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Chesnut. A Trial of Intracranial-Pressure Monitoring in Traumatic Brain Injury. New Engl J Med 2012;367:2471-2481
Hutchinson. Trial of Decompressive Craniectomy for Traumatic Intracranial Hypertension (RESCUEicp). N Engl J Med 2016;375:1119-1130
Critique
Turgeon. Liberal or Restrictive Transfusion Strategy in Patients with Traumatic Brain Injury. N Eng J Med 2024;391:722-735
Andrews. Hypothermia for Intracranial Hypertension after Traumatic Brain Injury (Eurotherm3235 Trial). N Engl J Med 2015;epublished October 7th
CRASH trial collaborators. Effect of intravenous corticosteroids on death within 14 days in 10 008 adults with clinically significant head injury (MRC CRASH trial): randomised placebo-controlled trial. Lancet 2004;364(9442):1321-1328
Molyneux. International Subarachnoid Aneurysm Trial (ISAT) of neurosurgical clipping versus endovascular coiling in 2143 patients with ruptured intracranial aneurysms: a randomised trial. Lancet 2002;360(9342):1267-74
Kress. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med 2000;342:1471-7
Legriel. Hypothermia for Neuroprotection in Convulsive Status Epilepticus (HYBERNATUS Study). N Engl J Med 2016;375:2457-2467
Finfer. A comparison of albumin and saline for fluid resuscitation in the intensive care unit (SAFE). N Engl J Med 2004;350(22):2247-56
Myburgh. Hydroxyethyl Starch or Saline for Fluid Resuscitation in Intensive Care (CHEST). NEJM 2012;367:1901-1911
Perner. Hydroxyethyl Starch 130/0.4 versus Ringer's Acetate in Severe Sepsis (6S). N Eng J Med 2012; 367:124-134
Zampieri. Effect of Intravenous Fluid Treatment With a Balanced Solution vs 0.9% Saline Solution on Mortality in Critically Ill PatientsThe BaSICS Randomized Clinical Trial. JAMA 2021;epublished August 10th
McIntyre. A Crossover Trial of Hospital-Wide Lactated Ringer’s Solution versus Normal Saline. NEJM 2025;epublished June 12th
Meyhoff. Restriction of Intravenous Fluid in ICU Patients with Septic Shock. N Engl J Med 2022;386:2459-2470
Maitland. Mortality after Fluid Bolus in African Children with Severe Infection (FEAST Trial). N Engl J Med 2011
De Backer. Comparison of dopamine and norepinephrine in the treatment of shock. N Engl 2010;362:779-89
Russell. Vasopressin versus norepinephrine infusion in patients with septic shock (VASST). NEJM 2008;358:877-87
Lamontagne. Effect of Reduced Exposure to Vasopressors on 90-Day Mortality in Older Critically Ill Patients With Vasodilatory Hypotension. A Randomized Clinical Trial. (65). JAMA 2020;323(10):938-949
Thiele. Intraaortic Balloon Support for Myocardial Infarction with Cardiogenic Shock (IABP-SHOCK II Trial). NEJM 2012;367(14):1287-1296
Møller. DanGer Shock Investigators. Microaxial flow pump or standard care in infarct-related cardiogenic shock. N Engl J Med. 2024;390(15):1382-1393
Thiele. Extracorporeal life support in infarct-related cardiogenic shock. N Engl J Med 2023;389(14):1286-1297
Harvey. Assessment of the clinical effectiveness of pulmonary artery catheters in management of patients in intensive care (PAC-Man): a randomised controlled trial. Lancet 2006;366:472 - 477
Mouncey. Trial of Early, Goal-Directed Resuscitation for Septic Shock. (ProMISe Trial). N Engl J Med 2015;epublished March 17th
The ARISE Investigators. Goal-Directed Resuscitation for Patients with Early Septic Shock. New Engl J Med 2014;epublished October 1st
The ProCESS Investigators. A Randomized Trial of Protocol-Based Care for Early Septic Shock (ProCESS study). New Engl J Med 2014;epublished March 18th
Hayes. Elevation of systemic oxygen delivery in the treatment of critically ill patients. N Engl J Med 1994, 330:1717-1722
Gattinoni. A trial of goal-oriented hemodynamic therapy in critically ill patients. SvO2 Collaborative Group. N Engl J Med 1995;333:1025-1032
Thiele. PCI Strategies in Patients with Acute Myocardial Infarction and Cardiogenic Shock. N Engl J Med 2017;377:2419-2432
The National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Clinical Trials Network. Early Restrictive or Liberal Fluid Management for Sepsis-Induced Hypotension (CLOVERS). N Engl J Med 2023;388:499-510
Caironi. Albumin Replacement in Patients with Severe Sepsis or Septic Shock (ALBIOS study). New Engl J Med 2014;epublished March 18th
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
Guérin. Prone Positioning in Severe Acute Respiratory Distress Syndrome (PROSEVA). New Engl J Med 2013;368:2159-2168
Martin. Conservative Oxygen Therapy in Mechanically Ventilated Critically Ill Adult PatientsThe UK-ROX Randomized Clinical Trial. JAMA 2025;epublished June 12th
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 ARDS. A Randomized Clinical Trial. JAMA 2018;epublished October 24th
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
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
Papazian. Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med 2010;363:1107-1116
Wiedemann. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med. 2006; 354:2564-75
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
Combes. Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome (EOLIA Trial). N Engl J Med 2018;378:1965-75
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
Ferguson. High-Frequency Oscillation in Early Acute Respiratory Distress Syndrome (OSCILLATE). New Engl J Med 2013;epublished January 22rd
Young. High-Frequency Oscillation for Acute Respiratory Distress Syndrome (OSCAR). New Engl J Med 2013;epublished January 22nd
Frat. High-Flow Oxygen through Nasal Cannula in Acute Hypoxemic Respiratory Failure (FLORALI study). N Eng J Med 2015;epublished May 17th
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
Jabaudon. Inhaled Sedation in Acute Respiratory Distress SyndromeThe SESAR Randomized Clinical Trial. JAMA 2025;epublished March 18th
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;351:327-336
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
The BALANCE Investigators. Antibiotic Treatment for 7 versus 14 Days in Patients with Bloodstream Infections. N Engl J Med 2024;epublished November 20th
Dark. Biomarker-Guided Antibiotic Duration for Hospitalized Patients With Suspected Sepsis. The ADAPT-Sepsis Randomized Clinical Trial. JAMA 2024;epublished December 9th
Sawyer. Trial of Short-Course Antimicrobial Therapy for Intraabdominal Infection (STOP-IT trial). N Engl J Med 2015; 372:1996-2005
Venkatesh. Adjunctive Glucocorticoid Therapy in Patients with Septic Shock (ADRENAL). N Engl J Med 2018;2018;378:797-808
Annane. Hydrocortisone plus Fludrocortisone for Adults with Septic Shock (APROCCHSS). N Engl J Med 2018;378:809-818
Annane. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 2002;288:862-871
Ranieri. Drotrecogin Alfa (Activated) in Adults with Septic Shock (PROWESS-SHOCK Study). N Engl J Med 2012;366:2055-206
Lamontagne. Intravenous vitamin C in adults with sepsis in the intensive care unit. N Engl J Med 2022;386:2387–2398
Dulhunty. Continuous vs Intermittent β-Lactam Antibiotic Infusions in Critically Ill Patients With Sepsis. The BLING III Randomized Clinical Trial. JAMA 2024;332;(8):629-637
Birenbaum. Cricoid Pressure Compared With a Sham Procedure in Rapid Sequence Induction of Anesthesia. JAMA Surg 2018;epublished October 17th
Benger. Effect of a Strategy of a Supraglottic Airway Device vs Tracheal Intubation During Out-of-Hospital Cardiac Arrest on Functional Outcome. The AIRWAYS-2 Randomized Clinical Trial. JAMA 2018;320(8):779-791
Driver. Effect of Use of a Bougie vs Endotracheal Tube With Stylet on Successful Intubation on the First Attempt Among Critically Ill Patients Undergoing Tracheal Intubation. A Randomized Clinical Trial. JAMA 2021;epublished December 8th
(CCR Livestream Presentation)
Gibbs. Noninvasive Ventilation for Preoxygenation during Emergency Intubation. N Eng J Med 2024;epublished June 13th
Casey. Bag-Mask Ventilation during Tracheal Intubation of Critically Ill Adults. N Engl J Med 2019; 380:811-821
Russell. Effect of Fluid Bolus Administration on Cardiovascular Collapse Among Critically Ill Patients Undergoing Tracheal Intubation (PREPARE II). A Randomized Clinical Trial. JAMA 2022;328(3):270-279
Prekker. Video versus Direct Laryngoscopy for Tracheal Intubation of Critically Ill Adults (DEVICE). N Engl J Med 2023;389:418-429
Young. Effect of Early vs Late Tracheostomy Placement on Survival in Patients Receiving Mechanical Ventilation: The TracMan Randomized Trial. JAMA 2013;309(20):2121
Perkins. A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest (PARAMEDIC2). N Engl J Med 2018;epublished July 18th
Kudenchuk. Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest. N Engl J Med 2016;epublished April 4th
Perkins. Mechanical versus manual chest compression for out-of-hospital cardiac arrest (PARAMEDIC): a pragmatic, cluster randomised controlled trial. Lancet 2014;epublished November 16th
Lemkes. Coronary Angiography after Cardiac Arrest without ST-Segment Elevation (COACT). N Engl J Med 2019;epublished March 18th
Vallentin. Effect of Intravenous or Intraosseous Calcium vs Saline on Return of Spontaneous Circulation in Adults With Out-of-Hospital Cardiac Arrest. A Randomized Clinical Trial. JAMA 2021;326(22):2268-2276
Nielsen. Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest (TTM study). N Engl J Med 2013;369:2197-2206
Dankiewicz. Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest. N Engl J Med 2021;384:2283-2294
de-Madaria. Aggressive or Moderate Fluid Resuscitation in Acute Pancreatitis. N Engl J Med 2022;387:989-1000
Boxhoorn. Immediate versus Postponed Intervention for Infected Necrotizing Pancreatitis. N Engl J Med 2021;385:1372-1381
Villanueva. Transfusion Strategies for Acute Upper Gastrointestinal Bleeding. N Engl J Med 2013;368:11-21
Keays. Intravenous acetylcysteine in paracetamol induced fulminant hepatic failure: a prospective controlled trial. BMJ 1991;303:1026-1029
The HALT-IT Trial Collaborators. Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial. Lancet 2020;395(10241):1927-1936
Cook. Stress Ulcer Prophylaxis during Invasive Mechanical Ventilation. N Engl J Med 2024;391:9-20
The PEPTIC Investigators. Effect of Stress Ulcer Prophylaxis With Proton Pump Inhibitors vs Histamine-2 Receptor Blockers on In-Hospital Mortality Among ICU Patients Receiving Invasive Mechanical VentilationThe PEPTIC Randomized Clinical Trial. JAMA 2020;2020;323(7):616-626
Maitland. Intravenous Rehydration for Severe Acute Malnutrition with Gastroenteritis. NEJM 2025;epublished June 13th
China. A Randomized Trial of Albumin Infusions in Hospitalized Patients with Cirrhosis. N Engl J Med 2021;384:808-817
Sort. Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis. N Engl J Med 1999;341:403–409
Wong. Terlipressin plus Albumin for the Treatment of Type 1 Hepatorenal Syndrome. N Engl J Med 2021; 384:818-828
Hebert. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. N Engl J Med 1999;340:409-17
English. Liberal or Restrictive Transfusion Strategy in Aneurysmal Subarachnoid Hemorrhage. N Engl J Med 2024;epublished December 9th
Turgeon.Liberal or Restrictive Transfusion Strategy in Patients with Traumatic Brain Injury. N Eng J Med 2024;391:722-735
Holcomb. Transfusion of Plasma, Platelets, and Red Blood Cells in a 1:1:1 vs a 1:1:2 Ratio and Mortality in Patients With Severe Trauma: The PROPPR Randomized Clinical Trial. JAMA 2015;313(5):471
Sperry. Prehospital Plasma during Air Medical Transport in Trauma Patients at Risk for Hemorrhagic Shock. N Engl J Med 2018; 379:315-326
Shakur. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet 2010;376(9734):23–32
The CRASH-3 trial collaborators. Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): a randomised, placebo-controlled trial. Lancet 2019;394(10210):1713-1723
The PATCH-Trauma Investigators and the ANZICS Clinical Trials Group. Prehospital Tranexamic Acid for Severe Trauma. N Engl J Med 2023;epublished June 14th
The PROTECT Investigators. Dalteparin versus Unfractionated Heparin in Critically Ill Patients. N Engl J Med 2011;364:1305-14
Arabi. Adjunctive Intermittent Pneumatic Compression for Venous Thromboprophylaxis. N Engl J Med 2019;epublished February 18th
Ducrocq. Effect of a Restrictive vs Liberal Blood Transfusion Strategy on Major Cardiovascular Events Among Patients With Acute Myocardial Infarction and Anemia. The REALITY Randomized Clinical Trial. JAMA 2021;325(6):552-560
Villanueva. Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med 2013;368(1):11-21
Corwin. Efficacy and Safety of Epoetin Alfa in Critically Ill Patients. N Engl J Med 2007; 357:965-976
NICE-SUGAR Study Investigators. Intensive versus Conventional Glucose Control in Critically Ill Patients. N Engl J Med 2009;360:1283-97.
The National Heart, Lung, and Blood Institute PETAL Clinical Trials Network. Early High-Dose Vitamin D3 for Critically Ill, Vitamin D–Deficient Patients (VIOLET). N Engl J Med 2019; 381:2529-2540
Sevransky. Effect of Vitamin C, Thiamine, and Hydrocortisone on Ventilator- and Vasopressor-Free Days in Patients With Sepsis. The VICTAS Randomized Clinical Trial. JAMA 2021;325(8):742-750
Vinsonneau. Continuous venovenous haemodiafiltration versus intermittent haemodialysis for acute renal failure in patients with multiple-organ dysfunction syndrome: A multicentre randomised trial. Lancet 2006; 368:379-385
The STARRT-AKI Investigators. Timing of Initiation of Renal-Replacement Therapy in Acute Kidney Injury. N Engl J Med 2020;383:240-251
RENAL Replacement Therapy Study Investigators. Intensity of continuous renal-replacement therapy in critically ill patients (RENAL study). N Engl J Med 2009;361(17):1627-38
Zarbock. Effect of Regional Citrate Anticoagulation vs Systemic Heparin Anticoagulation During Continuous Kidney Replacement Therapy on Dialysis Filter Life Span and Mortality Among Critically Ill Patients With Acute Kidney Injury. A Randomized Clinical Trial. JAMA 2020;324(16):1629-1639
Landoni. A Randomized Trial of Intravenous Amino Acids for Kidney Protection. N Eng J Med 2024;epublished June 12th
Jaber. Sodium bicarbonate therapy for patients with severe metabolic acidaemia in the intensive care unit (BICAR-ICU): a multicentre, open-label, randomised controlled, phase 3 trial. Lancet 2018;392(10141):31-40
Bellomo. Low-dose dopamine in patients with early renal dysfunction: a placebo-controlled randomised trial. Australian and New Zealand Intensive Care Society (ANZICS) Clinical Trials Group. Lancet 2000; 356: 2139-43.
Bouzat. Efficacy and Safety of Early Administration of 4-Factor Prothrombin Complex Concentrate in Patients With Trauma at Risk of Massive Transfusion. The PROCOAG Randomized Clinical Trial. JAMA 2023;epublished March 21st
Davenport. Early and Empirical High-Dose Cryoprecipitate for Hemorrhage After Traumatic Injury. The CRYOSTAT-2 Randomized Clinical Trial. JAMA 2023;epublished October 12th
Bickell. Immediate versus delayed fluid resuscitaion for hypotensive patients with penetrating torso injuries. N Engl J Med 1994;331:1105-1109
The PATCH-Trauma Investigators and the ANZICS Clinical Trials Group. Prehospital Tranexamic Acid for Severe Trauma. N Engl J Med 2023;389:127-136
CRASH-2 trial collaborators. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet 2010;376:23-32
Arabi. Permissive Underfeeding or Standard Enteral Feeding in Critically Ill Adults (PermiT). N Engl J Med 2015;372:2398-2408
Doig. Early Parenteral Nutrition in Critically Ill Patients With Short-term Relative Contraindications to Early Enteral Nutrition: A Randomized Controlled Trial. JAMA 2013;309(20):2130-2138
Casaer. Early versus Late Parenteral Nutrition in Critically Ill Adults (EPaNIC). N Eng J Med 2011;365:506-517
Fivez. Early versus Late Parenteral Nutrition in Critically Ill Children (PEPaNIC). N Engl J Med 2016;374:1111-1122
Harvey. Trial of the Route of Early Nutritional Support in Critically Ill Adults (CALORIES). New Engl J Med 2014;371:1673-1684
Summers. Augmented Enteral Protein During Critical Illness. The TARGET Protein Randomized Clinical Trial. JAMA 2025;epublished June 11th
Heyland. A randomized trial of glutamine and antioxidants in critically ill patients (REDOXS). N Engl J Med 2013;368:1489-1497
Pereira. Effect of Tele-ICU on Clinical Outcomes of Critically Ill Patients. The TELESCOPE Randomized Clinical Trial. JAMA 2024;epublished October 9th
BRICNet. Effect of a Quality Improvement Intervention With Daily Round Checklists, Goal Setting, and Clinician Prompting on Mortality of Critically Ill Patients. A Randomized Clinical Trial (CHECKLIST-ICU). JAMA 2016;315(14):1480-1490
The TEAM Study Investigators and the ANZICS Clinical Trials Group. Early Active Mobilization during Mechanical Ventilation in the ICU. N Engl J Med 2022; 387:1747-1758
Last updated August 11th, 2025
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