Date: 21st May 2012
Here you are a list of must-know landmark studies in Critical Care Medicine to date. Click Read More.

1. Neurology
(i) Dexamethasone in adults with bacterial meningitis. European Dexamethasone in Adulthood Bacterial Meningitis Study Investigators. N Engl J Med. 2002 Nov 14;347(20):1549-56.
(ii) A comparison of four treatments for generalized convulsive status epilepticus. Veterans Affairs Status Epilepticus Cooperative Study Group. N Engl J Med. 1998 Sep 17;339(12):792-8.
(iii) Thrombolysis with alteplase 3-4.5 h after acute ischaemic stroke (SITS-ISTR): an observational study. Lancet. 2008 Oct 11;372(9646):1303-9.
(iv) Surgical decompression for space-occupying cerebral infarction (the Hemicraniectomy After Middle Cerebral Artery infarction with Life-threatening Edema Trial [HAMLET]): a multicentre, open, randomised trial. Lancet Neurol, 8 (2009), pp. 326–33


2. Respiratory
(i) Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med. 1998 Feb 5;338(6):347-54.
(ii) Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med. 2000 May 4;342(18):1301-8
(iii) Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network. N Engl J Med. 2006 Apr 20;354(16):1671-84.
(iv) Neuromuscular Blockers in Early Acute Respiratory Distress Syndrome. ACURASYS Study Investigators. N Engl J Med 2010; 363:1107-1116
(v) 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 Oct 17;374(9698):1351-63.
(vi) Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awakening and Breathing Controlled trial): a randomised controlled trial. Lancet. 2008 Jan 12;371(9607):126-34.
(vii) Effect of intravenous β-2 agonist treatment on clinical outcomes in acute respiratory distress syndrome (BALTI-2): a multicentre, randomised controlled trial. Lancet. 2012 Jan 21;379 (9812):229 – 235


3. Cardiovascular
(i) A Comparison of Albumin and Saline for Fluid Resuscitation in the Intensive Care Unit. The SAFE Study Investigators. N Engl J Med 2004;350:2247-56.
(ii) Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. The Hypothermia after Cardiac Arrest Study Group. N Engl J Med 2002;346:549-556
(iii) Compression-Only CPR or Standard CPR in Out-of-Hospital Cardiac Arrest. Engl J Med 2010; 363:434-442
(iv) Vasopressin and Epinephrine vs. Epinephrine Alone in Cardiopulmonary Resuscitation. N Engl J Med 2008; 359(1):21-30
(v) Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism. N Engl J Med 2002;347:1143-1150
(vi) Comparison of Dopamine and Norepinephrine in the Treatment of Shock. The SOAP II Investigators. N Engl J Med 2010; 362:779-789
(vii) Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med 2008;358:877-887
(viii) Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: a randomised trial. Lancet. 2007 Aug 25;370(9588):676-84.
(ix) The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med 1999;341:709-717
(x) B-CONVINCED: Beta-blocker CONtinuation Vs. INterruption in patients with Congestive heart failure hospitalizED for a decompensation episode. Eur Heart J 2009;30:2186-2192
(xi) Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med 2005;352:225-237
(xii) Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. The SOLVD Investigators. N Engl J Med 1991;325:293-302
(xiii) Early revascularization in acute myocardial infarction complicated by cardiogenic shock. SHOCK Investigators. Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock. N Engl J Med. 1999 Aug 26;341(9):625-34.


4. Gastroenterology
(i) A comparison of sucralfate and ranitidine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group. N Engl J Med. 1998 Mar 19;338(12):791-7.


5. Hepatology
(i) Early Use of TIPS in Patients with Cirrhosis and Variceal Bleeding. The Early TIPS Cooperative Study Group. N Engl J Med 2010; 362:2370-2379
(ii) Terlipressin and albumin vs albumin in patients with cirrhosis and hepatorenal syndrome: a randomized study. Gastroenterology 2008;134:1352-1359


6. Renal
(i) Intensity of Continuous Renal-Replacement Therapy in Critically Ill Patients. The RENAL Replacement Therapy Study Investigators. N Engl J Med 2009; 361:1627-163
(ii) Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: a prospective randomized trial. Lancet 2000;355:26-30
(iii) Intensity of renal support in critically ill patients with acute kidney injury. N Engl J Med 2008;359:7-20
(iv) Intensity of Renal Support in Critically Ill Patients with Acute Kidney Injury. The VANIH Acute Renal Failure Trial Network. N Engl J Med 2008; 359(1):7-20
(v) 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 Dec 23-30;356(9248):2139-43.


7. Endocrine
(i) Intensive Insulin Therapy in Critically Ill Patients. N Engl J Med 2001;345:1359-1367
(ii) Intensive insulin therapy in the medical ICU. N Engl J Med 2006;354:449-461
(iii) Intensive versus conventional glucose control in critically ill patients. The NICE-SUGAR Study Investigators. N Engl J Med 2009;360:1283-1297
(iv) Hydrocortisone therapy for patients with septic shock. CORTICUS Study Group. N Engl J Med 2008;358:111-124
(v) Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA. 2002 Aug 21;288(7):862-71.


8. Haematology
(i) Safety of Recombinant Activated Factor VII in Randomized Clinical Trials. N Engl J Med 2010; 363:1791-1800
(ii) A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. N Engl J Med. 1999 Feb 11;340(6):409-17


9. Rheumatology
(i) Rituximab versus Cyclophosphamide for ANCA-Associated Vasculitis. RAVE−ITN Research Group. N Engl J Med 2010; 363:221-232


10. Nutrition
(i) Early versus Late Parenteral Nutrition in Critically Ill Adults. N Engl J Med 2011;365:506-17
(ii) Does enteral nutrition compared to parenteral nutrition result in better outcomes in critically ill adult patients? A systematic review of the literature. Nutrition 2004;20:843– 848
(iii) Immunonutrition in critically ill patients: a systematic review and analysis of the literature. Intensive Care Med (2008) 34:1980–1990


11. Infection
(i) A randomized trial of diagnostic techniques for ventilator-associated pneumonia. he Canadian Critical Care Trials Group. N Engl J Med 2006;355:2619-2630
(ii) Invasive and noninvasive strategies for management of suspected ventilator-associated pneumonia: a randomized trial. Ann Intern Med 2000;132:621-630
(iii) Predictors of 30-day mortality and hospital costs in patients with ventilator-associated pneumonia attributed to potentially antibiotic-resistant gram-negative bacteria. Chest 2008;134:281-287
(iv) Comparison of 8 versus 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. AMA 2003;290:2588-2598
(v) An intervention to decrease catheter-related bloodstream infections in the ICU. N Engl J Med 2006;355:2725-2732
(vi) Randomized trial of combination versus monotherapy for the empiric treatment of suspected ventilator-associated pneumonia. Crit Care Med 2008;36:737-744
(vii) Severe 2009 H1N1 Influenza in Pregnant and Postpartum Women in California. The California Pandemic (H1N1) Working Group. N Engl J Med 2010; 362:27-35
(viii) Efficacy and safety of recombinant human activated protein C for severe sepsis. Prospective Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study. N Engl J Med 2001;344:699-709
(ix) Drotrecogin alfa (activated) administration across clinically important subgroups of patients with severe sepsis. Crit Care Med 2003;31:12-19
(x) Drotecogin alfa (activated) for adult patients with severe sepsis and a low risk of death. N Engl J Med 2005;353:1332-1341
(xi) Decontamination of the digestive tract and oropharynx in ICU patients. N Engl J Med. 2009 Jan 1;360(1):20-31.
(xii) Early goal-directed therapy in the treatment of severe sepsis and septic shock. Early Goal-Directed Therapy Collaborative Group. N Engl J Med. 2001 Nov 8;345(19):1368-77.
(xiii) Prevention of nosocomial infection in cardiac surgery by decontamination of the nasopharynx and oropharynx with chlorhexidine gluconate. A Randomized Controlled Trial. JAMA. 2006;296:2460-2466
(xiv) Use of procalcitonin to reduce patients' exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial. PRORATA trial group. Lancet. 2010 Feb 6;375(9713):463-74.


12. Trauma
(i) Decompressive Craniectomy in Diffuse Traumatic Brain Injury. DECRA Trial Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group. N Engl J Med 2011; 364:1493-1502
(ii) Administration of methylprednisolone for 24 or 48 hours or tirilazad mesylate for 48 hours in the treatment of acute spinal cord injury. Results of the Third National Acute Spinal Cord Injury Randomized Controlled Trial. JAMA. 1997 May 28;277(20):1597-60
(iii) Very early hypothermia induction in patients with severe brain injury (the National Acute Brain Injury Study: Hypothermia II): a randomised trial. Lancet Neurol. 2011 Feb;10(2):131-9.
(iv) 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 Jul 3;376(9734):23-32.


13. Surgery
(i) Endovascular Repair of Aortic Aneurysm in Patients Physically Ineligible for Open Repair. The United Kingdom EVAR Trial Investigators. N Engl J Med 2010; 362:1872-1880


14. General
(i) Hyperbaric Oxygen for Acute Carbon Monoxide Poisoning. N Engl J Med 2002; 347:1057-1067
(ii) Assessment of the clinical effectiveness of pulmonary artery catheters in management of patients in intensive care (PAC-Man): a randomised controlled trial. PAC-Man study collaboration. Lancet. 2005 Aug 6-12;366(9484):472-7.
(iii) Introduction of the medical emergency team (MET) system: a cluster-randomised controlled trial. Lancet. 2005 Jun 18-24;365(9477):2091-7.