OBJECTIVES: During mechanical ventilation, air flows may play a role in mucus transport via two-phase gas liquid flow. The aim of this study was to evaluate effects of duty cycles and positive end-expiratory pressure on mucus clearance in pigs using mechanical ventilation, and to assess their safety. DESIGN: Prospective randomized animal study. SETTING: Animal research facility, University of Barcelona, Spain. SUBJECTS: Eight healthy pigs. INTERVENTIONS: Pigs were intubated and on volume-control mechanical ventilation for up to 84 hrs. After 4, 24, 48, and 72 hrs of mechanical ventilation, six levels of duty cycle (0.26, 0.33, 0.41, 0.50, 0.60, and 0.75) with no associated positive end-expiratory pressure or 5 cm H2O of positive end-expiratory pressure were randomly applied. Surgical bed was oriented 30 degrees in the reverse Trendelenburg position, as in the semirecumbent position. MEASUREMENT AND MAIN RESULTS: Inspiratory and expiratory flows and hemodynamics were measured after each 30-min ventilation period. Mucus movement was assessed through fluoroscopy tracking of radio-opaque markers. Mucus velocity was described by a positive vector (toward the glottis) or negative vector (toward the lungs). No effect of positive end-expiratory pressure was found; however, as duty cycle was increasingly prolonged, a trend toward reduced velocity of mucus moving toward the lungs and increased outward mucus velocity was found (p = .064). Two clusters of mucus velocities were identified as duty cycle was prolonged beyond 0.41. Thus, duty cycle >0.41 increased mean expiratory-inspiratory flow bias from -4.1 ± 4.6 to 7.9 ± 5.9 L/min (p < .0001) and promoted outward mucus velocity from -0.22 ± 1.71 mm/min (range, -5.78 to 2.42) to 0.53 ± 1.06 mm/min (-1.91 to 3.88; p = .0048). Duty cycle of 0.75 resulted in intrinsic positive end-expiratory pressure (2.1 ± 1.1 cm H2O [p < .0001] vs. duty cycle 0.26-0.5), with no hemodynamic compromise. CONCLUSIONS: In the semirecumbent position, mucus clearance is improved with prolongation of the duty cycle. However, in clinical practice, positive findings must be balanced against the potentially adverse hemodynamic and respiratory effects. Copyright © 2012 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins.