Sections

General

1. Semler. Oxygen-Saturation Targets for Critically Ill Adults Receiving Mechanical Ventilation. N Engl J Med 2022;epublished October 24th
2. Gelissen. Effect of Low-Normal vs High-Normal Oxygenation Targets on Organ Dysfunction in Critically Ill Patients. A Randomized Clinical Trial. JAMA 2021;epublished August 31st
3. Schjørring. Lower or Higher Oxygenation Targets for Acute Hypoxemic Respiratory Failure (HOT-ICU). N Engl J Med 2021;epublished January 20th
4. Barrot. Liberal or conservative oxygen therapy for acute respiratory distress syndrome (LOCO2). N Engl J Med 2020;​382:​999-1008
5. The ICU-ROX Investigators. Conservative Oxygen Therapy during Mechanical Ventilation in the ICU. N Engl J Med 2020;382:989-998
6. Girardis. Effect of Conservative vs Conventional Oxygen Therapy on Mortality Among Patients in an Intensive Care Unit. The Oxygen-ICU Randomized Clinical Trial. JAMA 2016;316(15):1583-1589
7. Panwar. Conservative versus liberal oxygenation targets for mechanically ventilated patients: a pilot multicenter randomized
   controlled trial (CLOSE). Am J Respir Crit Care Med 2016;​193:​43-51

Post Cardiac Arrest

1. Bernard. Effect of Lower vs Higher Oxygen Saturation Targets on Survival to Hospital Discharge Among Patients Resuscitated After Out-of-Hospital Cardiac Arrest. The EXACT Randomized Clinical Trial. JAMA 2022;epublished October 26th
2. Kjaergaard. Blood-Pressure Targets in Comatose Survivors of Cardiac Arrest. N Engl J Med 2022;epublished August 27th

Trauma

• Arleth. Early Restrictive vs Liberal Oxygen for Trauma Patients. The TRAUMOX2 Randomized Clinical Trial. JAMA 2024;epublished December 10th

COVID-19

1. Nielsen. Lower vs Higher Oxygenation Target and Days Alive Without Life Support in COVID-19. The HOT-COVID Randomized Clinical Trial. JAMA 2024;epublished March 19th

Perioperatively

1. Mayhoff. Increased Long-Term Mortality After a High Perioperative Inspiratory Oxygen Fraction During Abdominal Surgery: Follow-Up of a Randomized Clinical Trial. Anesth Analg 2012.
2. Meyhoff. Effect of High Perioperative Oxygen Fraction on Surgical Site Infection and Pulmonary Complications After Abdominal Surgery. The PROXI Randomized Clinical Trial. JAMA 2009;302(14):1543-1550

Paediatrics

1. Peters. Conservative versus liberal oxygenation targets in critically ill children (Oxy-PICU): a UK multicentre, open, parallel-group, randomised clinical trial. Lancet 2023;epublished December 1st
2. Maitland. Randomised controlled trial of oxygen therapy and high-flow nasal therapy in African children with pneumonia (COAST trial). Intensive Care Med 2021;47:566–576
3. Cunningham. Oxygen saturation targets in infants with bronchiolitis (BIDS): a double-blind, randomised, equivalence trial. Lancet 2015;386(9998):1041–1048

ARDS

1. Villar. The ALIEN study: incidence and outcome of acute respiratory distress syndrome in the era of lung protective ventilation. Intensive Care Med 2011; epub ahead of print.    (Erratum)
2. Terragni. Tidal hyperinflation during low tidal volume ventilation in acute respiratory distress syndrome. Am J Respir Crit Care Med 2007;175:160–166
3. Villar. A high positive end-expiratory pressure, low tidal volume ventilatory strategy improves outcome in persistent acute respiratory distress syndrome: a randomized, controlled trial (AIRES Study). Crit Care Med 2006; 34:1311-1318
4. The Acute Respiratory Distress Syndrome Network. Ventilation with Lower Tidal Volumes as Compared with Traditional Tidal Volumes for Acute Lung Injury and the Acute Respiratory Distress Syndrome. N Engl J Med 2000; 342:1301-1308
5. Brower. Prospective, randomized, controlled clinical trial comparing traditional versus reduced tidal volume ventilation in acute respiratory distress syndrome patients. Crit Care Med 1999;27:1492-1498
6. Stewart. Evaluation of a ventilation strategy to prevent barotrauma in patients at high risk for acute respiratory distress syndrome. Pressure- and Volume-Limited Ventilation Strategy Group. N Engl J Med 1998;338:355-361.
7. Amato. Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med 1998; 338:347-354.
8. Brochard. Tidal volume reduction for prevention of ventilator-induced lung injury in acute respiratory distress syndrome. The Multicenter Trial Group on Tidal Volume Reduction in ARDS. Am J Respir Crit Care Med 1998; 158:1831-1838

Non-ARDS

1. Writing Group for the PReVENT Investigators. Effect of a Low vs Intermediate Tidal Volume Strategy on Ventilator-Free Days in Intensive Care Unit Patients Without ARDSA Randomized Clinical Trial. JAMA 2018;epublished October 24th
2. Determann. Ventilation with lower tidal volumes as compared with conventional tidal volumes for patients without acute lung injury: a preventive randomized controlled trial. Crit Care. 2010;14(1):R1

Intra-Operative

1. Ferrando. Individualised, perioperative open-lung ventilation strategy during one-lung ventilation (iPROVE-OLV): a multicentre, randomised, controlled clinical trial. Lancet Respir Med 2023;epublished December 5th
2. Writing Committee for the PROBESE Collaborative Group of the PROtective VEntilation Network (PROVEnet) for the Clinical Trial Network of the European Society of Anaesthesiology. Effect of Intraoperative High Positive End-Expiratory Pressure (PEEP) With Recruitment Maneuvers vs Low PEEP on Postoperative Pulmonary Complications in Obese Patients. A Randomized Clinical Trial. JAMA 2019;epublished June 3rd
3. Ferrando. Individualised perioperative open-lung approach versus standard protective ventilation in abdominal surgery (iPROVE): a randomised controlled trial. Lancet Respir Med 2018;epublished January 19th
4. Futier. A Trial of Intraoperative Low-Tidal-Volume Ventilation in Abdominal Surgery (IMPROVE study). N Engl J Med 2013; 369:428-437

ARDS

1. Briel. Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis. JAMA 2010;303(9):865-73
2. Mercat. Positive End-Expiratory Pressure Setting in Adults With Acute Lung Injury and Acute Respiratory Distress Syndrome. JAMA. 2008;299(6):646-655.
3. Meade. Ventilation strategy using low tidal volumes, recruitment maneuvers, and high positive end-expiratory pressure for acute lung injury and acute respiratory distress syndrome: A randomized controlled trial. JAMA 2008; 299:637-645.
4. The National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. Higher versus Lower Positive End-Expiratory Pressures in Patients with the Acute Respiratory Distress Syndrome. N Engl J Med 2004;351:327-36

Oesophageal Pressure Monitor Guided

1. Beitler. Effect of Titrating Positive End-Expiratory Pressure (PEEP) With an Esophageal Pressure–Guided Strategy vs an Empirical High PEEP-Fio2 Strategy on Death and Days Free From Mechanical Ventilation Among Patients With Acute Respiratory Distress Syndrome (EPVent-2). A Randomized Clinical Trial. JAMA 2019;321(9):846-857
2. Talmor  D, Sarge  T, Malhotra  A,  et al.  Mechanical ventilation guided by esophageal pressure in acute lung injury.  N Engl J Med 2008;359(20):2095-2104

1. The National Heart, Lung, and Blood Institute PETAL Clinical Trials Network. Early Neuromuscular Blockade in the Acute Respiratory Distress Syndrome (ROSE trial). N Engl J Med 2019;epublished May 19th
2. Papazian. Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med 2010;363:1107-1116  

1. ART Trial Investigators Writing Group. Effect of Lung Recruitment and Titrated Positive End-Expiratory Pressure (PEEP) vs Low PEEP on Mortality in Patients With Acute Respiratory Distress Syndrome. A Randomized Clinical Trial (ART). JAMA 2017;epublished September 27th
2. Leme. Effect of Intensive vs Moderate Alveolar Recruitment Strategies Added to Lung-Protective Ventilation on Postoperative Pulmonary Complications. A Randomized Clinical Trial. JAMA 2017;epublished March 21st

1. Combes. Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome (EOLIA Trial). N Engl J Med 2018;378:1965-75
   • Goligher. Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome and Posterior Probability of Mortality Benefit in a Post Hoc Bayesian Analysis of a Randomized Clinical Trial (EOLIA). JAMA 2018;epublished October 22nd
2. Peek. Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial. Lancet 2009; 374: 1351-63

1. McNamee. Effect of Lower Tidal Volume Ventilation Facilitated by Extracorporeal Carbon Dioxide Removal vs Standard Care Ventilation on 90-Day Mortality in Patients With Acute Hypoxemic Respiratory Failure. The REST Randomized Clinical Trial. JAMA 2021;epublished August 31st
2. Morris.. Randomized clinical trial of pressure-controlled inverse ratio ventilation and extracorporeal CO₂ removal for adult respiratory distress syndrome. Am J Respir Crit Care Med 1994;149(2):295-305

1. Ferguson. High-Frequency Oscillation in Early Acute Respiratory Distress Syndrome (OSCILLATE). New Engl J Med 2013;epublished January 22rd
2. Young. High-Frequency Oscillation for Acute Respiratory Distress Syndrome (OSCAR). New Engl J Med 2013;epublished January 22nd
3. Bollen. High frequency oscillatory ventilation compared with conventional mechanical ventilation in adult respiratory distress syndrome: a randomized controlled trial. Crit Care 2005; 9(4): R430–R439
4. Derdak. High-frequency oscillatory ventilation for acute respiratory distress syndrome in adults (MOAT Study). Am J Respir Crit Care Med 2002; 166: 801–8

1. Lalgudi Ganesan. Airway Pressure Release Ventilation in Pediatric Acute Respiratory Distress Syndrome. A Randomized Controlled Trial. Am J Respir Crit Care Med 2018;198(9):1199-1207
2. Zhou. Early application of airway pressure release ventilation may reduce the duration of mechanical ventilation in acute respiratory distress syndrome. Intensive Care Med 2017;epublished September 22nd

1. Demoule. Neurally adjusted ventilatory assist as an alternative to pressure support ventilation in adults: a French multicentre randomized trial. Intensive Care Med 2016;epublished September 30th

1. Kacmarek. Partial Liquid Ventilation in Adult Patients with Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med. 2006 Sep 1;174(5):615
2. Hirschl. Prospective, Randomized, Controlled Pilot Study of Partial Liquid Ventilation in Adult Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med 2002;165:781-787

1. RENOVATE Investigators and the BRICNet Authors. High-Flow Nasal Oxygen vs Noninvasive Ventilation in Patients With Acute Respiratory Failure. The RENOVATE Randomized Clinical Trial. JAMA 2024;epublished December 11th
2. Azoulay. Effect of High-Flow Nasal Oxygen vs Standard Oxygen on 28-Day Mortality in Immunocompromised Patients With Acute Respiratory Failure: The HIGH Randomized Clinical Trial. JAMA 2018;epublished October 24th
3. Makdee. High-Flow Nasal Cannula Versus Conventional Oxygen Therapy in Emergency Department Patients With Cardiogenic Pulmonary Edema: A Randomized Controlled Trial. Ann Emerg Med 2017;epublished June 7th
4. Roberts. Nasal High-Flow Therapy for Primary Respiratory Support in Preterm Infants (HIPSTER Trial). N Engl J Med 2016;375:1142-1151
5. Jones. Randomized Controlled Trial of Humidified High-Flow Nasal Oxygen for Acute Respiratory Distress in the Emergency Department: The HOT-ER Study. Respir Care 2015;epublished November 17th
6. Frat. High-Flow Oxygen through Nasal Cannula in Acute Hypoxemic Respiratory Failure (FLORALI study). N Eng J Med 2015;epublished May 17th
7. Stéphan. High-Flow Nasal Oxygen vs Noninvasive Positive Airway Pressure in Hypoxemic Patients After Cardiothoracic Surgery: A Randomized Clinical Trial. JAMA 2015;epublished May 17th

1. George. Effectiveness of nasal high-flow oxygen during apnoea on hypoxaemia and intubation success in paediatric emergency and ICU settings: a randomised, controlled, open-label trial. Lancet Respir Med 2025;epublished March 21st
2. Jaber. Apnoeic oxygenation via high-flow nasal cannula oxygen combined with non-invasive ventilation preoxygenation for intubation in hypoxaemic patients in the intensive care unit: the single-centre, blinded, randomised controlled OPTINIV trial. Intensive Care Med 2016;epublished October 11th

1. Fernandez. High-flow nasal cannula to prevent postextubation respiratory failure in high-risk non-hypercapnic patients: a randomized multicenter trial. Annals of Intensive Care 2017;7:47
2. Hernández. Effect of Postextubation High-Flow Nasal Cannula vs Noninvasive Ventilation on Reintubation and Postextubation Respiratory Failure in High-Risk PatientsA Randomized Clinical Trial. JAMA 2016;epublished October 5th
3. Futier. Effect of early postextubation high-flow nasal cannula vs conventional oxygen therapy on hypoxaemia in patients after major abdominal surgery: a French multicentre randomised controlled trial (OPERA). Intensive Care Med 2016;epublished October 22nd
4. Hernández. Effect of Postextubation High-Flow Nasal Cannula vs Conventional Oxygen Therapy on Reintubation in Low-Risk Patients. A Randomized Clinical Trial. JAMA 2016;epublished March 15th
5. Corley. Direct extubation onto high-flow nasal cannulae post-cardiac surgery versus standard treatment in patients with a BMI ≥30: a randomised controlled trial. Intensive Care Med 2015;epublished April 8th

1. George. Effectiveness of nasal high-flow oxygen during apnoea on hypoxaemia and intubation success in paediatric emergency and ICU settings: a randomised, controlled, open-label trial. Lancet Respir Med 2025;epublished March 21st
2. Milési. A multicenter randomized controlled trial of a 3-L/kg/min versus 2-L/kg/min high-flow nasal cannula flow rate in young infants with severe viral bronchiolitis (TRAMONTANE 2). Intensive Care Med 2018;epublished October 21st

1. The National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network. Initial Trophic vs Full Enteral Feeding in Patients With Acute Lung Injury: The EDEN Randomized Trial. JAMA 2012;epublished February 5th

1. Rice. Enteral Omega-3 Fatty Acid, γ-Linolenic Acid, and Antioxidant Supplementation in Acute Lung Injury. JAMA 2011;306(14):1574-1581 
2. Stapleton. A phase II randomized placebo-controlled trial of omega-3 fatty acids for the treatment of acute lung injury. Crit Care Med. 2011;39(7):1655-62

1. Jabaudon. Inhaled Sedation in Acute Respiratory Distress SyndromeThe SESAR Randomized Clinical Trial. JAMA 2025;epublished March 18th

• Dadam. The Effect of Reconnection to Mechanical Ventilation for 1 Hour After Spontaneous Breathing Trial on Reintubation Among Patients Ventilated for More Than 12 Hours. A Randomized Clinical Trial. Chest 2021;160(1):148-156
• Fernandez. Reconnection to mechanical ventilation for 1 h after a successful spontaneous breathing trial reduces reintubation in critically ill patients: a multicenter randomized controlled trial. Intensive Care Med 2017;epublished September 22nd

• Perkins. Effect of Protocolized Weaning With Early Extubation to Noninvasive Ventilation vs Invasive Weaning on Time to Liberation From Mechanical Ventilation Among Patients With Respiratory Failure. The Breathe Randomized Clinical Trial. JAMA 2018;epublished October 22nd

• Jaber. Effect of Noninvasive Ventilation on Tracheal Reintubation Among Patients With Hypoxemic Respiratory Failure Following Abdominal Surgery: A Randomized Clinical Trial (NIVAS). JAMA 2016;epublished March 15th

• Young. Effect of Early vs Late Tracheostomy Placement on Survival in Patients Receiving Mechanical Ventilation: The TracMan Randomized Trial. JAMA 2013;309(20):2121
• Terragni. Early vs late tracheotomy for prevention of pneumonia in mechanically ventilated adult ICU patients. JAMA 2010;303:1483–1489
• Blot. Early tracheotomy versus prolonged endotracheal intubation in unselected severely ill ICU patients. Intensive Care Med 2008;34(10):1779-1787
• Rumbak. A prospective, randomized, study comparing early percutaneous dilational tracheotomy to prolonged translaryngeal intubation (delayed tracheotomy) in critically ill medical patients. Crit Care Med 2004;32:1689–1694

1. Gobatto. Ultrasound-guided percutaneous dilational tracheostomy versus bronchoscopy-guided percutaneous dilational tracheostomy in critically ill patients (TRACHUS): a randomized noninferiority controlled trial. Intensive Care Med 2016;epublished February 1st

Corticosteroids

• Blum. Adjunct prednisone therapy for patients with community-acquired pneumonia: a multicentre, double-blind, randomised, placebo-controlled trial. Lancet 2015;385(9977):1511–1518
• Torres. Effect of Corticosteroids on Treatment Failure Among Hospitalized Patients With Severe Community-Acquired Pneumonia and High Inflammatory Response. A Randomized Clinical Trial. JAMA 2015;313(7):677-686

Selective Digestive Decontamination

• The SuDDICU Investigators for the Australian and New Zealand Intensive Care Society Clinical Trials Group. Effect of Selective Decontamination of the Digestive Tract on Hospital Mortality in Critically Ill Patients Receiving Mechanical Ventilation. A Randomized Clinical Trial. JAMA 2022;epublished October 26th

Tracheal Cuff Pressure

• Dat. Effectiveness of continuous endotracheal cuff pressure control for the prevention of ventilator associated respiratory infections: an open-label randomised, controlled trial. Clin Infect Dis 2021;epublished August 22nd
• Marjanovic. Continuous Pneumatic Regulation of Tracheal Cuff Pressure to Decrease Ventilator-associated Pneumonia in Trauma Patients Who Were Mechanically Ventilated. The AGATE Multicenter Randomized Controlled Study. Chest 2021;160(2):499-508

Miscellaneous

• Bassi. Randomized, multicenter trial of lateral Trendelenburg versus semirecumbent body position for the prevention of ventilator-associated pneumonia. Intensive Care Med 2017;epublished June 20th
• Seguin. Effect of Oropharyngeal Povidone-Iodine Preventive Oral Care on Ventilator-Associated Pneumonia in Severely Brain-Injured or Cerebral Hemorrhage Patients: A Multicenter, Randomized Controlled Trial (SPIRIT study). Crit Care Med 2014;42(1):1-8
• Papazian. Effect of Statin Therapy on Mortality in Patients With Ventilator-Associated PneumoniaA Randomized Clinical Trial. JAMA 2013;310(16):1692-1700

Pleural Lysis

• Rahman. Intrapleural Use of Tissue Plasminogen Activator and DNase in Pleural Infection. N Engl J Med 2011; 365:518-526

1. Bowdish. A Randomized Trial of Mesenchymal Stromal Cells for Moderate to Severe ARDS From COVID-19. Am J Respir Crit Care Med 2022;epublished September 13th

1. McAuley. Simvastatin in ARDS. New Engl J Med 2014;epublished September 30th
2. The National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. Rosuvastatin for Sepsis-Associated Acute Respiratory Distress Syndrome (SAILS). New Engl J Med 2014;epublished May 18th

1. van Meenen. Effect of On-Demand vs Routine Nebulization of Acetylcysteine With Salbutamol on Ventilator-Free Days in Intensive Care Unit Patients Receiving Invasive Ventilation (NEBULAE). A Randomized Clinical Trial. JAMA 2018;epublished February 27th
2. Smith. Effect of intravenous β-2 agonist treatment on clinical outcomes in acute respiratory distress syndrome (BALTI-2): a multicentre, randomised controlled trial. Lancet epub ahead of print December 12 2011  (full text version)
3. NHLBI ARDSnet. Randomized, Placebo-controlled Clinical Trial of an Aerosolized ?2-Agonist for Treatment of Acute Lung Injury. Am J Resp Crit Care Med 2011;184:561-568
   
4. Perkins. The Beta-Agonist Lung Injury Trial (BALTI): A Randomized Placebo-controlled Clinical Trial.  Am J Respir Crit Care Med 2006;173:281–287

1. Villar. Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial. Lancet Respir Med 2020;8(3):267-276
2. Meduri. Methylprednisolone infusion in early severe ARDS: results of a randomized controlled trial. Chest 2007; 131:954-63.
3. Steinberg. Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. N Engl J Med 2006; 354:1671-84.  

1. Cornet. Recombinant human activated protein C in the treatment of acute respiratory distress syndrome: a randomized clinical trial. PLoS One 2014;14;9(3):e90983
2. Liu. Randomized Clinical Trial of Activated Protein C for the Treatment of Acute Lung Injury. Am J Respir Crit Care Med 2008;178(6):618-623

1. Willson. The Adult Calfactant in Acute Respiratory Distress Syndrome (CARDS) Trial. Chest 2015;epublished April 9th
2. Spragg. Recombinant Surfactant Protein C–based Surfactant for Patients with Severe Direct Lung Injury. American Journal of Respiratory and Critical Care Medicine 2011;183(8):1055 –1061
3. Kesecioglu. Exogenous Natural Surfactant for Treatment of Acute Lung Injury and the Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med 2009;180(10):989–994
4. Spragg. Effect of Recombinant Surfactant Protein C–Based Surfactant on the Acute Respiratory Distress Syndrome. N Engl J Med 2004;351(9):884–92
5. Spragg. Treatment of Acute Respiratory Distress Syndrome with Recombinant Surfactant Protein C Surfactant. Am J Respir Crit Care Med 2003;167(11):1562–6
6. Anzueto. Aerosolized surfactant in adults with sepsis-induced acute respiratory distress syndrome. Exosurf Acute Respiratory Distress Syndrome Sepsis Study Group. N Engl J Med 1996;334:1417–1421

1. Kor. Effect of Aspirin on Development of ARDS in At-Risk Patients Presenting to the Emergency DepartmentThe LIPS-A Randomized Clinical Trial (LIPS-A Trial). JAMA 2016;epublished May 15th