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.

Abstract

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. 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 PaO2/FIO2 on study day 3, we highlight the feasibility outcomes related to tidal volumes in both arms. Four Intermountain Healthcare tertiary ICUs. Adult ICU patients with hypoxemic respiratory failure anticipated to require prolonged mechanical ventilation. Low tidal volume-volume control, airway pressure release ventilation, and low tidal volume-airway pressure release ventilation. 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 PaO2/ FIO2 (p = 0.92). We also observed no significant difference between arms in sedation, vasoactive medications, or occurrence of pneumothorax. 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.