Hot Trials 2021

Dexamethasone

1. The COVID STEROID 2 Trial Group. Effect of 12 mg vs 6 mg of Dexamethasone on the Number of Days Alive Without Life Support in Adults With COVID-19 and Severe HypoxemiaThe COVID STEROID 2 Randomized Trial. JAMA 2021;epublished October 21st
2. Granholm. Dexamethasone 12 mg versus 6 mg for patients with COVID-19 and severe hypoxaemia: a pre-planned, secondary Bayesian analysis of the COVID STEROID 2 trial. Intensive Care Med 2021;epublished November 10th
3. The RECOVERY Collaborative Group. Dexamethasone in Hospitalized Patients with Covid-19.N Engl J Med 2021;384:693-704

Il-6 Antagonists

1. Sancho-López. Efficacy and Safety of Sarilumab in patients with COVID19 Pneumonia: A Randomized, Phase III Clinical Trial (SARTRE Study). Infect Dis Ther 2021;epublished October 17th
2. Rosas. Tocilizumab and remdesivir in hospitalized patients with severe COVID-19 pneumonia: a randomized clinical trial. Intensive Care Med 2021;epublished October 5th
3. The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group. Association Between Administration of IL-6 Antagonists and Mortality Among Patients Hospitalized for COVID-19A Meta-analysis. JAMA 2021;epublished July 6th
4. RECOVERY Collaborative Group. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet 2021;397(10285):1637-1645
5. Cremer. Mavrilimumab in patients with severe COVID-19 pneumonia and systemic hyperinflammation (MASH-COVID): an investigator initiated, multicentre, double-blind, randomised, placebo-controlled trial. Lancet Rheumatol 2021;epublished March 17th
6. The REMAP-CAP Investigators. Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19. N Engl J Med 2021;epublished February 25th
7. Rosas. Tocilizumab in Hospitalized Patients with Severe Covid-19 Pneumonia. N Engl J Med 2021;epublished February 25th
8. Salama. Tocilizumab in Patients Hospitalized with Covid-19 Pneumonia. N Engl J Med 2021;384:20-30
9. Lescure. Sarilumab in patients admitted to hospital with severe or critical COVID-19: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Respir Med 2021;epublished March 4th
10. Soin. Tocilizumab plus standard care versus standard care in patients in India with moderate to severe COVID-19-associated cytokine release syndrome (COVINTOC): an open-label, multicentre, randomised, controlled, phase 3 trial. Lancet Respir Med 2021;epublished March 4th

Methylprednisolone

1. Edalatifard. Intravenous methylprednisolone pulse as a treatment for hospitalised severe COVID-19 patients: results from a randomised controlled clinical trial. Eur Respir J 2020;56:2002808

Anticoagulation

1. Sholzberg. Effectiveness of therapeutic heparin versus prophylactic heparin on death, mechanical ventilation, or intensive care unit admission in moderately ill patients with covid-19 admitted to hospital: RAPID randomised clinical trial. BMJ 2021;375:n2400
2. Spyropoulos. Efficacy and Safety of Therapeutic-Dose Heparin vs Standard Prophylactic or Intermediate-Dose Heparins for Thromboprophylaxis in High-risk Hospitalized Patients With COVID-19The HEP-COVID Randomized Clinical Trial. JAMA Intern Med 2021;epublished October 7th
3. The REMAP-CAP, ACTIV-4a, and ATTACC Investigators. Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19. N Engl J Med 2021;epublished August 4th
4. The REMAP-CAP, ACTIV-4a, and ATTACC Investigators. Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19. N Engl J Med 2021;epublished August 4th
5. Lopes. Therapeutic versus prophylactic anticoagulation for patients admitted to hospital with COVID-19 and elevated D-dimer concentration (ACTION): an open-label, multicentre, randomised, controlled trial. Lancet 2021;epublished June 4th
6. INSPIRATION Investigators. Effect of Intermediate-Dose vs Standard-Dose Prophylactic Anticoagulation on Thrombotic Events, Extracorporeal Membrane Oxygenation Treatment, or Mortality Among Patients With COVID-19 Admitted to the Intensive Care Unit. The INSPIRATION Randomized Clinical Trial. JAMA 2021;epublished March 18th

Azithromycin

1. RECOVERY Collaborative Group. Azithromycin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet 2021;epublished February 2nd

Convalescent Plasma

1. Writing Committee for the REMAP-CAP Investigators. Effect of Convalescent Plasma on Organ Support–Free Days in Critically Ill Patients With COVID-19A Randomized Clinical Trial. JAMA 2021;epublished October 4th
2. Bégin. Convalescent plasma for hospitalized patients with COVID-19: an open-label, randomized controlled trial. Nat Med 2021;epublished September 9th
3. RECOVERY Collaborative Group. Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial. Lancet 2021;epublished May 14th
4. Libster. Early High-Titer Plasma Therapy to Prevent Severe Covid-19 in Older Adults. N Engl J Med 2021;epublished January 6th

Respiratory Support

1. Ospina-Tascón. Effect of High-Flow Oxygen Therapy vs Conventional Oxygen Therapy on Invasive Mechanical Ventilation and Clinical Recovery in Patients With Severe COVID-19A Randomized Clinical Trial. JAMA 2021;326(21):2161-2171
2. Ibarra-Estrada. Use of Airway Pressure Release Ventilation in Patients With Acute Respiratory Failure Due to Coronavirus Disease 2019: Results of a Single-Center Randomized Controlled Trial. Crit Care Med 2021;epublished September 29th
3. Grieco. Effect of Helmet Noninvasive Ventilation vs High-Flow Nasal Oxygen on Days Free of Respiratory Support in Patients With COVID-19 and Moderate to Severe Hypoxemic Respiratory Failure. The HENIVOT Randomized Clinical Trial. JAMA 2021;epublished March 25th

JAK Inhibitors

1. Ely. Baricitinib plus Standard of Care for Hospitalised Adults with COVID-19 on Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation: Results of a Randomised, Placebo-Controlled Trial. MedRxiv 2021;epublished October 12th
2. Marconi. Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): a randomised, double-blind, parallel-group, placebo-controlled phase 3 trial. Lancet Respir Med 2021;epublished September 1st
3. Guimarães. Tofacitinib in Patients Hospitalized with Covid-19 Pneumonia. N Engl J Med 2021;385:406-415
4. Aman. Imatinib in patients with severe COVID-19: a randomised, double-blind, placebo-controlled, clinical trial. Lancet Respir Med 2021;epublished June 17th
5. Guimarães. Tofacitinib in Patients Hospitalized with Covid-19 Pneumonia. N Engl J Med 2021;epublished June 16th

Anti–Interleukin-1β Antibody

• Caricchio. Effect of Canakinumab vs Placebo on Survival Without Invasive Mechanical Ventilation in Patients Hospitalized With Severe COVID-19. A Randomized Clinical Trial. JAMA 2021;326(3):230-239

Interferon

• Kalil. Efficacy of interferon beta-1a plus remdesivir compared with remdesivir alone in hospitalised adults with COVID-19: a double-bind, randomised, placebo-controlled, phase 3 trial. Lancet Respir Med 2021;epublished October 18th

Antivirals

1. Arabi. Lopinavir-ritonavir and hydroxychloroquine for critically ill patients with COVID-19: REMAP-CAP randomized controlled trial. Intensive Care Med 2021;epublished July 12th

Monoclonal Antibodies

1. Temesgen. Lenzilumab in hospitalised patients with COVID-19 pneumonia (LIVE-AIR): a phase 3, randomised, placebo-controlled trial. Lancet Respir Med 2021;epublished December 1st
2. Weinreich. REGEN-COV Antibody Combination and Outcomes in Outpatients with Covid-19. N Engl J Med 2021;epublished September 29th
3. Cohen. BLAZE-2 Investigators. Effect of bamlanivimab vs placebo on incidence of COVID-19 among residents and staff of skilled nursing and assisted living facilities: a randomized clinical trial. JAMA 2021;epublished June 3rd

Immunoglobulins

1. Mazeraud. Intravenous immunoglobulins in patients with COVID-19-associated moderate-to-severe acute respiratory distress syndrome (ICAR): multicentre, double-blind, placebo-controlled, phase 3 trial. Lancet respir Med 2021;epublished November 11th

Antifungal Therapy

1. Vanderbeke. Posaconazole for prevention of invasive pulmonary aspergillosis in critically ill influenza patients (POSA-FLU): a randomised, open-label, proof-of-concept trial. Intensive Care Med 2021;epublished May 29th

Miscellaneous

1. Supady. Cytokine adsorption in patients with severe COVID-19 pneumonia requiring extracorporeal membrane oxygenation (CYCOV): a single centre, open-label, randomised, controlled trial. Lancet Respir Med 2021;epublished May 14th

Observational Studies

Multisystem Inflammatory Syndrome

1. Son. Multisystem Inflammatory Syndrome in Children — Initial Therapy and Outcomes. N Engl J Med 2021;385:23-34
2. McArdle. Treatment of Multisystem Inflammatory Syndrome in Children. N Engl J Med 2021;385:11-22

Vaccine Induced Thrombotic Thrombocytopaenia

1. Bourguignon. Adjunct Immune Globulin for Vaccine-Induced Thrombotic Thrombocytopenia. N Engl J Med 2021;epublished June 9th
2. Scully. Pathologic Antibodies to Platelet Factor 4 after ChAdOx1 nCoV-19 Vaccination. N Engl J Med 2021;384:2202-2211
3. Greinacher. Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination. N Engl J Med 2021;epublished April 9th
4. Schultz. Thrombosis and Thrombocytopenia after ChAdOx1 nCoV-19 Vaccination. N Engl J Med 2021;epublished April 9th

1. Lapergue. Effect of Thrombectomy With Combined Contact Aspiration and Stent Retriever vs Stent Retriever Alone on Revascularization in Patients With Acute Ischemic Stroke and Large Vessel Occlusion. The ASTER2 Randomized Clinical Trial. JAMA 2021;326(12):1158-1169
2. Hergenroeder. Hypothermia for Patients Requiring Evacuation of Subdural Hematoma: A Multicenter Randomized Clinical Trial. Neurocrit Care 2021;epublished September 13th
3. Evered. Anaesthetic depth and delirium after major surgery: a randomised clinical trial. Br J Anaesth 2021;epublished August 28th
4. Meiser. Inhaled isoflurane via the anaesthetic conserving device versus propofol for sedation of invasively ventilated patients in intensive care units in Germany and Slovenia: an open-label, phase 3, randomised controlled, non-inferiority trial. Lancet Respir Med 2021;epublished August 26th
5. Blackwood. Effect of a Sedation and Ventilator Liberation Protocol vs Usual Care on Duration of Invasive Mechanical Ventilation in Pediatric Intensive Care Units: A Randomized Clinical Trial (SANDWICH). JAMA 2021;326(5):401-410
6. Rood. The Impact of Nursing Delirium Preventive Interventions in the Intensive Care Unit: A Multicenter Cluster Randomized Controlled Trial (UNDERPIN-ICU). Am J Resp Crit Care Med 2021;epublished June 25th
7. Roquilly. Effect of Continuous Infusion of Hypertonic Saline vs Standard Care on 6-Month Neurological Outcomes in Patients With Traumatic Brain Injury. The COBI Randomized Clinical Trial. JAMA 2021;325(20):2056-2066
8. Langezaal. Endovascular Therapy for Stroke Due to Basilar-Artery Occlusion. N Engl J Med 2021;384:1910-1920
9. Engelter. Aspirin versus anticoagulation in cervical artery dissection (TREAT-CAD): an open-label, randomised, non-inferiority trial. Lancet Neurology 2021;20(5):341-350
10. Vourc’h, Effect of High-Dose Baclofen on Agitation-Related Events Among Patients With Unhealthy Alcohol Use Receiving Mechanical Ventilation. A Randomized Clinical Trial. JAMA 2021;325(8):732-74
11. Hui. Safety and efficacy of long-term mild hypothermia for severe traumatic brain injury with refractory intracranial hypertension (LTH-1): A multicenter randomized controlled trial, EClinicalMedicine 2021;epublished January 28th

Observational Studies

1. Robba. Intracranial pressure monitoring in patients with acute brain injury in the intensive care unit (SYNAPSE-ICU): an international, prospective observational cohort study. Lancet Neurology 2021;20(7):548-558

1. 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;epublished November 30th
2. 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
3. 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
4. Desch. Angiography after Out-of-Hospital Cardiac Arrest without ST-Segment Elevation. N Engl J Med 2021;epublished August 29th
5. Zampieri. Effect of Slower vs Faster Intravenous Fluid Bolus Rates on Mortality in Critically Ill Patients. The BaSICS Randomized Clinical Trial. JAMA 2021;epublished August 10th
6. Zampieri. Effect of Intravenous Fluid Treatment With a Balanced Solution vs 0.9% Saline Solution on Mortality in Critically Ill Patients. The BaSICS Randomized Clinical Trial. JAMA 2021;epublished August 10th
7. Mathew. Milrinone as Compared with Dobutamine in the Treatment of Cardiogenic Shock. N Engl J Med 2021;385:516-525
8. Dankiewicz. Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest. N Engl J Med 2021;384:2283-2294
9. Azeli. Clinical outcomes and safety of passive leg raising in out-of-hospital cardiac arrest: a randomized controlled trial. Crit Care 2021;25:176
10. Ducrocq. Effect of a Restrictive vs Liberal Blood Transfusion Strategy on Major Cardiovascular Events Among Patients With Acute Myocardial Infarction and AnemiaThe REALITY Randomized Clinical Trial. JAMA 2021;325(6):552-560
11. Holmberg. Ubiquinol (reduced Coenzyme Q10) as a Metabolic Resuscitator in Post-Cardiac Arrest: A Randomized, Double-Blind, Placebo-Controlled Trial. Resuscitation 2021;epublished February 8th
12. Parke. A Multicenter, Open-Label, Randomized Controlled Trial of a Conservative Fluid Management Strategy Compared With Usual Care in Participants After Cardiac Surgery. The Fluids After Bypass Study. Crit Care Med 2021;epublished January 28th

Intubation

1. Matchett. Etomidate versus ketamine for emergency endotracheal intubation: a randomized clinical trial. Intensive Care Med 2021;epublished December 14th
2. 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
3. Jaber. Effect of the use of an endotracheal tube and stylet versus an endotracheal tube alone on first-attempt intubation success: a multicentre, randomised clinical trial in 999 patients. Intensive Care Med 2021;epublished May 25th
4. Sjöblom. Pre-oxygenation using high-flow nasal oxygen vs. tight facemask during rapid sequence induction. Anaesthesia 2021;epublished February 18th

Observational Study

1. Russotto. Intubation Practices and Adverse Peri-intubation Events in Critically Ill Patients From 29 Countries. JAMA 2021;325(12):1164-1172

1. Osman. Helmet continuous positive airway pressure vs. high flow nasal cannula oxygen in acute cardiogenic pulmonary oedema: a randomized controlled trial. Eur Heart J Acute Cardiovasc Care 2021;10(10):1103-1111
2. Johansson. Prostacyclin in Mechanically Ventilated Patients with COVID-19 and Severe Endotheliopathy: A Multicenter, Randomized, Clinical Trial. Am J Respir Crit Care Med 2021;epublished November 23rd
3. Andreu. Comparison of Two Extubation Techniques in Critically Ill Adult Subjects: The ExtubAR Randomized Clinical Trial. Respir Care 2021;epublished November 3rd
4. Osman. Helmet continuous positive airway pressure vs. high flow nasal cannula oxygen in acute cardiogenic pulmonary oedema: a randomized controlled trial. Eur Heart J: Acute Cardiovascular Care 2021;zuab078
5. Johnstone. Effect of Probiotics on Incident Ventilator-Associated Pneumonia in Critically Ill Patients. A Randomized Clinical Trial. JAMA 2021;326(11):1024-1033
6. 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
7. Tavernier. Inhaled amikacin versus placebo to prevent ventilator-associated pneumonia: the AMIKINHAL double-blind multicentre randomised controlled trial protocol. BMJ Open 2021;11(9):e048591
8. 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
9. Ehrmann. Awake prone positioning for COVID-19 acute hypoxaemic respiratory failure: a randomised, controlled, multinational, open-label meta-trial. Lancet Respir Med 2021;epublished August 20th
10. Tongyoo. High-flow nasal oxygen cannula vs. noninvasive mechanical ventilation to prevent reintubation in sepsis: a randomized controlled trial. Ann Intensive Care 2021;11:135
11. 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
12. 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
13. 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
14. He. Early individualized positive end-expiratory pressure guided by electrical impedance tomography in acute respiratory distress syndrome: a randomized controlled clinical trial. Crit Care 2021;25(1):230
15. PRISM trial group. Postoperative continuous positive airway pressure to prevent pneumonia, re-intubation, and death after major abdominal surgery (PRISM): a multicentre, open-label, randomised, phase 3 trial. Lancet Respir Med 2021;epublished June 18th
16. Nguyen. Low Tidal Volume Mechanical Ventilation Against No Ventilation During Cardiopulmonary Bypass in Heart Surgery (MECANO). Chest 2021;159(5):1843-1853
17. Maitland. Randomised controlled trial of oxygen therapy and high-flow nasal therapy in African children with pneumonia (COAST trial). Intensive Care Med 2021;epublished May 5th
18. Nguyen. Low Tidal Volume Mechanical Ventilation Against No Ventilation During Cardiopulmonary Bypass in Heart Surgery (MECANO). Chest 2021;159(5):1843-1853
19. Casey. Protocolized Post-Extubation Respiratory Support to Prevent Reintubation: A Randomized Clinical Trial. Am J Respir Crit Care Med 2021;epublished April 1st
20. Schjørring. Lower or Higher Oxygenation Targets for Acute Hypoxemic Respiratory Failure. N Engl J Med 2021;epublished January 20th

Observational Study

1. Burns. Ventilator Weaning and Discontinuation Practices for Critically Ill Patients. JAMA 2021;325(12):1173-1184

1. Charoensareerat. Efficacy and Safety of Enteral Erythromycin Estolate in Combination With Intravenous Metoclopramide vs Intravenous Metoclopramide Monotherapy in Mechanically Ventilated Patients With Enteral Feeding Intolerance: A Randomized, Double-Blind, Controlled Pilot Study. JPEN J Parenter Enteral Nutr 2021;45(6):1309-1318
2. Boxhoorn. Immediate versus Postponed Intervention for Infected Necrotizing Pancreatitis. N Engl J Med 2021;385:1372-1381
3. Deane. A multicenter randomized clinical trial of pharmacological vitamin B1 administration to critically ill patients who develop hypophosphatemia during enteral nutrition (The THIAMINE 4 HYPOPHOSPHATEMIA trial). Clin Nutr 2021;40(8):5047-5052

1. Philips. Comparison of 5% human albumin and normal saline for fluid resuscitation in sepsis induced hypotension among patients with cirrhosis (FRISC study): a randomized controlled trial. Hepatol Int 2021;epublished May 25th
2. Wong. Terlipressin plus Albumin for the Treatment of Type 1 Hepatorenal Syndrome. N Engl J Med 2021; 384:818-828
3. China. A Randomized Trial of Albumin Infusions in Hospitalized Patients with Cirrhosis. N Engl J Med 2021;384:808-817

Renal Replacement Therapy

1. Vaara. Restrictive fluid management versus usual care in acute kidney injury (REVERSE-AKI): a pilot randomized controlled feasibility trial. Intensive Care Med 2021;epublished May 7th
2. Gaudry. Comparison of two delayed strategies for renal replacement therapy initiation for severe acute kidney injury (AKIKI 2): a multicentre, open-label, randomised, controlled trial. Lancet 2021;397(10281):1293-1300

Deresuscitation / Fluid Balance

1. Silversides. Feasibility of conservative fluid administration and deresuscitation compared with usual care in critical illness: the Role of Active Deresuscitation After Resuscitation-2 (RADAR-2) randomised clinical trial. Intensive Care Med 2021;epublished December 16th
2. Luckraz. Reduction in acute kidney injury post cardiac surgery using balanced forced diuresis: a randomized, controlled trial. Eur J Cardiothorac Surg 2021;59(3):562-569

1. Labro. Impact on antimicrobial consumption of procalcitonin-guided antibiotic therapy for pneumonia/pneumonitis associated with aspiration in comatose mechanically ventilated patients: a multicenter, randomized controlled study. Ann Intensive Care 2021;11:145
2. Dale. Effect of oral chlorhexidine de-adoption and implementation of an oral care bundle on mortality for mechanically ventilated patients in the intensive care unit (CHORAL): a multi-center stepped wedge cluster-randomized controlled trial. Intensive Care Med 2021;epublished October 5th
3. Duyu. Chlorhexidine-impregnated dressing RCT for central-line associated bloodstream infection in critically-ill pediatric patients. Pediatr Int 2021;epublished October 5th
4. Laterre. Safety and tolerability of non-neutralizing adrenomedullin antibody adrecizumab (HAM8101) in septic shock patients: the AdrenOSS-2 phase 2a biomarker-guided trial. Intensive Care Med 2021;epublished October 4th
5. Garbero. High dose coupled plasma filtration and adsorption in septic shock patients. Results of the COMPACT-2: a multicentre, adaptive, randomised clinical trial. Intensive Care Med 2021;epublished October 3rd
6. Evans. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med 2021;epublished October 2nd
7. Laterre. Safety and tolerability of non-neutralizing adrenomedullin antibody adrecizumab (HAM8101) in septic shock patients: the AdrenOSS-2 phase 2a biomarker-guided trial. Intensive Care Med 2021;epublished October 4th
8. Garbero. High dose coupled plasma filtration and adsorption in septic shock patients. Results of the COMPACT-2: a multicentre, adaptive, randomised clinical trial. Intensive Care Med 2021;epublished October 3rd
9. Yu. Effectiveness of anisodamine for the treatment of critically ill patients with septic shock: a multicentre randomized controlled trial. Crit Care 2021;25:349
10. François. Efficacy and safety of suvratoxumab for prevention of Staphylococcus aureus ventilator-associated pneumonia (SAATELLITE): a multicentre, randomised, double-blind, placebo-controlled, parallel-group, phase 2 pilot trial. Lancet Infect Dis 2021;epublished April 21st
11. Rickard. Effect of infusion set replacement intervals on catheter-related bloodstream infections (RSVP): a randomised, controlled, equivalence (central venous access device)–non-inferiority (peripheral arterial catheter) trial. Lancet 2021;397(10283):1447-1458
12. Sehgal. A randomized trial of Mycobacterium w in severe presumed Gram-negative sepsis (MIST). Chest 2021;epublished April 11th
13. Sevransky. Effect of Vitamin C, Thiamine, and Hydrocortisone on Ventilator- and Vasopressor-Free Days in Patients With SepsisThe VICTAS Randomized Clinical Trial. JAMA 2021;325(8):742-750
14. Kyriazopoulou. Procalcitonin to Reduce Long-Term Infection-associated Adverse Events in Sepsis. A Randomized Trial. Am J Respir Crit Care Med 2021;202(3):202–210
15. Wittermans. Adjunctive treatment with oral dexamethasone in non-ICU patients hospitalised with community-acquired pneumonia: A randomised clinical trial. Eur Respir J 2021;epublished January 14th

1. Kulvatunyou. The small (14 Fr) percutaneous catheter (P-CAT) versus large (28–32 Fr) open chest tube for traumatic hemothorax: A multicenter randomized clinical trial. J Trauma Acute Care Surg 2021;91(5):809-813

General

1. Schell. Essential Emergency and Critical Care: a consensus among global clinical experts. BMJ Global Health 2021;6:e006585
2. McHugh. Effects of nurse-to-patient ratio legislation on nurse staffing and patient mortality, readmissions, and length of stay: a prospective study in a panel of hospitals. Lancet 2021;epublished May 11th
3. Robin. Information Pamphlet Given to Relatives During the End-of-Life Decision in the ICU. An Assessor-Blinded, Randomized Controlled Trial. Chest 2021;159(6):2301-2308
4. Chang. Evaluation of Time-Limited Trials Among Critically Ill Patients With Advanced Medical Illnesses and Reduction of Nonbeneficial ICU Treatments. JAMA Intern Med 2021;epublished April 12th
5. Dhanani. Resumption of Cardiac Activity after Withdrawal of Life-Sustaining Measures. N Engl J Med 2021; 384:345-352

End-of-Life

1. van Esch. Effect of Prophylactic Subcutaneous Scopolamine Butylbromide on Death Rattle in Patients at the End of LifeThe SILENCE Randomized Clinical Trial. JAMA 2021;326(13):1268-1276

Endocrine

1. Ramanan. Sodium chloride or Plasmalyte-148 evaluation in severe diabetic ketoacidosis (SCOPE-DKA): a cluster, crossover, randomized, controlled trial. Intensive Care Med 2021;epublished October 5th
2. Bohé. Individualised versus conventional glucose control in critically-ill patients: the CONTROLING study—a randomized clinical trial. Intensive Care Med 2021;epublished September 29th

Perioperative

1. de Waal. Perioperative goal-directed therapy in high-risk abdominal surgery. A multicenter randomized controlled superiority trial. J Clin Anesth 2012;75:110506
2. Diaper. Goal-directed hemodynamic therapy versus restrictive normovolemic therapy in major open abdominal surgery: A randomized controlled trial. Surgery 2021;169(5):1164-1174
3. Asehnoune. Effect of dexamethasone on complications or all cause mortality after major non-cardiac surgery: multicentre, double blind, randomised controlled trial. BMJ 2021;373:n1162
4. Whitlock. Left Atrial Appendage Occlusion during Cardiac Surgery to Prevent Stroke. N Engl J Med 2021;epublished May 15th

Observational Studies

1. McHugh. Effects of nurse-to-patient ratio legislation on nurse staffing and patient mortality, readmissions, and length of stay: a prospective study in a panel of hospitals. Lancet 2021;epublished May11th