Clinical Intervention |
Trial Name |
Study Groups |
Outcomes |
Small tidal volumes |
The 2000 Acute Respiratory Distress Syndrome Network trial (ARMA)9 |
Low tidal volume (6 ml/kg of predicted body weight) or Traditional tidal volume (12 ml/kg of predicted body weight) |
Reduction in 180-day mortality 31.0% vs. 39.8% (P = 0.007) |
PEEP |
Higher vs. Lower PEEP (ALVEOLI)15 |
Low PEEP or High PEEP (inspiratory plateau pressure of 28–30) |
No change in death before discharge 24.9% vs. 27.5% (P = 0.48) |
Prone positioning |
Proning Severe ARDS Patients (PROSEVA) trial20 |
Supine position or Prone position (at least 16 h/day) |
Reduction in 28-day mortality 16.0% vs. 32.8% (P < 0.001) |
Steroids |
Late Steroid Rescue Study (LaSRS)27 |
In patients 7–28 days after onset of ARDS: Placebo or Methylprednisolone |
No change in 60-day mortality 28.6% vs. 29.2% and Increased mortality in patients receiving methylprednisolone at least 14 days after ARDS diagnosis |
|
Dexamethasone Treatment for the Acute Respiratory Distress Syndrome (DEXA-ARDS)28 |
Standard of care or Dexamethasone |
Increase in ventilator-free days 12.3 vs. 7.5 days (P < 0.0001) and Reduction in all-cause mortality at day 60 21% vs. 36% |
Conservative oxygenation |
Normal Oxygenation Versus Hyperoxia in the Intensive Care Unit (ICU) (OXYGEN-ICU) trial32 |
Conventional oxygen: PaO2 up to 150 mmHg or SaO2 up to 97 to 100% or Conservative oxygen: PaO2 70 to 100 mmHg or SaO2 of 94 to 98% |
Reduction in ICU mortality 11.6% vs. 20.2% (P = 0.01) |
|
Intensive Care Unit Randomized Trial Comparing Two Approaches to Oxygen Therapy (ICU-ROX)75 |
Usual oxygen therapy: no upper limit to FIO2 or SaO2 or Conservative oxygen therapy: SaO2 between 90 and 97% |
No change in ventilator-free days 21.3 vs. 22.1 days and No change in 180-day mortality 35.7% vs. 34.5% |
|
Liberal or Conservative Oxygen Therapy for ARDS (LOCO2)33 |
Liberal oxygenation: target PaO2 90–105 mmHg; SaO2 > 96% or Conservative oxygenation: target PaO2 55–70 mmHg; SaO2 88–92% |
Increased mortality in conservative oxygen group 34.3% vs. 26.5% |
Extracorporeal membrane oxygenation |
Conventional Ventilatory Support vs. ECMO for Severe Adult Respiratory Failure (CESAR)35 |
Conventional management or Extracorporeal membrane oxygenation |
Increased survival without severe disability at 6 months 63% vs. 47% |
|
Rescue Lung Injury in Severe ARDS (EOLIA)36 |
Early extracorporeal membrane oxygenation or Conventional mechanical ventilation with extracorporeal membrane oxygenation as a rescue therapy |
Non–statistically significant reduction in mortality 35% vs. 46% (P = 0.09) |
Fluid restriction |
Fluids and Catheters Treatment Trial (FACTT)37 |
Liberal fluids (CVP 10–14) or Conservative fluids (CVP < 4) |
No change in all-cause mortality at 60 days 25.5% vs. 28.4% (P = 0.30) |
Early neuromuscular blockade |
ARDS et Curarisation Systematique (ACURASYS)38 |
Patients first sedated to a Ramsay sedation score of 6, then given: Placebo or Cisatracurium |
Adjusted hazard ratio for death at 90 days of 0.68 in NM blockade group (P = 0.04) |
|
Reevaluation of Systemic Early Neuromuscular Blockade (ROSE)39 |
Usual care: lightly sedated or Early neuromuscular blockade: deep sedation and cisatracurium |
No change in 90-day mortality 42.5% vs. 42.8% |
Statin treatment |
Simvastatin in the Acute Respiratory Distress Syndrome (HARP-2)47 |
Placebo or Simvastatin for maximum 28 days |
No significant change in ventilator-free days 12.6 vs. 11.5 days or 28-day mortality 22% vs. 26.8% |
|
Statins for Acutely Injured Lungs from Sepsis (SAILS)49 |
Placebo or Rosuvastatin for maximum 28 days |
No change in 60-day mortality 28.5% vs. 24.9% and Fewer days free of renal or hepatic failure |
Vitamins, nutrition, and supplements |
Early vs. Delayed Enteral Nutrition (EDEN)40 |
Trophic enteral feeding: 10–20 kcal/h or Full enteral feeding: 25–30 kcal/kg per day of nonprotein calories and 1.2 to 1.6 g/kg per day of protein |
No change in ventilator-free days 14.9 vs. 15 days and No change in 60-day mortality 23.2% vs. 22.2% |
|
Omega Nutrition Supplement Trial (Omega)48 |
Enteral supplementation of omega-3 fatty acids, γ-linolenic acid, and antioxidants or An isocaloric control |
Reduction in ventilator-free days 14.0 vs. 17.2 days and Non-statistically significant increase in mortality 26.6% vs. 16.3% (P = 0.054) |
|
Vitamin C Infusion for Treatment in Sepsis Induced Acute Lung Injury (CITRIS-ALI)76 |
Matched placebo (5% dextrose in water) or Vitamin C 50 mg/kg total body weight every 6 h for 96 h |
No change in Sequential Organ Failure Assessment (SOFA) score 3 vs. 3.5 |
|
Vitamin D to Improve Outcomes by Leveraging Early Treatment (VIOLET)77 |
Placebo or Vitamin D3 |
No difference in 90-day mortality 23.5% vs. 20.6% (P = 0.26) |
β2-Agonist |
Albuterol for the Treatment of ALI (ALTA)41 |
Aerosolized albuterol (5 mg) or Placebo (aerosolized saline) |
No difference in ventilator-free days 14.4 vs. 16.6 and No difference in mortality before hospital discharge 23% vs. 17.7% |
Antifungals |
Ketoconazole for ALI/ARDS (KARMA)46 |
Ketoconazole, 400 mg/day or Placebo |
No difference in in-hospital mortality 34.1% vs. 35.2% |
Lisofylline |
Lisofylline for ALI/ARDS (LARMA)45 |
Lisofylline (3 mg/kg with a maximum dose of 300 mg) or Placebo |
No difference in mortality 31.9% vs. 24.7% (P = 0.215) |