will be recorded, as in normals. Hemodynamics and gas exchange will also be monitored before and after sedation and muscle paralysis to determine the mechanisms by which gas exchange is altered by muscle relaxation. Subproject 3 will examine patient- ventilator interactions during ARDS in order: (1) to develop practical bedside measures of the ventilatory capability and workload of spontaneous breathing, thus facilitating ventilator withdrawal, (2) to determine the influence of ventilator mode, machine settings and ventilatory drive on the patient's workload during machine-assisted breathing, and (3) to define the determinants of asynchrony between machine cycling and patient effort. Airway and esophageal pressure-volume plots will be obtained during controlled, assisted, and spontaneous breathing, and work of breathing will be calculated. Pressure-volume and flow information and electromyography will be used to indicate timing differences in patient and ventilator cycles. Apart from its physiologic interest, such data will provide guidelines for selecting the optimal mode and machine settings for patient management.
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