Randomized Feasibility Trial of a Low Tidal Volume-Airway Pressure Release Ventilation Protocol Compared With Traditional Airway Pressure Release Ventilation and Volume Control Ventilation Protocols

OBJECTIVES: Low tidal volume (= tidal volume ≤ 6 mL/kg, predicted body weight) ventilation using volume control benefits patients with acute respiratory distress syndrome. Airway pressure release ventilation is an alternative to low tidal volume-volume control ventilation, but the release breaths generated are variable and can exceed tidal volume breaths of low tidal volume-volume control. We evaluate the application of a low tidal volume-compatible airway pressure release ventilation protocol that manages release volumes on both clinical and feasibility endpoints. DESIGN: We designed a prospective randomized trial in patients with acute hypoxemic respiratory failure. We randomized patients to low tidal volume-volume control, low tidal volume-airway pressure release ventilation, and traditional airway pressure release ventilation with a planned enrollment of 246 patients. The study was stopped early because of low enrollment and inability to consistently achieve tidal volumes less than 6.5 mL/kg in the low tidal volume-airway pressure release ventilation arm. Although the primary clinical study endpoint was Pao(2)/Fio(2) on study day 3, we highlight the feasibility outcomes related to tidal volumes in both arms. SETTING: Four Intermountain Healthcare tertiary ICUs. PATIENTS: Adult ICU patients with hypoxemic respiratory failure anticipated to require prolonged mechanical ventilation. INTERVENTIONS: Low tidal volume-volume control, airway pressure release ventilation, and low tidal volume-airway pressure release ventilation. MEASUREMENTS AND MAIN RESULTS: We observed wide variability and higher tidal (release for airway pressure release ventilation) volumes in both airway pressure release ventilation (8.6 mL/kg; 95% CI, 7.8–9.6) and low tidal volume-airway pressure release ventilation (8.0; 95% CI, 7.3–8.9) than volume control (6.8; 95% CI, 6.2–7.5; p = 0.005) with no difference between airway pressure release ventilation and low tidal volume-airway pressure release ventilation (p = 0.58). Recognizing the limitations of small sample size, we observed no difference in 52 patients in day 3 Pao(2)/ Fio(2) (p = 0.92). We also observed no significant difference between arms in sedation, vasoactive medications, or occurrence of pneumothorax. CONCLUSIONS: Airway pressure release ventilation resulted in release volumes often exceeding 12 mL/kg despite a protocol designed to target low tidal volume ventilation. Current airway pressure release ventilation protocols are unable to achieve consistent and reproducible delivery of low tidal volume ventilation goals. A large-scale efficacy trial of low tidal volume-airway pressure release ventilation is not feasible at this time in the absence of an explicit, generalizable, and reproducible low tidal volume-airway pressure release ventilation protocol.