Figure 1:

A summary of 25 years of Acute Respiratory Distress Syndrome (ARDS) intervention trials. Interventions are chronologically displayed with corresponding clinical trials italicized underneath and color-coded to denote clinical efficacy. Interventions that have clear clinical efficacy, in blue boxes, include the use of small tidal volumes,⁹ prone positioning,²⁰ and restrictive fluid administration,³⁷ which have demonstrated clear mortality or ventilator-free days benefits. Interventions in grey boxes include those that have mixed results from different trials, as is the case for conservative oxygen treatment^32,33,75 and early neuromuscular blockade.^38,39 This category (grey boxes) also includes interventions with indeterminate results, such as the case for Positive End Expiratory Pressure (PEEP)¹⁵ – itself is a component of lung-protective ventilation, but the appropriate amount to use is still contended – or those that have value in ARDS patients aside from improving ARDS outcomes, such as early trophic enteral nutrition to prevent gastric intolerance⁴⁰ and Extracorporeal Membrane Oxygenation (ECMO) as a rescue therapy.^35,36 In orange boxes are interventions that failed to demonstrate improvements in ARDS outcomes, such as antifungals, lisofylline, albuterol, simvastatin, vitamin C and vitamin D.^41–47 Dexamethasone is also listed in this category given that the DEXA-ALI trial was conducted in an unblinded fashion²⁸ and prior randomized trials showed no clinical efficacy for steroid administration in ARDS. Methylprednisolone,²⁷ rosuvastatin⁴⁹ and ω−3 Fatty Acids,⁴⁸ listed in red boxes, have shown to cause potential harm in randomized controlled trials. Currently, ongoing or planned trials and emerging therapeutic targets are displayed in green.