Sedation-Ventilation Interaction in Acute Hypoxemic Respiratory Failure: Secondary Analysis of the LANDMARK Trial

Background Ventilation and sedation are used for the management of acute hypoxemic respiratory failure (AHRF), but their optimal combination to minimize the risks of ventilation is not well understood. Research question What are the individual effects and interactions of inspiratory and end-expiratory pressure (PEEP), sedation, and venovenous extracorporeal membrane oxygenation (VV-ECMO) on respiratory drive, effort, and lung-distending pressure in patients with AHRF triggering the ventilator? Study design and methods: Secondary exploratory analysis of a trial of lung and diaphragm protection in AHRF. Inspiratory pressure, sedation, PEEP, and VV-ECMO were titrated while respiratory drive (airway pressure in the first 100 milliseconds, P0.1), effort (esophageal pressure swing, |ΔPes|), and lung-distending pressure (dynamic transpulmonary driving pressure, ΔPL,dyn) were recorded. Associations were evaluated using linear mixed effects regression models including pre-specified terms for potential interactions. Results The study included 223 individual measurements of P0.1 and 235 individual measurements of |ΔPes| and ΔPL,dyn from 30 patients. Propofol attenuated P0.1 (–0.4 cm H2O, 95% CI –0.3, –0.1 per 10 mcg/kg/min increase), |ΔPes| (–2.5 cm H2O, 95% CI –3.4, –1.7 per 10 mcg/kg/min increase) and ΔPL,dyn (–1.6 cm H2O, 95% CI –2.3, –0.8 per 10 mcg/kg/min increase). The effect of inspiratory pressure on |ΔPes| varied depending on propofol dose: with higher propofol dose, inspiratory pressure resulted in higher ΔPL,dyn. Under VV-ECMO, patients (n=16) had significantly lower |ΔPes| (–10 cm H2O, 95% CI –17.5, –2.5) and required less sedation to reduce |ΔPes| than without VV-ECMO (n=14). Interpretation Mechanical ventilation, sedation, and VV-ECMO exert interdependent effects on respiratory drive, effort, and lung-distending pressure in AHRF. Patients under VV-ECMO require less sedation to control respiratory effort.