Top 100 Contemporary

Critical Care Studies

These contemporary studies have been chosen based on the significance of the question addressed, methodology,  results, and ability to withstand critique and discussion. Interventions affecting larger numbers of patients are likely to rank higher than niche interventions. Interventional studies which change or confirm practice tend to be placed higher than epidemiological studies, unless of a very major nature. Basing such a list on citations alone would generate a lead time bias. These views are mine, and this list will change as new evidence emerges, corrections are pointed out, and as I add studies I have accidentally overlooked. The broad positioning of a study is probably more informative than than its absolute position, with placement within the top, middle and bottom thirds a more accurate reflection, especially outside the top 20 placings. Please feel free to disagree and email your suggested changes and why. The order of this list has been last updated May 15th 2014, with study summaries being added regularly.


For more in-depth appraisals of many major critical care studies, visit The Bottom Line, a website produced by the Steve Mathieu, Duncan Chambler and David Slessor from Portsmouth, and the WESSEX Intensive Care Society.

Studies 1-10

1-10   11-20   21-30   31-40   41-50   51-60   61-70   71-80   81-90   91-100

  1. 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
    • In a randomized controlled trial of 861 patients with ARDS, mechanical ventilation with a tidal volume of 6 ml/kg and plateau pressure ≤ 30 cmH20, in comparison with tidal volume of 12 ml/kg and plateau pressure ≤ 50cm H20, was associated with a 9% absolute mortality decrease (31% vs 40%, P=0.007; NNT=11) and a 2 day increase in ventilator-free days (12±11 vs. 10±11; P=0.007).
  2. Finfer. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med 2004;350(22):2247-56
    • In a  multicenter, randomized, double-blind trial comparing 0.9% saline or 4% albumin for fluid resuscitation in 6997 critically ill patients in the ICU, there was no difference in mortality (729 v 726, RR 0.99; 95 CI 0.91 to 1.09; P=0.87), new single-organ and multiple-organ failure (P=0.85), mean (SD) numbers of ICU days (6.2±6.2 v 6.5±6.6, P=0.44), hospital days (15.6±9.6 v 15.3±9.6; P=0.30), days of mechanical ventilation (4.3±5.7 v 4.5±6.1; P=0.74), or days of renal-replacement therapy (0.4±2.0 v 0.5±2.3) respectively.
  3. Hebert. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. N Engl J Med 1999;340:409-17
    • In a randomized controlled trial comparing a red cell transfusion trigger of 7 g/dL versus 10 g/dl in 838 critically ill resuscitated patient, there was no difference in either total 30 day mortality (18.7% vs 23.3%, P=0.11, respectively) or mortality in those with clinically significant cardiac disease (20.5% vs 22.9%; P=0.69). The restrictive transfusion policy was superior for mortality outcome in patients with APACHE II scores of <20 (8.7% vs 16.1%;P=0.03), in patients < 55 years of age (5.7% vs 13.0%; P=0.02), and during hospitalization (22.2% vs 28.1%;P=0.05).
  4. Myburgh. Hydroxyethyl Starch or Saline for Fluid Resuscitation in Intensive Care (CHEST study). NEJM 2012;367:1901-1911
    • In a blinded randomized controlled trial comparing 6% hydroxyethyl starch 130/0.42 (Voluven) with 0.9% saline for fluid resusciation in 7000 critically ill patients, this colloid therapy was associated with a 21% increased risk of the requirement for renal replacement therapy ( HES RRT requirement 7.0% versus saline 5.8%; relative risk 1.21; 95% CI 1.00 to 1.45; P=0.04 and no mortality benefit (HES mortality 18.0% versus  saline mortality 17.0%; relative risk in the HES group, 1.06; 95% CI 0.96 to 1.18; P=0.26). Starch therapy was also associated with increased rates of hepatic failure, rash and pruritus.
  5. Perner. Hydroxyethyl Starch 130/0.4 versus Ringer's Acetate in Severe Sepsis. (6S Trial). N Eng J Med 2012;367:124-134
    • In a blinded randomized controlled trial comparing 6% hydroxyethyl starch 130/0.42 (Tetraspan) with Ringers acetate for fluid resuscitation in 804 patients with severe sepsis, at 90 days the use of HES was associated with an 8% absolute increase in mortality (51% v 43%; relative risk: 1.17; 95% CI: 1.01 to 1.36; P=0.03) and a 6% absolute increase in renal replacement therapy (22% v 16%; relative risk: 1.35; 95% CI 1.01 to 1.80; P=0.04).
  6. Kress. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med 2000;342:1471-7
    • In a single centre, randomised, controlled trial comparing daily sedation hold with continuous sedation in 128 critically ill mechanically ventilated adults, sedation hold decreased the median durations of mechanical ventilation (4.9 days versus 7.3, p=0.004) and ICU length of stay (6.4 days versus 9.9 days, p = 0.02) as well as the requirement for diagnostic testing for changes in mental status (9% versus 27%, p = 0.02). There were no significant differences in adverse events, including self extubation (intervention group 4% versus control group 7 %, p = 0.88). 
  7. NICE-SUGAR Study Investigators. Intensive versus Conventional Glucose Control in Critically Ill Patients. N Engl J Med 2009;360:1283-97
    • In a multicentre, randomized controlled trial comparing intensive glucose control (81-108 mg/dL / 4.5-6.0 mmol/L) with conventional glucose control (≤180 mg/dL / ≤ 10.0 mmol/L) in 6,104 adult medical and surgical patients, intensive glucose control increased mortality (27.5% vs 24.9%; odds ratio 1.14; 95% CI 1.02 to 1.28; P=0.02). There was no significant difference between medical and surgical patients (odds ratio 1.31 and 1.07 respectively; P=0.10). Severe hypoglycaemic episodes (blood glucose level ≤40mg/dL / 2.2 mmol/L) were more common in the intensive glucose control group (6.8% vs 0.5%; P<0.001). There were no significant differences in the median number of days of mechanical ventilation (P=0.56) or renal-replacement therapy (P=0.39), or days in ICU (P=0.84) or hospital (P=0.86). 
  8. 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
    • In a multicentre, randomised, controlled, double-blind study comparing low-dose dopamine (2μg/kg/min) infusion with placebo in 328 patients with at least two SIRS criteria and early renal dysfunction, there were no differences in peak serum creatinine concentration (dopamine 245 vs placebo 249 μmol/L; p=0·93), increase in serum creatinine from baseline to highest value (62 vs 66 μmol/L; p=0·82), patients whose serum creatinine concentration exceeded 300 μmol/L (56 vs 56; p=0·92), requirement for renal replacement therapy (35 vs 40; p=0·55), duration of ICU stay (13 vs 14 days; p=0·67), duration of hospital stay (29 vs 33 days; p=0·29), or mortality (69 deaths versus 66 deaths).
  9. Nielsen. Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest. N Engl J Med 2013;369:2197-2206
    • In a multicenter, randomized, control trial, comparing temperature management at 33°C with 36°C in 939 comatose patients after out-of-hospital cardiac arrest of presumed cardiac cause, there was no difference in mortality at the end of the trial (33°C group 50% vs 36°C group 48%; hazard ratio with 33°C, 1.06; 95% CI 0.89 to 1.28; P = 0.51), 180-day composite of mortality and poor neurological function (54% vs. 52%, respectively; RR 1.02; 95% CI 0.88 to 1.16; P = 0.78), or serious adverse events (93% vs. 90%, respectively; RR 1.03; 95% CI 1.00 to 1.08; P = 0.09).
  10. Prasad. A Decade of Reversal: An Analysis of 146 Contradicted Medical Practices. Mayo Clinic Proceedings 2013;88(8):790-798
    • Prasad et al reviewed 2,044 original articles published from 2001 to 2010 in the New England Journal of Medicine, and found of 1,344 articles which investigated a medical practice, 73.0% examined a new medical practice, and 27.0% tested an established practice; while 70.5% had positive findings, and 29.5% had negative findings. Of the 1,344 articles addressing a medical practice, 56% demonstrated a new practice surpassed a standard of care, 12% demonstrated a new practice was no better than current practice, 11% showed an existing practice was no better than a lesser therapy, 10% showed an existing practice was better than a lesser standard, while 10% were inconclusive. Of the 363 articles testing standard of care, 146 (40.2%) reversed that practice, whereas 138 (38.0%) reaffirmed it.
    • Studies 11 - 20
    • 1-10   11-20   21-30   31-40   41-50   51-60   61-70   71-80   81-90   91-100
  11. Sprung. Hydrocortisone Therapy for Patients with Septic Shock. N Engl J Med 2008;358:111-124
    • In a multicentre, double-blind, randomized placebo-controlled trial comparing hydrocortisone (50mg IV 6 hourly, then tapered) with placebo in 499 patients with septic shock, there was no significant difference in 28-day mortality (hydrocortisone group 34.3% vs placebo group 31.5%; P=0.51). Subgroup analyses of 28-day mortality based on response to corticotropin also showed no difference between study groups. Hydrocortisone hastened reversal of shock compared to placebo, however, with more episodes of superinfection, including new sepsis and septic shock.
  12. Guérin. Prone Positioning in Severe Acute Respiratory Distress Syndrome (PROSEVA). New Engl J Med 2013; 368:2159-2168
    • In a multicentre, randomised control trial, comparing prolonged periods of prone position ventilation with ongoing supine position ventilation, in 466 patients with moderate-to-severe ARDS, prone positioning was associated with reduced 28 day mortality (16% versus 32.8%, hazard ratio 0.39, 95% CI 0.25 to 0.63, P<0.001), reduced 90 day mortality (23.6% versus 41%, HR 0.44, 95% CI 0.29 to 0.67, P<0.001), and less cardiac arrests (31 patients versus 16 patients, P=0.02), with no difference in other complications.
  13. de Jonge. Effects of selective decontamination of the digestive tract on mortality and acquisition of resistant bacteria in intensive care: a randomised controlled trial. Lancet 2003;362:1011-1016  (abstract)
    • In an unblinded, single center, randomized control trial comparing selective digestive tract decontamination (oral and enteral polymyxin E, tobramycin, and amphotericin B combined with an initial 4-day course of intravenous cefotaxime) with standard treatment in 934 critically ill patients, SDD was associated with reductions in ICU mortality (15% versus 23%, P=0.002), hospital mortality (24% versus 31%, P=0.02) and colonization with resistant gram-negative bacteria (16% versus 26%, P=0.001), with equal colonization of vancomycin resistant enterococcus (1% versus 1% p=1.0) and absence of methicillin resistant staphylococcus aureus colonization.
  14. de Smet. Decontamination of the digestive tract and oropharynx in ICU patients. N Engl J Med. 2009 Jan 1;360(1):20-31
  15. The ProCESS Investigators. A Randomized Trial of Protocol-Based Care for Early Septic Shock (ProCESS study). New Engl J Med 2014;epublished March 18th
  16. 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  (abstract)
    • In a multicenter, randomized control trial comparing critical care management with a pulmonary artery catheter to management without a pulmonary artery catheter in 1,014 general ICU patients, there was no difference in hospital mortality (68% versus 66%, hazard ratio 1.09, 95% CI 0.94 to 1.27, P=0.39) or complications, with the incidence of non-fatal complications secondary to pulmonary artery catheterization being 9.5%.
  17. Maitland. Mortality after Fluid Bolus in African Children with Severe Infection (FEAST Trial). N Engl J Med 2011;364:2483-2495   (Paediatric Study)
    • Maitland et al performed a stratified (severe hypotension or not), multicenter, randomized control trial, in a resource-limited setting in sub-Saharan Africa, comparing a fluid bolus (20 to 40 ml of 5% albumin or 0.9% saline) with no fluid bolus at admission to hospital in 3,141 children with febrile illness and impaired perfusion, and found fluid bolus therapy was associated with a higher mortality at 48 hours (albumin  10.6%, saline 10.5%, no bolus 7.3%; relative risk bolus therapy versus no bolus 1.45, 95% CI 1.13 to 1.86, P=0.003), and 28 days (12.2%, 12.0% & 8.7%, respectively; RR bolus therapy versus no bolus p=0.004), with similar incidences of pulmonary oedema, increased intracranial pressure (2.6%, 2.2% versus 1.7% P=0.17), and neurological sequela in the three groups (P=0.92).
  18. Annane. Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: A randomised trial. Lancet 2007; 370:676-684  (abstract)
    • In a blinded, multicenter, randomized control trial, comparing noradrenaline plus dobutamine with adrenaline in 330 patients with septic shock, aiming to maintain mean arterial pressure at 70 mmHg, there were no significant differences in 28 day mortality (34% vs. 40%, relative risk 0.86, 95% CI 0.65 to 1.14, P=0.31), ICU mortality (47%s vs 75, p=0·69), hospital mortality (52% vs 49%, p=0·51), 90 day mortality (52% vs 50%, p=0·73), time to haemodynamic success (p=0·67), time to vasopressor withdrawal (p=0·09), or rates of serious adverse events.
  19. 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  (abstract)
    • In a multicenter, randomized control trial, comparing ongoing conventional mechanical ventilation in a non-ECMO centre with transfer to an ECMO centre for respiratory support with either conventional mechanical ventilation or ECMO in 180 patients with severe hypoxic respiratory failure, ECMO centre management, where only 75% of the transferred patients actually received ECMO, was associated with increased 6-month survival (63% vs. 47%, relative risk 0.69, 95% CI 0.05 to 0.97, P=0.03) and a gain of 0·03 quality-adjusted life-years at 6-months, with a lifetime model predicting the cost per QALY of ECMO to be £19 252 (95% CI 7622—59 200) at a discount rate of 3·5%
  20. Ranieri. Drotrecogin Alfa (Activated) in Adults with Septic Shock ( PROWESS-SHOCK Study). N Engl J Med 2012;366:2055-206
    • In a blinded, multicenter, randomized, control trial, comparing activated protein C (24 µg/kg/hr for 96 hours) with a placebo, in 1,697 adults with septic shock, there were no significant differences in mortality at 28 (26.4% vs. 24.2%, relative risk with APC 1.09, 95% CI 0.92 to 1.28 P=0.31) or 90 days (34.1% versus 32.7%, relative risk with APC 1.04, 95% CI 0.90 to 1.19, P=0.56), including those with initially low levels of APC (28 day mortality 28.7% vs. 30.8%, RR 0.93, 95% CI 0.74 to 1.17; p=0.54), or difference in serious bleeding (APC 10 patients versus placebo 8 patients, P=0.81).
    • Studies 21 - 30
    • 1-10   11-20   21-30   31-40   41-50   51-60   61-70   71-80   81-90   91-100
  21. 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 
    • In a blinded, international, multicenter, randomized control trial, largely in resource limited healthcare systems, comparing administration of tranexamic acid (TXA) within 8 hours of traumatic injury (1g over 10 min, then infusion of 1g over 8 hours) with placebo in 20,211 adult patients, with or at risk of significant haemorrhage (SBP <90 mmHg or HR >110 bpm, or both), TXA was associated with reduced mortality (14.5% versus 16.0%; relative risk 0.91, 95% CI 0.85 to 0.97; p=0.0035), including reduced bleeding-related mortality (4.9% versus 5.7%; RR 0.85, 95% CI 0.76 to 0.96; p=0.0077), despite no difference in requirement for blood transfusions (50.4% vs. 51.3%) or vascular-occlusive events.  In a subsequent post hoc analysis, the bleeding-related mortality reduction with TXA was time dependent, and actually reversed with late administration after 3 hours of injury (TXA 4.4% vs. placebo 3.1%, p=0.004).
  22. Asfar. High versus Low Blood-Pressure Target in Patients with Septic Shock (SEPSISPAM study). New Engl J Med 2014;370:1583-1593
  23. Casaer. Early versus Late Parenteral Nutrition in Critically Ill Adults. NEJM 2011;365:506-517
    • In a multicenter, randomized trial comparing early parenteral nutrition (within 48 hours of ICU admission) with late parenteral nutrition (within day 8 of ICU admission) to supplement inadequate enteral nutrition, in 4,640 critically ill patients, late parenteral nutrition was associated with multiple improvements, including shorter durations of ICU (3 days vs. 4 days;p=0.02) and hospital (14 vs. 16 days, p=0.004) stay, fewer ICU infections (22.8% vs. 26.2%, P=0.008), lower incidence of cholestasis (P<0.001), reduced requirement for ventilation for > 2 days (36.3% vs. 40.2%, P=0.006), less duration of renal-replacement therapy (7 vs. 10 days, P=0.008) and mean reduction in health care costs of £910 (P=0.04).
  24. 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
    • Doig et al performed a multicenter, randomized trial comparing standard care with early parenteral nutrition in 1,372 critically ill patients with relative contraindications to enteral nutrition remaining in ICU for > 2 days, and found no difference in 60 day mortality (standard care 22.8% vs. early PN 21.5%; risk difference −1.26%; 95% CI −6.6 to 4.1; P = 0.60). Early parenteral nutrition patients required fewer days of mechanical ventilation (7.73 versus 7.26, risk difference −0.47; 95% CI −0.82 to −0.11; P = 0.01), less muscle wasting based on subjective global assessment (0.43 versus 0.27; mean difference −0.16; 95% CI −0.28 to −0.038; P = 0.01) and less fat loss (0.44 versus 0.31; mean difference −0.13; 95% CI −0.25 to −0.01; P = 0.04). Day-60 quality of life (RAND-36 General Health Status) was statistically higher in the early PN group, which was not clinically meaningful. (45.5 versus 49.8; mean difference 4.3; 95% CI 0.95 to 7.58; P = 0.01). 
  25. 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
  26. Girard. 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;371(9607):126-134   (abstract)
    • In a multicentre, randomised controlled trial comparing paired daily sedation hold plus daily spontaneous breathing trial (intervention) versus uninterrupted sedation plus a daily spontaneous breathing trial (control) in 336 sedated, mechanically ventilated patients, the intervention was associated with more days breathing without assistance (14·7 vs 11·6 days; 95% CI 0·7 to 5·6; p=0·02), earlier discharge from both intensive care (median time in ICU 9·1 days vs 12·9 days; p=0·01) and the hospital (median time in the hospital 14·9 days vs 19·2 days; p=0·04), and reduced one-year mortality (HR 0·68; 95% CI 0·50 to 0·92; p=0·01; NNT 7.4, 95% CI 4·2 to 35·5). More patients in the intervention group self-extubated, but with similar rates for both reintubation after self-extubation and total reintubation.
  27. Chesnut. A Trial of Intracranial-Pressure Monitoring in Traumatic Brain Injury. New Engl J Med 2012;367:2471-2481
  28. Caironi. Albumin Replacement in Patients with Severe Sepsis or Septic Shock (ALBIOS study). New Engl J Med 2014;370:1412-1421
  29. Palevsky. Intensity of renal support in critically ill patients with acute kidney injury. N Engl J Med 2008; 359:7-20
  30. Drakulovic. Supine body position as a risk factor for nosocomial pneumonia in mechanically ventilated patients: a randomised trial. Lancet 1999;354(9193):1851–1858 
    • In a single centre, randomized controlled trial comparing semirecumbent with supine body position in 86 mechanically ventilated medical patients, the semirecumbent group had a lower frequency of suspected noscomial pneumonia (8% vs 34%; 95% CI for difference 10·0 to 42.0; P=0·003) and microbiologically confirmed pneumonia (5% vs 23%; 95% CI 4.2 to 31.8; p=0·018). Supine body position (odds ratio 6.8; 95% CI 1.7 – 26.7; P=0·006) and enteral nutrition (odds ration 5.7; 95% CI 1.5 – 22.8; P=0·013) were independent risk factors for nosocomial pneumonia. 
    • Studies 31 - 40
    • 1-10   11-20   21-30   31-40   41-50   51-60   61-70   71-80   81-90   91-100
  31. Mehta. Daily Sedation Interruption in Mechanically Ventilated Critically Ill Patients Cared for With a Sedation Protocol. A Randomized Controlled Trial (SLEAP study). JAMA 2012;308(19):1985-1992
  32. Papazian. Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med 2010;363:1107-1116
    • In a multicentre, double-blind, randomized controlled trial comparing 48 hours of cisatracurium besylate with placebo in 340 patients with early severe ARDS, neuromuscular blockade was associated with a trend for reduced crude 90-day mortality {31.6% (95% CI 25.2 – 38.8) vs 40.7% (95% CI 33.5 – 48.4)} (P=0.08). After adjustment for baseline PaO2:FiO2, plateau pressure and Simplified Acute Physiology II scores, neuromuscular blockade reduced the adjusted hazard ratio for death at 90 days (HR 0.68, 95% CI 0.48 to 0.98; P=0.04). There was no difference in the rate of ICU-acquired paresis.
  33. Jones. Lactate Clearance vs Central Venous Oxygen Saturation as Goals of Early Sepsis Therapy. JAMA 2010;303(8):739-746
  34. COIITSS Study Investigators. Corticosteroid treatment and intensive insulin therapy for septic shock in adults: a randomized controlled trial. JAMA. 2010 Jan 27;303(4):341-8
  35. Russell. Vasopressin versus norepinephrine infusion in patients with septic shock (VASST). NEJM 2008;358:877-87
  36. Davies. A multicenter, randomized controlled trial comparing early nasojejunal with nasogastric nutrition in critical illness (ENTERIC Study). Crit Care Med 2012;40(8):2342-2348
  37. Heyland. A Randomized Trial of Glutamine and Antioxidants in Critically Ill Patients (REDOXS study). N Engl J Med 2013;368:1489-1497
  38. Thiele. Intraaortic Balloon Support for Myocardial Infarction with Cardiogenic Shock (IABP-SHOCK II Trial). NEJM epublished ahead of print August 27th 2012
  39. Wallace. Nighttime Intensivist Staffing and Mortality among Critically Ill Patients. N Engl J Med 2012; 366:2093-2101
  40. Kakkar. Low-Molecular-Weight Heparin and Mortality in Acutely Ill Medical Patients. N Engl J Med 2011; 365:2463-2472
  41. Kumar. Initiation of inappropriate antimicrobial therapy results in a fivefold reduction of survival in human septic shock. Chest 2009; 136(5):1237-1248.
  42. Kumar. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 2006; 34(6): 1589-1596  (abstract)
  43. Chastre. Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. JAMA 2003; 290: 2588- 2598
  44. Bernard. Treatment of Comatose Survivors of Out-of-Hospital Cardiac Arrest with Induced Hypothermia. N Engl J Med 2002; 346:557-563
    • In a multicentre, blinded, randomised, controlled trial comparing therapeutic hypothermia (33°C, achieved within 2 hours of ROSC and maintained for 12 hours) with normothermia in 77 comatose survivors of out-of-hospital VF cardiac arrest, hypothermia improved survival with a good outcome (49% versus 26%, p=0.046; odds ratio 5.25, 95% CI 1.47 to 18.76, p = 0.011). Hypothermia was associated with a lower cardiac index, higher systemic vascular resistance, hyperglycemia, with no difference in the frequency of adverse events.
  45. 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
    • In a multicentre, blinded, randomized, controlled trial comparing therapeutic hypothermia (32°C to 34°C for 24 hours) with normothermia in 273 comatose survivors of out-of-hospital VF/VT, hypothermia improved favourable neurological outcomes (55% vs 39%; RR 1.40, 95% CI 1.08 to 1.81) and 6 month mortality (41% vs 55%; RR 0.74, 95% CI 0.58 to 0.95). The complication rate did not differ significantly between the two groups.
  46. Harris. Universal Glove and Gown Use and Acquisition of Antibiotic-Resistant Bacteria in the ICU: A Randomized Trial. JAMA 2013;epublished October 4th
  47. Huang. Targeted versus Universal Decolonization to Prevent ICU Infection. N Eng J Med 2013;epublished May 29th
  48. Mentzelopoulos. Vasopressin, Steroids, and Epinephrine and Neurologically Favorable Survival After In-Hospital Cardiac Arrest: A Randomized Clinical Trial. JAMA 2013;310(3):270
  49. Strøm. A protocol of no sedation for critically ill patients receiving mechanical ventilation: a randomised trial. Lancet 2010;375(9713):475-480
  50. Stelfox. Intensive Care Unit Bed Availability and Outcomes for Hospitalized Patients With Sudden Clinical Deterioration. Arch Intern Med 2012;epublished ahead of print
  51. Mier. Early versus late necrosectomy in severe necrotzing pancreatitis. Am J Surg 1997;173:71–5
  52. Pitt. The effect of spironolactone on mortality and morbidity in patients with severe heart failure (RALE study). N Engl J Med 1999; 341(10):709-717
  53. Villanueva. Transfusion Strategies for Acute Upper Gastrointestinal Bleeding. N Engl J Med 2013;368:11-21
  54. Meyer. Fibrinolysis for Patients with Intermediate-Risk Pulmonary Embolism (PEITHO study). N Engl J Med 2014;370:1402-1411
  55. 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.
  56. Jakob. Dexmedetomidine vs Midazolam or Propofol for Sedation During Prolonged Mechanical Ventilation: Two Randomized Controlled Trials. JAMA 2012;307(11):1151-1160
  57. Martin. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 2003, 348:1546-1554..
  58. Annane. Corticosteroids in the Treatment of Severe Sepsis and Septic Shock in Adults. JAMA 2009;301(22):2362-2375
  59. Ferguson. High-Frequency Oscillation in Early Acute Respiratory Distress Syndrome (OSCILLATE). New Engl J Med 2013;epublished January 22rd
  60. Young. High-Frequency Oscillation for Acute Respiratory Distress Syndrome (OSCAR). New Engl J Med 2013;epublished January 22nd       
  61. Schortgen. Fever Control Using External Cooling in Septic Shock: a Randomized Controlled Trial. J Respir Crit Care Med 2012;185;10:1088-1095
  62. Young. Effect of Early vs Late Tracheostomy Placement on Survival in Patients Receiving Mechanical Ventilation: The TracMan Randomized Trial. JAMA 2013;309(20):2121
  63. Ranieri. Drotrecogin Alfa (Activated) in Adults with Septic Shock ( PROWESS-SHOCK Study). N Engl J Med 2012;366:2055-206    (abstract) 
  64. Bouadma. Use of procalcitonin to reduce patients' exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomized controlled trial. Lancet. 2010;375:463-474.
  65. Allen. Cerebral Arterial Spasm – A Controlled Trial of Nimodipine in Patients with Subarachnoid Hemorrhage. N Engl J Med 1983; 308:619-624   (abstract) 
  66. 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
  67. Rubertsson. Mechanical Chest Compressions and Simultaneous Defibrillation vs Conventional Cardiopulmonary Resuscitation in Out-of-Hospital Cardiac ArrestThe LINC Randomized Trial. JAMA 2013;epublished November 17th
  68. Dieleman. Intraoperative High-Dose Dexamethasone for Cardiac Surgery - A Randomized Controlled Trial (Dexamethasone for Cardiac Surgery (DECS) Study). JAMA 2012;308(17):1761-1767
  69. Kerlin. A Randomized Trial of Nighttime Physician Staffing in an Intensive Care Unit. New Engl J Med 2013; 368:2201-2209
  70. Schweickert. Early physical and occupational therapy in mechanically ventilated, critically ill patients: A randomised controlled trial. Lancet 2009; 373:1874–1882
  71. Reignier. Effect of Not Monitoring Residual Gastric Volume on Risk of Ventilator-Associated Pneumonia in Adults Receiving Mechanical Ventilation and Early Enteral Feeding:  A Randomized Controlled Trial. JAMA 2013;309(3):249
  72. Ronco. Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: a prospective randomised trial. Lancet 2000;356:26-30
  73. Vincent. International Study of the Prevalence and Outcomes of Infection in Intensive Care Units. JAMA. 2009;302(21):2323-2329
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