Table 1.

Summary of Randomized Controlled Trials of Therapies for ARDS and Corresponding Heterogeneity of Treatment Effects

Therapy	Noteworthy Trial Findings	Heterogeneity of Treatment Effect
Lung-protective ventilation	ARMA: Lower mortality with LPV5	None identified6,7
Open lung ventilation	ALVEOLI: No difference in hospital mortality8 ExPress: No difference in 28-d mortality9 LOVS: No difference in 28-d hospital mortality10 ART: Higher 28-d mortality with open lung ventilation11	Open lung ventilation associated with lower mortality in: Pao2/Fio2 ratio ≤ 200 mm Hg12 PEEP responders with improved Pao2/Fio2 ratio13,14 PEEP responders with lower driving pressure15 Hyperinflammatory phenotype16 Open lung ventilation associated with higher mortality in patients with pneumonia requiring vasopressors17
HFOV	OSCILLATE: Higher hospital mortality with HFOV18 OSCAR: No difference in 30-d mortality19	HFOV associated with lower mortality in patients with a Pao2/Fio2 ratio < 100 mm Hg (or < 64 mm Hg)20
Prone positioning	PROSEVA: Lower 28-d mortality with prone positioning21	Mortality benefit limited to a Pao2/Fio2 ratio < 150 mm Hg21
NMBA	ACURASYS: Lower adjusted 90-d mortality with NMBA22 ROSE: No difference in 90-d mortality23	NMBA associated with lower mortality in: Pao2/Fio2 ratio <150 mm Hg22
Fluid therapy	FACTT: No difference in mortality; more VFDs with conservative fluid strategy24	Liberal fluid strategy associated with higher mortality in hyperinflammatory phenotype25 Liberal fluid strategy associated with lower mortality in less inflammatory phenotype
Statins	HARP-2: No difference in 28-d mortality with simvastatin26 SAILS: No difference in 60-d or hospital mortality with rosuvastatin27	Simvastatin associated with lower mortality in: Hyperinflammatory phenotype28 Lower APACHE II score29 Statins associated with lower mortality in sepsis-related ARDS with a Pao2/Fio2 ratio < 100 mm Hg30 Simvastatin associated with higher mortality in higher APACHE II score29 None identified for rosuvastatin31

ACURASYS = ARDS et Curarisation; ALVEOLI = Assessment of Low Tidal Volume and Elevated End-Expiratory Pressure to Obviate Lung Injury; APACHE II = Acute Physiology and Chronic Health Evaluation II; ARMA = Ventilation with Lower Tidal Volumes as Compared with Traditional Tidal Volumes for Acute Lung Injury and Acute Respiratory Distress Syndrome; ExPress = Expiratory Pressure Study; FACTT = Fluids and Catheters Treatment Trial; HARP-2 = Hydroxymethylglutaryl-CoA Reductase Inhibition in Acute Lung Injury to Reduce Pulmonary Inflammation 2; HFOV = high-frequency oscillatory ventilation; LOVS = Lung Open Ventilation Study; NMBA = neuromuscular blocking agent; OSCAR = Oscillation in ARDS; PEEP = positive end-expiratory pressure; PROSEVA = Effect of Prone Positioning on Mortality in Patients with Severe Acute Respiratory Distress Syndrome; ROSE = Reevaluation of Systemic Early Neuromuscular Blockade; SAILS = Statins for Acutely Injured Lungs from Sepsis; VFD = ventilator-free days.