Table 1.
Summarized results of select, large-scale intervention trials aimed at improving outcomes in patients with Acute Respiratory Distress Syndrome.
| 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% |
| Positive End Expiratory Pressure (PEEP) | Higher vs Lower PEEP (ALVEOLI)15 | Low PEEP or High PEEP (inspiratory plateau pressure of 28–30) | No change in 28-day mortality 31.2% vs. 27.8 (p=0.31) |
| Prone Positioning | Proning Severe ARDS Patients (PROSEVA) trial20 | Supine Position or Prone position (at least 16 hours/day) | Reduction in 28-day mortality 16.0% vs. 32.8% |
| 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 | OXYGEN-ICU trial32 | Conventional oxygen: PaO2 up to 150 mmHg or SaO2 up to 97% to 100% or Conservative Oxygen: PaO2 70 to 100 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)64 | 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 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 (ECMO) | Conventional ventilatory support vs. ECMO for severe adult respiratory failure (CESAR)35 | Conventional Management or ECMO | Increased survival without severe disability at 6 months 63% vs. 47% |
| Rescue Lung Injury in Severe ARDS (EOLIA)36 | Early ECMO or Conventional mechanical ventilation with ECMO 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 (NM) Blockade | ARDS et Curarisation Systematique (ACURASYS)38 | Patients first sedated to a Ramsay sedation score of 6, then given: Placebo or Cisatracurium | Reduction in 90 day mortality 31.6% vs. 40.7% |
| Reevaluation of Systemic Early Neuromuscular Blockade (ROSE)39 | Usual care: lightly sedated or Early NM blockade: deep sedation and cisatracurium | No change in 90-day mortality 41.5% 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 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/hour or Full enteral feeding: 25 to 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 and No change in 60-day mortality 23.2% vs. 22.2% |
| Omega Nutrition Supplement Trial (Omega)48 | Enteral supplementation of n-3 fatty acids, γ-linolenic acid, and antioxidants or An isocaloric control | Reduction in ventilator free days 14.0 vs. 17.2 and Nonstatistical increase in mortality 26.6% vs. 16.3% (p=0.054) | |
| Vitamin C Infusion for Treatment in Sepsis Induced Acute Lung Injury (CITRINS-ALI) 80 | Matched placebo (5% dextrose in water) or Vitamin C 50mg/kg total body weight every 6 hours for 96 hours | No change in SOFA score 3 vs. 3.5 and improved 28-day mortality 29.8% vs. 43.6% | |
| Vitamin D to Improve Outcomes by Leveraging Early Treatment (VIOLET)81 | Placebo or Vitamin D3 | No difference in 90-day mortality 23.5% vs. 20.6% | |
| β2-agonist | Albuterol for the Treatment of ALI (ALTA)42 | Aerosolized albuterol (5 mg) or Placebo (aerosolized saline) | No difference in ventilator free days 14.4 and 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) |