Major Trials
Circulatory
Sections
Fluid Therapy
Vasoactive Therapy
Blood Pressure
Mechanical Support
Goal-Directed Therapy
Intra-Arrest Drug Therapy
Intra-Arrest Airway management
Chest Compression
Post-Arrest Temperature Management
Misellaneous Post-Arrest Management
Fluid Therapy
Crystalloid vs Colloid
General Critical Care
Sepsis
- Perner. Hydroxyethyl Starch 130/0.4 versus Ringer's Acetate in Severe Sepsis (6S). N Eng J Med 2012; 367:124-134
- Guidet. Assessment of hemodynamic efficacy and safety of 6% hydroxyethylstarch 130/0.4 versus 0.9% NaCl fluid replacement in patients with severe sepsis: the CRYSTMAS study. Crit Care 2012;16:R94
- Brunkhorst. Intensive insulin therapy and pentastarch resuscitation in severe sepsis (VISEP). N Eng J Med 2008;358:125-139
Crystalloid vs Albumin
General Critical Care
Crystalloid vs Crystalloid
0.9% Saline vs Buffered Crystalloid
Intensive Care Unit
- Finfer. Balanced Multielectrolyte Solution versus Saline in Critically Ill Adults. N Engl J Med 2022;epublished January 18th
- 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
- Semler. Balanced Crystalloids versus Saline in Critically Ill Adults (SMART). N Engl J Med 2018;epublished February 27th
- Young. Effect of a Buffered Crystalloid Solution vs Saline on Acute Kidney Injury Among Patients in the Intensive Care Unit (SPLIT Trial). JAMA 2015;314(16):1701-1710
Emergency Department
Hypertonic Saline
- Asfar. Hyperoxia and hypertonic saline in patients with septic shock (HYPERS2S): a two-by-two factorial, multicentre, randomised, clinical trial. Lancet Respir Med 2017;5(3):180-190
- Roquilly. Effect of Continuous Infusion of Hypertonic Saline vs Standard Care on 6-Month Neurological Outcomes in Patients With Traumatic Brain InjuryThe COBI Randomized Clinical Trial. JAMA 2021;325(20):2056-2066
Volume of Fluid Resuscitation
No Fluid or Fluid Restriction
Sepsis
Trauma
Speed of Fluid Infusion
Rate of Resuscitation
General Critical Care
Vasoactive Therapy
Drug Comparisons
Individual Drugs
Noradrenaline
- De Backer. Comparison of dopamine and norepinephrine in the treatment of shock. N Engl 2010;362:779-89
- Myburgh. A comparison of epinephrine and norepinephrine in critically ill patients. Intensive Care Med 2008;34(12):2226-2234
- Annane. Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: A randomised trial. Lancet 2007; 370:676-684
- Seguin. Dopexamine and norepinephrine versus epinephrine on gastric perfusion in patients with septic shock: A randomized study. Crit Care 2006; 10:R32.
Adrenaline
- Ramaswamy. Double-Blind Randomized Clinical Trial Comparing Dopamine and Epinephrine in Pediatric Fluid-Refractory Hypotensive Septic Shock. Pediatr Crit Care Med 2016;epublished September 23rd
- Myburgh. A comparison of epinephrine and norepinephrine in critically ill patients. Intensive Care Med 2008;34(12):2226-2234 (abstract)
- Annane. Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: A randomised trial. Lancet 2007; 370:676-684
- Seguin. Dopexamine and norepinephrine versus epinephrine on gastric perfusion in patients with septic shock: A randomized study. Crit Care 2006; 10:R32.
Dopamine
- Ramaswamy. Double-Blind Randomized Clinical Trial Comparing Dopamine and Epinephrine in Pediatric Fluid-Refractory Hypotensive Septic Shock. Pediatr Crit Care Med 2016;epublished September 23rd
- De Backer. Comparison of dopamine and norepinephrine in the treatment of shock. N Engl 2010;362:779-89
- 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
Vasopressin
Levosimendan
- Follath. Efficacy and safety of intravenous levosimendan compared with dobutamine in severe low-output heart failure (the LIDO study): a randomised double-blind trial. Lancet 2002;360:196-202
- Nieminen. Randomized study on safety and effectiveness of levosimendan in patients with left ventricular failure after an acute myocardial infarction (RUSSLAN). European Heart Journal 2002;23:1422-32
Angiotensin II
Blood Pressure Targets
General
- 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
- Lamontagne. Higher versus lower blood pressure targets for vasopressor therapy in shock: a multicentre pilot randomized controlled trial. (OVATION). Intensive Care Med 2016;42:542-550
Sepsis
- Endo. Efficacy of targeting high mean arterial pressure for older patients with septic shock (OPTPRESS): a multicentre, pragmatic, open-label, randomised controlled trial. Intensive Care Med 2025;epublished May 13th
- Asfar. High versus low blood-pressure target in patients with septic shock. (SEPSISPAM). N Engl J Med 2014;370(17):1583-1593
Mechanical Support
Intra-Aortic Balloon Pump
- Morici. Early Intra-Aortic Balloon Support for Heart Failure-Related Cardiogenic Shock: A Randomized Clinical Trial (Altshock-2). JACC 2025;epublished March 30th
- Ouweneel. Percutaneous mechanical circulatory support versus intra-aortic balloon pump in cardiogenic shock after acute myocardial infarction. J Am Coll Cardiol 2017;69:3:278-287
- Thiele. Intraaortic Balloon Support for Myocardial Infarction with Cardiogenic Shock (IABP-SHOCK II Trial). NEJM 2012;367(14):1287-1296
- Burkhoff. A randomized multicenter clinical study to evaluate the safety and efficacy of the TandemHeart percutaneous ventricular assist device versus conventional therapy with intraaortic balloon pumping for treatment of cardiogenic shock. Am Heart J 2006;152:3:469.e1-469.e8
ECMO
Left Ventricular Assist Device
Total Artificial Heart
Mechanical Chest Compression Devices
- Perkins. Mechanical versus manual chest compression for out-of-hospital cardiac arrest (PARAMEDIC): a pragmatic, cluster randomised controlled trial. Lancet 2014;epublished November 16th
- Wik. Manual vs. integrated automatic load-distributing band CPR with equal survival after out of hospital cardiac arrest. The randomized CIRC trial. Resuscitation 2014;epublished March 15th
- Rubertsson. Mechanical Chest Compressions and Simultaneous Defibrillation vs Conventional Cardiopulmonary Resuscitation in Out-of-Hospital Cardiac Arrest. The LINC Randomized Trial. JAMA 2013;311(1):53-61
Goal-Directed Therapy
Pulmonary Artery Catheter
Intensive Care Unit
- 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
- Rhodes. A randomised, controlled trial of the pulmonary artery catheter in critically ill patients. Intensive Care Med 2002;28:256–264
Acute Respiratory Distress Syndrome
- The National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network. Pulmonary-Artery versus Central Venous Catheter to Guide Treatment of Acute Lung Injury. N Engl J Med 2006;354:2213-24
- Richard. Early use of the pulmonary artery catheter and outcomes in patients with shock and acute respiratory distress syndrome: A randomized controlled trial. JAMA 2003; 290: 2713–2720
SvO2
Intensive Care Unit
Sepsis
- 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
- Rivers. Early goal directed therapy in the treatment of severe sepsis and septic shock. N Eng J Med 2001;345:1368-77
Miscellaneous Goal Directed Approaches
Lactate
- Hernández. Effect of a Resuscitation Strategy Targeting Peripheral Perfusion Status vs Serum Lactate Levels on 28-Day Mortality Among Patients With Septic Shock: The ANDROMEDA-SHOCK Randomized Clinical Trial. JAMA 2019;321(7):654-664
- Jones. Lactate Clearance vs Central Venous Oxygen Saturation as Goals of Early Sepsis Therapy. JAMA. 2010;303(8):739-746.
- Jansen. Early Lactate-Guided Therapy in ICU Patients: A Multicenter, Open-Label, Randomized, Controlled Trial. Am. J. Respir. Crit. Care Med. 2010;182: 752-761
Percutaneous Coronary Intervention
Timing of Angiography
Cardiac Arrest
Intra-Arrest Management
Intra-Arrest Drug Therapy
Combination Therapy
- Andersen. Effect of Vasopressin and Methylprednisolone vs Placebo on Return of Spontaneous Circulation in Patients With In-Hospital Cardiac Arrest. A Randomized Clinical Trial. JAMA 2021;epublished September 29th
- Mentzelopoulos. Vasopressin, Steroids, and Epinephrine and Neurologically Favorable Survival After In-Hospital Cardiac Arrest: A Randomized Clinical Trial. JAMA 2013;310(3):270
- Mentzelopoulos. Vasopressin, epinephrine, and corticosteroids for in-hospital cardiac arrest. Arch Intern Med. 2009;169:15–24
- Olasveengen. Intravenous Drug Administration During Out-of-Hospital Cardiac Arrest: A Randomized Trial. JAMA 2009;302(20):2222-2229
Adrenaline
- Perkins. A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest (PARAMEDIC2). N Engl J Med 2018;epublished July 18th
- Jacobs. Effect of adrenaline on survival in out-of-hospital cardiac arrest: A randomised double-blind placebo-controlled trial (PACA Trial). Resuscitation 2011;82(9):1138-43
- Gueugniaud. A comparison of repeated high doses and repeated standard doses of epinephrine for cardiac arrest outside the hospital. European epinephrine study group. N Engl J Med 1998;339(22):1595–601
Vasopressin vs Adrenaline
- Ong. A randomised, double-blind, multi-Centre trial comparing vasopressin and adrenaline in patients with cardiac arrest presenting to or in the emergency department. Resuscitation 2012;83:953–60
- Wenzel. A comparison of vasopressin and epinephrine for out-of-hospital cardiopulmonary resuscitation. N Engl J Med 2004;350:105–13
- Lindner. Randomized comparison of epinephrine and vasopressin in patients with out-of-hospital ventricular fibrillation. Lancet 1997;349:535–7
Amidarone vs Lidocaine
- Kudenchuk. Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest. N Engl J Med 2016;epublished April 4th
- Dorian. Amiodarone as compared with lidocaine for shock- resistant ventricular fibrillation. N Engl J Med 2002;346(12):884–90
- Somberg. Intravenous lidocaine versus intravenous amiodarone (in a new aqueous formulation) for incessant ventricular tachycardia. Am J Cardiol. 2002;90(8):853–9
Magnesium
- Hassan. A randomised trial to investigate the efficacy of magnesium sulphate for refractory ventricular fibrillation. Emerg Med J. 2002;19:57–62
- Allegra. Magnesium sulfate in the treatment of refractory ventricular fibrillation in the prehospital setting. Resuscitation. 2001;49:245–9
- Thel. Randomised trial of magnesium in in-hospital cardiac arrest. Duke internal medicine housestaff. Lancet 1997;350:1272–6
- Fatovich. Magnesium in cardiac arrest (the magic trial). Resuscitation. 1997;35:237–41
- Miller. Pilot study of intravenous magnesium sulfate in refractory cardiac arrest: safety data and recommendations for future studies. Resuscitation. 1995;30:3–14
Buffer Therapy
Bretylium
- Olson. A randomized comparison study of bretylium tosylate and lidocaine in resuscitation of patients from out-of-hospital ventricular fibrillation in a paramedic system. Ann Emerg Med 1984;13:807–10
- Haynes. Comparison of bretylium tosylate and lidocaine in management of out of hospital ventricular fibrillation: a randomized clinical trial. Am J Cardiol. 1981;48(2):353–6
- Nowak. Bretylium tosylate as initial treatment for cardiopulmonary arrest: randomized comparison with placebo. Ann Emerg Med. 1981;10(8):404–7
Intra-Arrest Airway Management
Cricoid Pressure
SGA vs ETT
- Wang. Effect of a Strategy of Initial Laryngeal Tube Insertion vs Endotracheal Intubation on 72-Hour Survival in Adults With Out-of-Hospital Cardiac Arrest. A Randomized Clinical Trial. JAMA 2018;320(8):769-778
- 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
Chest Compression
Devices
- Perkins. Mechanical versus manual chest compression for out-of-hospital cardiac arrest (PARAMEDIC): a pragmatic, cluster randomised controlled trial. Lancet 2014;epublished November 16th
- Wik. Manual vs. integrated automatic load-distributing band CPR with equal survival after out of hospital cardiac arrest. The randomized CIRC trial. Resuscitation 2014;epublished March 15th
- Rubertsson. Mechanical Chest Compressions and Simultaneous Defibrillation vs Conventional Cardiopulmonary Resuscitation in Out-of-Hospital Cardiac Arrest. The LINC Randomized Trial. JAMA 2013;311(1):53-61
Compression Rates
Post Arrest Management
Temperature Management
Temperature Comparisons
- Le May. Effect of Moderate vs Mild Therapeutic Hypothermia on Mortality and Neurologic Outcomes in Comatose Survivors of Out-of-Hospital Cardiac Arrest: The CAPITAL CHILL Randomized Clinical Trial. JAMA 2021;326(15):1494-1503
- Dankiewicz. Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest. N Engl J Med 2021;384:2283-2294
- Lascarrou. Targeted Temperature Management for Cardiac Arrest with Nonshockable Rhythm. N Engl J Med N Engl J Med 2019;381:2327-2337
- Nielsen. Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest (TTM study). N Engl J Med 2013;369:2197-2206
- Kim. Effect of Prehospital Induction of Mild Hypothermia on Survival and Neurological Status Among Adults With Cardiac Arrest: A Randomized Clinical Trial. JAMA 2014;311(1):45-52
- Bernard. Treatment of Comatose Survivors of Out-of-Hospital Cardiac Arrest with Induced Hypothermia. N Engl J Med 2002; 346:557-563
- The Hypothermia after Cardiac Arrest Study Group. Mild Therapeutic Hypothermia to Improve the Neurologic Outcome after Cardiac Arrest. N Engl J Med 2002; 346:549-556
Intra-Arrest Cooling
- Nordberg. Effect of trans-nasal evaporative intra-arrest cooling on functional neurologic outcome in out-of-hospital cardiac arrest: the PRINCESS randomized clinical trial. JAMA 2019;321(17):1677–85
- Bernard. Induction of Therapeutic Hypothermia During Out-of-Hospital Cardiac Arrest Using a Rapid Infusion of Cold Saline: The RINSE Trial (Rapid Infusion of Cold Normal Saline). Circulation 2016;134(11):797-805
Cooling Method
Duration of Cooling
Paediatrics
Miscellaneous Post Arrest Management
Blood Pressure
Oxygenation
Percutaneous Coronary Intervention
Coronary Angiography Post Cardiac Arrest
Cardiogenic Shock
Last updated March 31st, 2025