Hot Articles

The following articles have been chosen as the most noteworthy publications in critical care since December 2011.


NEJM -Steroids in Septic Shock

NEJM - Saline vs Balanced Crystalloids

NEJM - Saline vs Balanced Crystalloids

JAMA - Bag-Mask Ventilation vs Endotracheal Intubation During CPR in OOHCA

JAMA - On-Demand vs Routine Nebulization of Acetylcysteine With Salbutamol in Ventilated Patients

JAMA - Paediatric Early Warning System

JAMA - Meropenem-Vaborbactam vs Piperacillin-Tazobactam in Complicated UTIs

Acta Anaesthesiologica Scandinavica - Acute Circulatory Failure Inotropy Guideline

JAMA - Haloperidol Prophylaxis for Delirium

Thorax - Rehabilitation Intensity

Lancet Respir Med - Colistin +/- Meropenam in Carbapenam Resistant Gram-negative Infections

Trans R Soc Trop Med Hyg - Septic Shock in Reseource-Limited Settings

J Intensive Care - Japanese Sepsis Guideline

Lancet Infect Dis - Antibiotic Cycling

Lancet Respir Med - Perioperative Ventilation

NEJM - Late Stroke Thrombectomy

Stroke - Ischaemic Stroke Guideline

New Engl J Med - Steroids in Septic Shock

Lancet Respiratory Medicine - Perioperative Ventilation

Lancet Respiratory Medicine - Induced Hypothermia in Septic Shock

Resuscitation - Antibiotics in Survivors of Out-of-Hospital Cardiac Arrest


30th Annual ESICM Congress (LIVES2017, Vienna) 

New Engl J Med - Age of Transfused Red Cells

JAMA - Alveolar Recruitment in ARDS

JAMA - Intra-Operative Blood Pressure Management

JAMA - Systematic ICU Admission for Elderly Sick Patients

JAMA - Early Goal-Directed Sepsis Care in Zambia

Intensive Care Medicine - Early Goal-Directed Nutrition

Intensive Care Medicine - Airway Pressure Release Ventilation

Intensive Care Medicine - Spontaneous Breathing Trials

Intensive Care Medicine - Biomarker-Guided Strategy for Discontinuing Antifungal Therapy

Kneyber. Recommendations for mechanical ventilation of critically ill children from the Paediatric Mechanical Ventilation Consensus Conference (PEMVECC). Intensive Care Med 2017;epublished September 22nd

Intensive Care Medicine - Positioning for VAP

Intensive Care Medicine - Adrenal Insufficiency Guideline

Circulation - Cardiogenic Shock Guideline

Lancet Respiratory Medicine - Sedation Interruption

Chest - Checklists for ICU Intubation

Critical Care Medicine - Nebulized Versus IV Amikacin in VAP

European Respiratory Journal - HAP / VAP Guideline

Annals of Surgery - Transfusion Thresholds in Burns

Critical Care - Loxapine for Agitation

Critical Care - Recombinant ACE 2 in ARDS

J Crit Care - Enteral Nutrition as Stress Prophylaxis

Am J Respir Crit Care Med - Coping Skills in ICU Survivors

European Respiratory Journal - NIV Guideline

NEJM - Oxygen in Acute Myocardial Infarction

Crit Care Resusc - Earplugs for Sleep Quality

Resuscitation - Intermittent vs Continuous Neuromuscular Blockade during Temperature Management post Cardiac Arrest

JAMA - Ganciclovir in CMV-Positive Critically Ill Patients

Critical Care - Serlipressin in Septic Shock

Critical Care Medicine - Simulation for ECMO Emergencies

Critical Care Medicine - Exposure Keratopathy

Critical Care - Software-Guided Glycaemic Control

Thorax - Rehabilitation in the ICU

JAMA - 24 vs 48 Hours of Hypothermia post Cardiac Arrest

JPEN - Paediatric Nutritional Support Guideline

Journal of Intensive Care - Japanese ARDS Guideline

Chinese Medical Journal - EEG Monitoring Guideline

Lancet respiratory Medicine - Simvastatin for Prevention & Treatment of ICU Delirium

Journal of Critical Care - Furosemide in Early Acute Kidney Injury

Lancet - Procalcitonin-Guided Antibiotics in Early Sepsis

Minerva Pneumologica - NIV vs IMV in Hypoxaemic Respiratory Failure

JAMA Cardiology - Spironolactone in Acute Heart Failure

Anaesth Crit Care Pain - French TTM Guideline

World Jounal of Emergency Surgery - Intra-Abdominal Infections Guideline

Critical Care Medicine - Blood flow & CRRT Circuit Lifespan

European Heart Journal - Safety of Mechanical Chest Compression Devices

Journal of Korean medical Science - Mild Hypothermia for Poor Grade Subarachnoid Haemorrhage

Critical Care Medicine - Shenfu Injection post Cardiac Arrest

JAMA - Cooling post Neonatal Hypoxic-Ischaemic Encephalopathy

Circulation - N-Acetylcysteine & Nitrate Therapy in STEMI

Thorax - Post ICU Rehabilitation

McDowell. Effectiveness of an exercise programme on physical function in patients discharged from hospital following critical illness: a randomised controlled trial (the REVIVE trial) Thorax 2017;72:594-595

JAMA - FAST Scan in Paediatric Trauma

J Allergy Clin Immunol Pract - Icatibant for ACE Inhibitor-Induced Angioedema

Ann Emerg Med - High Flow Nasal Oxygen in Cardiogenic Pulmonary Oedema

Critical Care - Supplementary Parenteral Nutrition

JAMA Surgery - Intraoperative Dexmedetomidine & Post-Op Cognitive Dysfunction

Intensive Care Med - AKI Guideline

American Thoracic Society Conference

NEJM - Angiotensin II for Septic Shock

NEJM - Time to Treatment in Sepsis

JAMA - Outcome Prediction ICU

Thorax - BTS Oxygen Use Guideline

Crit Care Medicine - Paediatric & Neonatal Septic Shock Guideline

Neurology - Brain Injury after CPR Guideline

Chest - Positioning for Endotracheal Intubation

Resuscitation - Video versus Direct Laryngoscopy for Paramedic Endotracheal Intubation

European Journal of Anaesthesiology - Severe Perioperative Bleeding Guideline

Annals of Intensive Care - Post Extubation High Flow Nasal Oxygen

Crit Care Medicine - Stress Ulcer Prophylaxis

American Heart Journal - Nitric Oxide in Acute PE

N Eng J Med - Bystander Efforts in Out-of-Hospital Cardiac Arrest

Lancet - Tranexamic Acid for Post Partum Haemorrhage

Lancet Haematology - FFP vs Coagulation Factor Concentrates for Traumatic Coagulopathy

JAMA Internal Medicine - Antiviral Therapy for CMV Reactivation

Annals of Thoracic Surgery - Corticosteroids in Neonatal Cardiac Operations

JAMA - Postoperative Troponin Elevation in Noncardiac Surgery

Intensive Care Medicine - Immunoglobulin for Necrotising Soft Tissue Infection

New England Journal of Medicine - Ularitide in Acute Heart Failure

Intensive Care Medicine - NIV Post Extubation in Chronic Respiratory Disorders

Intensive Care Medicine - IV Chloride Restriction in Cardiac Surgery

Critical Care Medicine - Transfusion in Critically Ill Oncology Patients

J Trauma - Damage Control Resuscitation Guideline

J Crit Care - Tracheostomy Guideline

Intensive Care Med - Condolence Letter

JPEN J Parenter Enteral Nutr - Parenteral Nutrition Guideline

Intensive Care Medicine - Early Enteral Nutrition Guideline

Critical Care Medicine - Contrast-Induced Nephropathy

Critical Care - Pseudomonas Vaccine

Society of Critical Care Medicine Annual Congress

JAMA - Video vs Direct Laryngoscopy for Intubation in ICU

N Engl J Med - Therapeutic Hypothermia for Paediatric Cardiac Arrest

N Engl J Med - Paediatric Glycaemic Control

JAMA - Intubation during Cardiac Arrest

Crit Care Med - Surviving Sepsis Campaign Guidelines

Crit Care Med - Family-Centred Care Guidelines

Chest - Liberation from Mechanical Ventilation Guidelines


NEJM - Age of Transfused Blood

NEJM - Tranexamic Acid for Coronary Artery Surgery

Intensive Care Medicine - High Flow Nasal Oxygen post Abdominal Surgery

Intensive Care Medicine - Balanced versus Unbalanced Crystalloids

Intensive Care Medicine - HFNO vs NIV for Pre-Oxygenation in Hypoxic ICU patients

Critical Care - Steroids in Early Sepsis-Associated ARDS

Am J Respir Crit Care Med - Helium / Oxygen in Exacerbations of COPD

Intensive Care Medicine - Intravascular Catheter Dressings

J Crit Care - Intensity of Feeding

ESICM 2016

NEJM - Levosimendan in Sepsis




JAMA - Intubation during Paediatric Cardiac Arrest

Therapeutic Hypothermia & Cardiac Arrest

JAMA - Steroids in Sepsis

Intensive Care Medicine - Fluid Resuscitation in Sepsis

Intensive Care Medicine - Nitric Oxide during Cardiopulmonary Bypass

Intensive Care Medicine - NAVA

Intensive Care Medicine - IV Iron for Anaemia

Intensive Care Medicine - Recovery Programme

Lancet - Early, Goal-Directed Mobilisation

Critical Care Medicine - Dopamine vs Adrenaline in Septic Shock

 Neurosurgery - 4th Brain Trauma Foundation TBI Guideline

NEJM - High Flow Nasal Oxygen for Preterm Infants

Crit Care Med - Stress Ulcer Prophylaxis

Liver International - Vasopressor Support for Cirrhosis & Septic Shock

NEJM - Decompressive Craniotomy

Am J Respir Crit Care Med - Sevoflurane for Sedation ARDS

Chinese Medical Journal - Evaluation of Coma after Cardiac Arrest

N Engl J Med - Factor Xa Inhibitor Related Bleeding

Lancet Respiratory Medicine - Sedation & Analgesia

JAMA Cardiology - Nonshockable Out-of-Hospital Cardiac Arrest

Shock - Hydrocortisone in Septic Shock

JAMA Internal Medicine - Sodium Selenite & Procalcitonin in Sepsis

Journal of Critical Care - Heparin for Pneumonia in Ventilated Patients

European Heart Journal - Acute Heart Failure Guideline

Clinical Infectious Diseases - HAP & VAP Guideline

Am J Respir & Crit Care Med - Burnout Syndrome in Critical Care Professionals

JAMA - Palliative Care-Led Meetings

Lancet - Platelet Transfusion in Haemorrhagic Stroke

JAMA - Timing of Renal Replacement Therapy in AKI

American Thoracic Society Meeting

New England Journal of Medicine:     Timing of Renal Replacement Therapy in AKI

JAMA:     Aspirin for the Prevention of ARDS

JAMA:     Helmet NIV for ARDS

American Journal of Kidney Disease:     Renal Replacement Therapy Dose

Journal of the American College of Cardiology:     Early Aldosterone Blockade in Acute MI

Resuscitation:     Video Laryngoscopy during CPR

Critical Care:     European Guideline on Bleeding & Coagulopathy post Trauma

JAMA:     Checklists

Resuscitation:     Hypercapnoea post Cardiac Arrest

NEJM:     Antiarrhythmics in Out-of-Hospital Cardiac Arrest

Critical Care:     Steroids for Refractory Shock post Cardiac Arrest

Intensive Care Medicine:     Probiotics for the Prevention of VAP

Brussel's International Symposium on Intensive Care & Emergency Medicine

JAMA:  Dexmedetomidine Sedation in ICU

JAMA: High-Flow Nasal Oxygen post Extubation

JAMA: Non-Invasive Ventilation post Extubation after Abdominal Surgery

JAMA: Secondary Infections post Sepsis

NEJM: Early TPN in Childern

Critical Care Medicine:  Fragility Index in Critical Care

Journal of Infection - UK Meningitis Guidelines

JAMA - Sepsis Definition

JAMA - Statins for AKI

JAMA - ARDS Epidemiology

Lancet Respiratory Medicine - Effect of Light on Delirium

Intensive Care Medicine - Blood Pressure Targets in Shock

NICE Trauma Guideline

JAMA - Acetazolamide for COPD

Intensive Care Medicine - Percutaneous Dilational Tracheostomy

Pediatric Crit Care Med - Aminophylline for Prevention of AKI

Blue Journal - End-of-Life Communication

JPEN J Parenter Enteral Nutr - Nutritional Support in the Critically Ill

Intensive Care Medicine - Continuous vs Intermittent Beta Lactam Infusion

Chest - Antithrombotic Therapy for VTE

Resuscitation - TTM post Cardiac Arrest

German Medical Society - Delirium, Analgesia & Sedation Guideline

Annals of Intensive Care - Renal Replacement Therapy Guideline

ANZICS - Acute Pain Management Scientific Evidence


Journal of Thrombosis and Haemostasis - Guideline on Antidotes for Direct Oral Anticoagulants

American Journal of Respiratory & Critical Care Medicine:     Physical Therapy for Respiratory Failure

NICE Guideline on Acute Heart Failure

NICE Guideline on IV Fluid Therapy in Young People

Journal of Trauma:  Western Trauma Guidelines

Critical Care Medicine:     SCCM Guideline on Ultrasound in Critical Care

Critical Care Medicine: SCCM Guideline on Organ Procurement

Critical Care Medicine:    SCCM Guideline on ICU Process & Structures

Lancet Infectious Diseases:     Body Surface Decolonization & UTIs

JAMA:     Transfusion in Anaemic Children with Elevated Lactate

Intensive Care Medicine:  Post-Resuscitation Care Guideline

American Heart Association:  ST-Elevation MI Guideline Update

American Heart Association:  Infective Endocarditis Guideline

2015 Cardiac Arrest Guidelines

  1. Part 1: Executive Summary: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015;132:S315-S367
  2. Part 2: Evidence Evaluation and Management of Conflicts of Interest: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015;132:S368-S382
  3. Part 3: Ethical Issues: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015;132:S383-S396
  4. Part 4: Systems of Care and Continuous Quality Improvement: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015;132:S397-S413
  5. Part 5: Adult Basic Life Support and Cardiopulmonary Resuscitation Quality: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015;132:S414-S435
  6. Part 6: Alternative Techniques and Ancillary Devices for Cardiopulmonary Resuscitation: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015;132:S436-S443
  7. Part 7: Adult Advanced Cardiovascular Life Support: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015;132:S444-S464
  8. Part 8: Post–Cardiac Arrest Care: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015;132:S465-S482
  9. Part 9: Acute Coronary Syndromes: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015;132:S483-S500
  10. Part 10: Special Circumstances of Resuscitation: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015;132:S501-S518
  11. Part 11: Pediatric Basic Life Support and Cardiopulmonary Resuscitation Quality: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015;132:S519-S525
  12. Part 12: Pediatric Advanced Life Support: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care
  13. Circulation 2015;132:S526-S542
  14. Part 13: Neonatal Resuscitation: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015;132:S543-S560
  15. Part 14: Education: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015;132:S561-S573

ESICM Hot Topics and New Trials

N Engl J Med:     Plasmalyte vs Saline

JAMA:     Paracetamol for Fever in Critically ill with Suspected Infection

Lancet:     Erythropoietin for Traumatic Brain Injury

N Engl J Med:     Hypothermia for Intracranial Hypertension in Traumatic Brain Injury

Am J Respir Crit Care Med:     Apnoeic Oxygenation

JAMA:     ICU Admission for Older Adults with Pneumonia

JAMA:     Do-Not-Resuscitate Status


NEJM:     CVC Insertion Site

Clinical Drug Investigation:  Esmolol for Sepsis

Lancet:     Methylprednisolone for Cardiopulmonary Bypass

Lancet:     Sigmoid Diverticulitis

Lancet:  CVC Line Infection Prevention

American Journal of Respiratory & Crit Care Med:     End-of-Life Care

Critical Care:     Laxative Therapy

Lancet:  Oxyenation Target in Bronchiolitis

Lancet:  Bubble CPAP for Paediatric Pneumonia

European Journal of Anesthesiology:     Pre-Oxygenation

Critical Care Medicine:     Vasopressors for Paediatric Septic Shock

Blue Journal:     Oxygenation Targets in Mechanically Ventilated Patients

Journal of Hepatology:     Plasma Exchange for Acute Liver Failure

Circulation:     ESC Guidelines on Pulmonary Hypertension | Pericardial Disease | Non-Persistent ST Elevation Coronary Syndromes | Infective Endocarditis

British Journal of Haematology:     Guideline on Admission for Haematology Cancer Patients

Journal of Trauma:  Early Surgery in Traumatic Brain Injury

Annals of Surgery:     Cryopreserved Packed Red Cells

NEJM / Lancet:     Idarucizumab for Dabigatran

Lancet:     Bioprosthetic Total Artificial Heart Heart

New England Journal of Medicine:     Hypothermia for Deceased Kidney Donor Graft

JAMA:     Bystander CPR

Blue Journal:     β-Lactam Infusion in Severe Sepsis

Perioperative Medicine:     Stroke Volume Variation

Critical Care Medicine:    Critical Care Interventions

Blue Journal:     Haemofiltration for Postcardiac Surgery Shock

Annals of Surgery:     Abdominal Vacuum Therapy post Laparotomy

Annals of Intensive Care:     Guideline on Cardiogenic Shock

Journal of Trauma:     Guideline on ED Thoracotomy

Critical Care Medicine:     Hypothermia for Paediatric Traumatic Brain Injury

Circulation:     Targeted Temperature Management

New England Journal of Medicine:     Out-of-Hospital CPR

New England Journal of Medicine:     Stroke Thrombolysis

New England Journal of Medicine:     Stroke Thrombectomy

Blue Journal:     Guideline on Requests for Inappropriate ICU Therapy

Blue Journal:     Guideline on Managing Conscientious Objections in ICM

Journal of Cardiac Failure:     Statement on Percutaneous Mechanical Circulatory Support

European Heart Journal:     Guideline on Acute Heart Failure

Stroke:     Guideline on Spontaneous Intracerebral Haemorrhage

Critical Care Medicine:     Talactoferrin for Sepsis

New England Journal of Medicine:     Intra-Abdominal Infection

American Thoracic Society Meeting 2015

New England Journal of Medicine:     Underfeeding

New England Journal of Medicine:     High Flow Nasal Oxygen

Journal of the American Medical Association:     High Flow Nasal Oxygen

Lancet:     Red Cell Transfusion in Upper GI Haemorrhage

 British Medical Journal:     MRSA Therapy

AJRCCM:     GUIDELINE - Conscientious Objections in ICU

Intensive Care Society:     Provision of Intensive Care Servces

Neurocritical Care:     Hemispheric Infarction

Neurocritical Care:     Devastating Brain Injury

Swiss Medical Weekly:     Ethics in ICU

New England Journal of Medicine:     Paediatric Therapeutic Hypothermia post Cardiac Arrest

New England Journal of Medicine:     Alcoholic Hepatitis

Intensive Care Medicine:     High Flow Nasal Cannulae Oxygen for Intubation

JAMA Internal Medicine:     Post ICU Rehabilitation

Intensive Care Medicine:     Polymyxin B Hemoperfusion

Chest:     Surfactant in ARDS

Intensive Care Medicine:    Early Rehabilitation

Critical Care Medicine:     Regional Citrate Anticoagulation for RRT

NEJM:     Age of Transfused Red Cells

NEJM:     ARDS Driving Pressure

JAMA:     Steroids for Community-Acquired Pneumonia

Acta Anaesthesiologica Scandinavica:     Fluid Resuscitation Guideline

NEJM:     Endovascular Stroke Therapy

Journal of Trauma:     EAST Guideline on Clearing the Cervical Spine in the Obtunded Patient

NEJM:     Stroke Neuroprotection

JAMA:     Trauma Transfusion Ratios


Lancet Respiratory Medicine:     Perioperative Goal-Directed Oxygen Delivery

JAMA:     Hypoxaemic Ischaemic Encephalopathy

New England Journal of Medicine:     Endovascular Stroke Therapy

New England Journal of Medicine:     Traumatic Brain Injury

Stroke:     Statins for Subarachnoid Haemorrhage

Lancet:     Red Cell Transfusion Triggers

 Lancet:     IV Fluid Therapy

Intensive Care Medicine:     Therapeutic Hypothermia for Cardiac Arrest

Intensive Care Medicine:    Balanced Crystalloid Solutions

Cell Transplantation:     Spinal Cord Regeneration

Resuscitation:     Refractory Cardiac Arrest

Journal of Clinical Epidemiology:     Fragility Index

ESICM Congress Studies

New England Journal of Medicine:     ARISE Study

The ARISE study Investigators completed a large, international, multi-centre, parallel group, randomized controlled trial, comparing early goal-directed therapy (n=796) with usual care (n=804) in 1600 patients presenting to the emergency department with early septic shock, and found:

  1. groups were similar at baseline
  2. no significant differences in
    • 90 day mortality
      • EGDT 18.6% vs UC 18.8%
      • absolute risk difference with EGDT vs UC, −0.3%; 95% CI -4.1 to 3.6; P = 0.90
    • survival time
    • mortality
      • ICU
        • 10.9 vs 12.9; RR 0.85, 95% CI 0.64 to 1.13; P=0.28
      • hospital
        • 14.5 vs 15.7; RR 0.92, 95% CI 0.73 to 1.17; 0.53
      • day 28 
        • 14.8 vs 15.9; RR 0.93 95% CI 0.73 to 1.17; P=0.53
    • duration of organ support
    • length of
      • ICU stay
        • 2.8 vs 2.8 days; p=0.81
      • hospital stay
        • 8.2 vs 8.5 days; p=0.89
  3. EGDT was associated with
    • greater fluid administration in the first 6 hours
      • 1964±1415 ml vs 1713±1401 ml
    • increased liklihood of receiving
      • vasopressors
        • 66.6% vs. 57.8%; P<0.001
      • red-cell transfusions
        • 13.6% vs. 7.0%; P<0.001
      • dobutamine
        • 15.4% vs. 2.6%; P<0.001

New England Journal of Medicine:     TRISS Study

Holst and colleagues completed a Scandanavian multicenter, randomized, parallel-group trial in 1,005 patients (998 analyzed) with shock and a haemoglobin concentration ≤ 9g/dL, comparing a red cell transfusion trigger of ≤ 7g/dL with ≤ 9g/dL and found

  1. both groups were similar at baseline (≤ 7 g/d vs <9 g/dL)
    • SOFA median 10 vs 10; SAPS II median 51 vs 52
  2. the more restrictive transfusion trigger was associated with
    • less units of transfused red cells (median/IQR)
      • 1 (0-3) vs 4 (2-4)
  3. there was no statistically significant difference in (≤ 7 g/d vs <9 g/dL)
    • 90 day mortality
      • 43% vs 45%; RR 0.94; 95% CI 0.78 to 1.09; P = 0.44
    • ischemic events 
      • 7.2% vs 8%, RR 0.90, 95% CI 0.58 to 1.39, P=0.64
    • severe adverse reactions
      • 0 vs 0.2%, P≈1.0
    • requiring life support
      • at day 5: 64.4% vs 62.2%, RR 1.04, 95% 0.93 to 1.14; P=0.47
      • at day 14: 36.8% vs 36.8%, RR 0.99, 95% 0.81 to 1.19; P=0.95
      • at day 28: 7.2% vs 8.0%, RR 0.90, 95% CI 0.58 to 1.39; P=0.64
    • alive without vasopressor or inotropic therapy (mean % of days)
      • 73% vs 75%; P=0.93
    • alive without mechanical ventilation (mean % of days)
      • 65% vs 67%; P=0.49
    • alive without renal-replacement therapy (mean % of days)
      • 85% vs 83%; P=0.54
    • alive and out of the hospital (mean % of days)
      • 30% vs 31%; P=0.89

Unpublished:     EPO ACR 02

Cariou and colleagues completed a French, multi-centre, parallel group, randomised controlled trial, comparing early, high-dose erythropoietin (40,000 IU immediately after ROSC and 12 hourly for 48 hours, n=234) with placebo (n=242) in 476 patients with return of spontaneous circulation after out-of-hospital cardiac arrest, and found:

  1. groups were similar at baseline
  2. there was no difference in
    • neurological recovery
    • cerebral performance category 1 (best outcome) - 32% each
    • mortality (missed the figure)
    • duration mechanical ventilation
      • Epo 5.6 days vs placebo 6.0 days; p=0.61
  3. erythropoietin was associated with increased rates of
    • thrombosis
      • 12.4% vs 5.8%; p=0.01
    • acute stent thrombosis
      • 8 (3.4%) vs 1 (0.4%); p=0.02

New England Journal of Medicine:     CALORIES

Journal of the American Medical Association:     SDD vs SOD

ESICM Congress Studies

Journal of the American Medical Association:     VITdAL-ICU Study

Amrein and colleagues performed a randomized double-blind, placebo-controlled, single-center study in 492 critically ill patients with vitamin D deficiency (≤20 ng/mL), comparing vitamin D3 administration (PO or NG, 540,000 IU followed by monthly maintenance doses of 90,000 IU for 5 months; n=249) with placebo (n=243), and found:

  1. 475 patients were included in the final analysis (vit D n=237; placebo n=238)
  2. there were no significant differences in (median / IQR)
    • length of hospital stay
      • vit D: 20.1 days [11.1-33.3] vs placebo 19.3 days [11.1-34.9]; P = 0.98
    • mortality
      • hospital
        • vit D 28.3% [95% CI 22.6%-34.5%] vs placebo 35.3% [95% CI 29.2%-41.7%]; HR 0.81 [95% CI 0.58-1.11]; P=0.18
      • 6-month
        • vit D 35.0% [95% CI 29.0%-41.5%] vs placebo 42.9% [95% CI 36.5%-49.4%]; HR 0.78 [95% CI 0.58-1.04]; P = 0.09
  3. in the most severe vitamin D deficiency subgroup (n = 200)
    • no significant differences in
      • length of hospital stay
        • vit D 20.1 days (12.9-39.1) vs placebo 19.0 days (11.6-33.8)
      • 6-month mortality
        • vit D 34.7% [95% CI 25.4%-45.0%] vs placebo 50.0% [95% CI 39.9%-60.1%]; HR 0.60 [95% CI 0.39-0.93], P for interaction = 0.12
    • vit D was associated with significantly lower
      • hospital mortality
        • 28.6% [95% CI 19.9%-38.6%] vs 46.1% [95% CI 36.2%-56.2%]; HR 0.56 [95% CI 0.35-0.90], P for interaction = 0.04

Unpublished:     FLORALI Study

In 310 patients with acute hypoxaemic respiratory failure (PaO2 /FiO2 < 300 mmHg), standard oxygen therapy (n=94) was compared with high flow nasal oxygen (n=106) and with a combination of noninvasive ventilation (minimum 8 hours per day) and HFNO (n=110). The authors found:

  1. most patients had either community-acquired pneumonia (≈60%) or hospital-acquired pneumonia (≈10%)
  2. 77% had a PaO2 /FiO2 < 200 mmHg
  3. no difference in the requirement for invasive mechanical ventilation (1° outcome)
    • SOT 46.8 % vs HFNO 37.7% vs NIV/HFNO 50%; p=0.17
      • reduced requirement for invasive mechanical ventilation in those with a PaO2 /FiO2 < 200 mmHg (n=238)
      • SOT 52.7 % vs HFNO 34.9% vs NIV/HFNO 58%; p=0.009
  4. reduced 
    • ICU mortality
      • SOT 19.1 % vs HFNO 11.3 % vs NIV/HFNO 24.5 %; p<0.05
    • 90 day mortality
      • SOT 23.4 % vs HFNO 12.3 % vs NIV/HFNO 28.2 %; p<0.05

New England Journal of Medicine:  Ebola Virus Disease

Critical Care Medicine:  Fatty Acid Supplementation

Anesthesiology:  Erythropoietin & Acute Kidney Injury

European Heart Journal:  STEMI

European Heart Journal:  Guidelines

European Journal of Anaesthesiology:  Cardiovascular Assessment & Management for Non-Cardiac Surgery

Canadian Medical Association Journal:  Melatonin for Delirium

ESC Congress Studies

ESC Congress Studies

European Heart Journal:     ESC Guidelines

Infection Control and Hospital Epidemiology:     Healthcare-Associated Infection Guidelines

Journal of the American Medical Association:     Immunonutrition

Abstract:  van Zanten. High-Protein Enteral Nutrition Enriched With Immune-Modulating Nutrients vs Standard High-Protein Enteral Nutrition and Nosocomial Infections in the ICU. A Randomized Clinical Trial (MetaPlus study). JAMA 2014;312(5):514-524

British Medical Journal:     Albumin in Sepsis

Full Text:  Patel. Randomised trials of human albumin for adults with sepsis: systematic review and meta-analysis with trial sequential analysis of all-cause mortality. BMJ 2014;349:g4561

Annals of Internal Medicine:     Fluid Resuscitation in Sepsis

Abstract:  Rochwerg. Fluid Resuscitation in Sepsis: A Systematic Review and Network Meta-analysis. Ann Intern Med 2014;epublished July 22nd

Anesthesia & Analgesia:     Perioperative Goal-Directed Therapy

Pestaña and colleagues completed a pragmatic, multi-centre study in 142 patients undergoing general surgery, comparing a noninvasive cardiac output monitor guided hemodynamic protocol, including fluid administration and vasoactive drugs, with standard practice, and found:

  • the interventional protocol was associated with
    • an increase in the number of
      • colloid boluses (2.4 ± 1.8 vs 1.3 ± 1.4; P < 0.001)
      • packed red blood cell units (0.6 ± 1.3 vs 0.2 ± 0.6; P = 0.019)
      • dobutamine use (p < 0.001)
        • intraoperatively: 25% vs 1.4%
        • postoperatively: 19.4% vs 0%
    • reduced
      • reoperations (5.6% vs 15.7%; P = 0.049)
    • no statistically significant differences in
      • overall fluid administration
      • overall complications (40% vs 41%)
        • relative risk 0.99; 95% CI 0.67 to 1.44; P = 0.397
      • length of stay (11.5 [8-15] vs 10.5 [8-16]; P = 0.874)
      • time to first flatus (62 hours [40-76] vs 72 hours [48-96]; P = 0.180)
      • wound infection (7 vs 14; P = 0.085)
      • anastomotic leaks (2 vs 5; P = 0.23)
      • mortality (4.2% vs 5.7%; P = 0.67)

Conclusion: The use of a perioperative goal-directed haemodynamic protocol in major abdominal surgery was not associated with reductions in overall complications, length of hospital stay, or mortality.

Abstract:  Pestaña. Perioperative Goal-Directed Hemodynamic Optimization Using Noninvasive Cardiac Output Monitoring in Major Abdominal Surgery: A Prospective, Randomized, Multicenter, Pragmatic Trial: POEMAS Study (PeriOperative goal-directed thErapy in Major Abdominal Surgery). Anesth Analg 2014;epublished July 9th

JAMA: Red Cell Management in Traumatic Brain Injury

Robertson and colleagues, using a factorial design, compared intravenous erythropoietin (500 IU/kg per dose, n=102) with saline (n=98), plus red cell transfusion at a threshold of either 7 g/dL (n=99) or 10 g/dL (n=101), on Glasgow Outcome Scale score at 6 months postinjury, in 200 patients within 6 hours of closed head injury and unable to follow commands. Erythropoietin or placebo was initially dosed daily for 3 days and then weekly for 2  weeks (group 1, n = 74). The protocol was subsequently amended to (I think, it's remarkably poorly described) a single erythropoietin dose, possibly followed by further doses at 1 and 2 weeks if the patient was still in ICU (n=126). The authors found:

  1. no interaction between erythropoietin and hemoglobin transfusion threshold
  2. no statistical improvement on favorable outcome rate (dichotomized as favorable (good recovery and moderate disability) or unfavorable (severe disability, vegetative, or dead))
    • between placebo and erythropoietin
      • placebo: 38.2%; 95% CI 28.1% to 49.1%
      • erythropoietin
        • first dosing regimen:  48.6%; 95% CI 31.4% to 66.0%, P =0.13
        • second dosing regimen: 29.8%; 95% CI 18.4% to 43.4%; P  < 0.001
    • between haemoglobin transfusion thresholds
      • 7 g/dL:  42.5%
      • 10 g/dL: 33.0%
        • 95% CI for the difference −0.06 to 0.25, P = 0.28
  3. the 10 g/dL transfusion threshold was associated with a
    • higher incidence of thromboembolic events (21.8% vs 8.1%; odds ratio 0.32, 95% CI 0.12 to 0.79; P = 0.009)

Conclusion: In a two centre, factorial, randomized controlled trial, in patients with closed head injury, neither erythropoietin administration nor red blood cell transfusion maintaining a haemoglobin level of ≥10 g/dL versus ≥ 7 g/dL, were statistically associated with improved outcomes, with the higher haemoglobin level associated with more thrombotic events.

Abstract:  Robertson. Effect of Erythropoietin and Transfusion Threshold on Neurological Recovery After Traumatic Brain Injury:  A Randomized Clinical Trial. JAMA 2014;312(1):36 

New Engl J Med:  PEEP in General Anaesthesia

The PROVE Network Investigators compared high PEEP (median 12 cmH20) plus recruitment maneuvres (n=447) with low PEEP (median 2 cmH20) without recruitment manuevres (n=453) in 900 patients undergoing open abdominal surgery, ventilated with 8 ml/kg and at high risk for postoperative pulmonary complications, and found no difference in post-operative complications (high PEEP 40% vs low PEEP 39%, RR1·01; 95% CI 0·86 to1·20; p=0·86), but increased hypotension with higher PEEP, requiring more vasopressor therapy.

Abstract:  The PROVE Network Investigators. High versus low positive end-expiratory pressure during general anaesthesia for open abdominal surgery (PROVHILO trial): a multicentre randomised controlled trial. Lancet 2014;epubished May 30th

New Engl J Med:  Long-Acting Gram Positive Antibacterial Therapy

Boucher et al pooled two identically designed, industry funded, noninferiority trials, and found once-weekly IV dalbavancin (a long-acting lipoglycopeptide antibiotic active against gram positive bacteria, n=659) was non-inferior to twice-daily IV vancomycin followed by oral linezolid (n=653) for the treatment of acute bacterial skin and skin-structure infection, with no difference in early clinical response indicating treatment success (79.7% vs 79.8%, respectively; weighted difference, −0.1%; 95% CI−4.5 to 4.2%), or side effects. Individual study analyses yielded similar results, as did pooled analysis of clinical status at end of therapy.

Abstract:  Boucher. Once-Weekly Dalbavancin versus Daily Conventional Therapy for Skin Infection (DISCOVER 1 & 2 studies).  N Engl J Med 2014;370:2169-2179

New Engl J Med:  Long-Acting Gram Positive Antibacterial Therapy

Corey and colleagues found a single dose of IV oritavancin (a long-acting lipoglycopeptide with bactericidal activity against gram-positive bacteria, n=475) was non-inferior to a regimen of twice daily IV vancomycin for 7 to 10 days (n=479) in 954 adults with acute bacterial skin and skin-structure infections, for three main outcomes:

  • spreading or reduction in lesion size, absence of fever, and no need for administration of a rescue antibiotic after 48 to 72 hours (82.3% vs 78.9%, respectively;  95% CI for difference −1.6 to 8.4%)
  • clinical cure 7 to 14 days after the end of treatment, as determined by a study investigator (79.6% vs 80.0%, 95% CI for difference −5.5 to 4.7%)
  • reduction in lesion size of 20% or more after 48 to 72 hours (86.9% vs 82.9%, 95% CI for difference −0.5 to 8.6%)

Abstract:  Corey. Single-Dose Oritavancin in the Treatment of Acute Bacterial Skin Infections (SOLO I study). N Engl J Med 2014;370:2180-2190 

Brar and colleagues completed a randomised, parallel-group, comparator-controlled, single-blind phase 3 trial, comparing a left ventricular end-diastolic pressure-guided fluid administration protocol with a standard fluid administration protocol in 396 adults undergoing cardiac catheterisation with an estimated glomerular filtration rate of 60 mL/min/1·73 m2 or less, and one or more of several risk factors, and found:

  1. the new fluid protocol was associated with
    • a reduced incidence of contrast-induced acute kidney injury 
    • 6·7% vs. 16·3%; RR 0·41, 95% CI 0·22 to 0·79; p=0·005
  2. hydration treatment was terminated prematurely because of shortness of breath in three patients in each group

Abstract:  Brar. Haemodynamic-guided fluid administration for the prevention of contrast-induced acute kidney injury: the POSEIDON randomised controlled trial. Lancet 2014;383(9931):1814-1823

Kirkpatrick and colleagues completed an international, multicentre, randomised, double-blind trial, comparing simvastatin 40 mg (n=391) with placebo (n=412) once a day for up to 21 days, in 803 adults within 96 hours of  subarachnoid haemorrhage, and found:

  1. no between-group difference in
    • incidence of favourable modified Rankin Scale (mRS) score, obtained by questionnaire at 6 months (1° outcome)
      • simvastatin 271 vs placebo 289
      • OR 0·97, 95% CI 0·75 to 1·25; p=0·803
    • mortality at 6 months
      • simvastatin 10% (n=37) vs placebo 9% (n=35); log-rank p=0·592
    • serious adverse events
      • 18% vs 18%

Abstract:  Kirkpatrick. Simvastatin in aneurysmal subarachnoid haemorrhage (STASH): a multicentre randomised phase 3 trial. Lancet Neurology 2014;epublished May 16th

Pearse and colleagues completed a pragmatic, multicenter, randomized, observer-blinded trial of 734 high-risk UK patients aged 50 years or older, undergoing major gastrointestinal surgery, comparing the effectiveness of a perioperative, cardiac output–guided hemodynamic therapy algorithm consisting of IV fluid and dopexamine infusion during and 6 hours following surgery (n=368) with standard care (n=366), as well as a systematic review and meta analysis evaluating perioperative goal directed care, and found:

  1. in the randomized controlled trial
    • groups were similar at baseline
    • nonadherence was < 10% in each group
    • the hemodynamic therapy algorithm was associated with
      • a trend towards a reduction in composite outcome of 30-day complications and mortality (1° outcome)
        • 36.6% vs 43.4% (RR 0.84, 95% CI 0.71 to 1.01; absolute risk reduction 6.8%, 95% CI −0.3% to 13.9%; P = 0.07)
      • no significant difference between groups for any secondary outcomes.
        • morbidity on day 7
          • 66.2% vs 67.9%; RR 0.97, 95% CI 0.87 to 1.09; P=0.72
        • infectious complications at day 30
          • 23.8% vs 29.7%; RR 0.80, 95% CI 0.63 to 1.02; P=0.08
        • critical care–free days at day 30
          • 27 vs 28; P=0.98
        • all-cause mortality at 30 days following surgery
          • 3.3% vs 3.0%; RR 1.08, 95% CI 0.48 to 2.43; P>0.99
        • all-cause mortality at 180 days following surgery
          • 7.7% vs 11.6%; RR 0.66, 95% CI 0.42 to 1.05; P=0.08
        • duration of acute hospital length of stay
          • 10 vs 11; P=0.05
        • a trend for increased cardiovascular serious adverse events within 24 hours (1.4% (n=5) vs 0) (P = 0.06)
  2. in the meta analysis (38 studies, n=6,595)
    • perioperative goal-directed therapy was associated with
      • fewer complications
        • 31.5% vs 41.6%; RR 0.77, 95% CI 0.71 to 0.83
      • nonsignificant reductions in mortality
        • hospital / 28-day / 30-day 
          • 4.9% vs 6.5%; RR 0.82, 95% CI 0.67 to 1.01
        • at longest follow-up
          • 8.3% vs 10.3%; RR 0.86, 95% CI 0.74 to 1.00

Full Text:  Pearse. Effect of a Perioperative, Cardiac Output–Guided Hemodynamic Therapy Algorithm on Outcomes Following Major Gastrointestinal SurgeryA Randomized Clinical Trial and Systematic Review (OPTIMISE). JAMA 2014;epublished May 19th

Liu and colleagues quantified the contribution of sepsis to mortality in 2 complementary inpatient cohorts from Kaiser Permanente Northern California (n=482,828) and the Healthcare Cost and Utilization Project Nationwide Inpatient Sample (n=6,500,000), and found:

  1. the number of sepsis hospitalizations were
    • KPNC cohort
      • 55,008 explicit (11.4% of total; 95% CI 11.3% to 11.5%) 
      • 80,678 implicit (16.7%; 95% CI 16.6% to 16.8%)
    • NIS cohort
      • 280 663 explicit  (4.3%; 95% CI  4.3% to 4.3%)
      • 717,718 implicit (10.9%; 95% CI 10.9% to 11.0%)
  2. the numbers of inpatients dying with a diagnosis of sepsis were
    • KPNC cohort
      • of 14, 206 inpatient deaths
        • explicit sepsis: 36.9% (95% CI 36.1% to 37.7%)
        • implicit sepsis: 55.9% (95% CI 55.1% to 56.7%)
        • nearly all present on admission. 
    • NIS cohort
      • of 143,312 deaths
        • explicit sepsis: 34.7% (95% CI 34.4% to 34.9%) 
        • implicit sepsis: 52.0% (95% CI 51.7% to 52.2%)
  3. In the 2012 linked KPNC subset
    • patients with sepsis meeting criteria for EGDT (n = 2,536)
      • comprised 32.6% (95% CI 30.4% to 34.7%) of sepsis deaths
    • patients with sepsis, normal blood pressure, and measured lactate levels of less than 4 mmol/L (n = 15,095)
      • comprised 55.9% (95% CI 53.6% to 58.1%) of sepsis deaths

Full Text:  Liu.  Hospital Deaths in Patients With Sepsis From 2 Independent Cohorts. JAMA 2014;epublished May 18th

The ARDSnet group performed a blinded, multicenter, randomized, controlled trial comparing rosuvastatin with placebo in 745 critically ill, mechanically ventilated patients with sepsis-associated ARDS, and found:

  1. the study was stopped early for futility
    • 745 out of a planned 1000 patients were recruited
  2. both groups were similar for
    • demographics
    • physiology
  3. there were no significant differences in
    • 60-day in-hospital mortality
      • rosuvastatin: 28.5% vs placebo 24.9% (P=0.21) 
    • ventilator-free days (mean ±SD)
      • rosuvastatin: 15.1±10.8 vs placebo 15.1±11.0 (P=0.96)
    • serum creatine kinase levels above 10 times the upper limit of normal
  4. rosuvastatin was associated with fewer days free of
    • renal failure to day 14
      • 10.1±5.3 vs. 11.0±4.7 (P=0.01)
    • hepatic failure to day 14
      • 10.8±5.0 vs. 11.8±4.3 (P=0.003)

Full Text:  The National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. Rosuvastatin for Sepsis-Associated Acute Respiratory Distress Syndrome (SAILS). New Engl J Med 2014;epublished May 18th

April 2014

Vincent et al performed an international (84 countries, 730 centres, 10,069 patients) 10 day audit assessing ICU mortality, and found:

  1. regional recruitment was
    • Europe (5445 patients; 54·1%)
    • Asia (1928; 19·2%)
    • the Americas (1723; 17·1%)
    • Oceania (439; 4·4%)
    • the Middle East (393; 3·9%)
    • Africa (141; 1·4%)
  2. 2973 patients (29·5%) had sepsis on admission or during the ICU stay
  3. mortality rates
    • ICU
      • overall 16·2% (95% CI 15·5 to 16·9) 
      • in sepsis 25·8% (95% CI 24·2 to 27·4) 
    • hospital
      • overall 22·4% (95% CI 21·6 to 23·2) 
      • in patients with sepsis 35·3% (95% CI 33·5 to 37·1) 
  4. using a multilevel analysis, the unconditional model suggested significant variation in the individual risk of in-hospital death
    • between-country (var=0·19, p=0·002)
    • between-hospital (var=0·43, p<0·0001) 
  5. a stepwise increase in the adjusted risk of in-hospital death according to decrease in global national income

Kumar and colleagues performed a prospective, open-label randomized controlled trial, comparing cerebral perfusion pressure-targeted therapy (n=55) with intracranial pressure-targeted therapy (n=55) in 110 neurologically impaired critically ill children with raised intracranial pressure due to acute CNS infection. CPP was mainatined at ≥ 60 mm Hg, using normal saline and dopamine, with noradrenaline if needed; ICP was maintained < 20 mm Hg with osmotherapy while ensuring maintanence of normal blood pressure. The authors found:

  1. intracranial pressure-targeted therapy was associated with:
    • increased 90-day mortality 
      • 38.2% vs 18.2%; relative risk = 2.1; 95% CI 1.09 to 4.04; p = 0.020
  2. cerebral perfusion pressure-targeted therapy was associated with (median/IQR):
    • decreased
      • duration
        • PICU stay (13 d [10.8 to 15.2 d] vs 18 d [14.5 to 21.5 d], p = 0.002) 
        • mechanical ventilation (7.5 d [5.4 to 9.6 d] vs 11.5 d [9.5 to 13.5 d], p = 0.003)
      • prevalence of
        • hearing deficit (8.9% vs 37.1%; RR 0.69; 95% CI 0.53 to 0.90; p = 0.005)
        • neurodisability at
          • discharge from PICU (53.3% vs 82.9%; RR 0.37, 95% CI 0.17 to 0.81; p = 0.005) 
          • 90 days after discharge (37.8% vs 70.6%; RR 0.47, 95% CI 0.27 to 0.83; p = 0.004)
    • increased
      • modified Glasgow Coma Scale score at 72 hours (10 [8-11] vs 7 [4-9], p < 0.001)

Meyer and colleaguese compared tenecteplase plus heparin with placebo plus heparin in 1,006 normotensive patients with intermediate-risk pulmonary embolism, identified by right ventricular dysfunction (on echo or CT) and myocardial injury (positive troponin I or T), and found:

  1. tenecteplase plus heparin was associated with
    • reduced rate of death or haemodynamic decompensation (1° outcome)
      • 2.6% (13/506) versus 5.6% (28/499) 
      • odds ratio 0.44; 95% CI 0.23 to 0.87; P=0.02
    • increased
      • extracranial bleeding
        • 6.3% versus 1.2%  (P<0.001)
      • stroke
        • 2.4% versus 0.2%  (P=0.003)
        • hemorrhagic stroke - 10 patients versus 1 patient
  2. no difference in death by
    • day 7
      • tenecteplase plus heparin group: 1.2% versus heparin group 1.8% (P=0.42)
    • day 30
      • tenecteplase plus heparin group: 2.4% versus heparin group 3.2% (P=0.42)

Pitt and colleagues compared spironolactone (15 to 45 mg daily) with placebo in 3,445 patients with symptomatic heart failure and preserved left ventricular ejection fraction, and found over a median 3.3 year follow up:

  1. no difference in a composite of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure (1° outcome)
    • spironolactone 18.6% versus placebo 20.4%
    • hazard ratio 0.89; 95% CI 0.77 to 1.04; P=0.14
      • of the 1° outcome components, only hospitalization for heart failure had a significantly lower incidence in the spironolactone group
        • 12.0% versus 14.2%; HR 0.83, 95% CI 0.69 to 0.99, P=0.04
  2. spironolactone therapy was associated with
    • higher rate of hyperkalemia
      • 18.7% vs. 9.1%
    • a lower rate of hypokalemia
      • 16.2% vs. 22.9%
    • doubling of serum creatinine
      • 10.2% vs. 7.0%
  3. no significant differences in the
    • incidence of serious adverse events
    • serum creatinine level of 265 μmol/l (3.0 mg/dl) or higher
    • dialysis

Lilly investigated assessed the optimal method of managing increased risk for venous thrmboembolism based on 294,896 episodes of critical illness in 271 American adult intensive care units, and found:

  1. after adjustment for propensity to receive VTE prophylaxis, APACHE IV scores and management with mechanical ventilation, prophylactic anticoagulation was the only intervention associated with a lower risk of death compared with those not provided VTE prophylaxis
    • ICU mortality
      • hazard ratio 0.81, 95% CI 0.79 to 0.84, p<.0001
    • hospital mortality
      • hazard ratio 0.84, 95% CI 0.82 to 0.86, p<.0001
  2. mechanical devices, in comparison with no VTE prophylaxis, were not associated with a reduced mortality risk
  3. in a study of 87,107 pairs of patients matched for propensity to receive VTE prophylaxis
    • prophylactic anticoagulation was associated with a lower risk of death than those receiving only mechanical device prophylaxis
      • ICU sub-hazard ratio
        • 0.82, 95% CI 0.78 to 0.85; p < 0.001
      • hospital sub-hazard ratio
        • 0.82, 95% CI 0.79 to 0.85; p < 0.001

Jackson and colleagues followed up 821 critically ill patients with respiratory failure or shock in a prospective, multicentre cohort study, examining psychological and functional outcomes, and found:

  1. baseline data
    • median age of 61 years (IQR 51—71)
    • assessment post discharge
      • 448 patients at 3 months 
      • 382 patients at 12 months
  2. at least mild depression was present in
    • 37% at 3 months
    • 33% at 12 months
      • this depression was mainly due to somatic rather than cognitive—affective symptoms
  3. depressive symptoms were common among individuals without a history of depression
    • 30% at 3 months
    • 29% at 12 months
  4. post-traumatic distress disorder was present in
    • 7% at 3 and 12 months
  5. disabilities in
    • basic activities of daily living
      • 32% at 3 months
      • 27% at 12 months
    • instrumental activities of daily living
      • 26% at 3 months
      • 23% at 12 months

New England Journal of Medicine:     Perioperative Aspirin & Clonidine

Devereaux and colleagues performed an international, multicentre, blinded, randomized, controlled, 2-by-2 factorial trial permitting separate evaluation of low-dose clonidine versus placebo and low-dose aspirin versus placebo in 10,010 patients with, or at risk for, atherosclerotic disease who were undergoing noncardiac surgery.

In the aspirin arm, patients were statified by those already receiving aspirin (continuation stratum, n=4382) or not (initiation stratum, n=5628), to the perioperative administration of aspirin or placebo. Patients started taking aspirin (at a dose of 200 mg) or placebo just before surgery and continued it daily (at a dose of 100 mg) for 30 days in the initiation stratum and for 7 days in the continuation stratum, after which patients resumed their regular aspirin regimen. The authors found:

  1. no difference in the primary endpoint, a composite of death or nonfatal myocardial infarction at 30 days
    • aspirin group: 7.0% (351/4998) versus placebo group: 7.1% (355/5012)
    • hazard ratio in the aspirin group 0.99, 95% CI 0.86 to 1.15; P=0.92
  2. increased major bleeding with aspirin
    • 4.6% vs 3.8%, hazard ratio 1.23; 95% CI 1.01 to 1.49; P=0.04
  3. no differences in 1° or 2° outcomes between aspirin strata


In the clonidine arm, Deveraux compared low-dose clonidine (200 μg per day, commenced just before surgery and until 72 hours post surgery) with placebo, and found:

  1. no difference in
    • the primary endpoint, a composite of death or nonfatal myocardial infarction at 30 days
      • clonidine: n=367 vs placebo: n=339
      • hazard ratio with clonidine 1.08, 95% CI 0.93 to 1.26; p=0.29
  2. clonidine was associated with increased incidence of
    • myocardial infarction
      • clonidine 6.6% vs placebo 5.9%
      • hazard ratio with clonidine 1.11, 95% CI 0.95 to 1.30; P=0.18
    • clinically important hypotension
      • 47.6% vs 37.1%
      • hazard ratio with clonidine 1.32; 95% CI 1.24 to 1.40; P<0.001
    • nonfatal cardiac arrest
      • 0.3% (n=16) 0.1% (n=5)
      • hazard ratio 3.20; 95% CI 1.17 to 8.73; P=0.02

March 2014

New England Journal of Medicine:     Stroke Hemicraniectomy

PLoS One:     Acute Respiratory Distress Syndrome

European Heart Journal:     Myocardial Infarction

New England Journal of Medicine:     Septic Shock

The ProCESS investigators completed an American multi-centre, randomized controlled trial in 1,341 patients with early septic shock, comparing three management strategies:

  1. protocol-based early goal-directed therapy (n=439, based on the Rivers GDT protocol)
  2. protocol-based standard therapy (not requiring the placement of a central venous catheter, administration of inotropes, or blood transfusions, n=446)
  3. usual care (n=456)

and found:

  1. significant inter-group differences with respect to the monitoring of central venous pressure and oxygen and the use of intravenous fluids, vasopressors, inotropes, and blood transfusions.
  2. 60 day mortality rates:
    • protocol-based EGDT group: 21.0%
    • protocol-based standard-therapy group 18.2%
    • usual-care group 18.9%
      • relative risk with protocol-based therapy vs. usual care, 1.04; 95% CI 0.82 to 1.31; P=0.83
      • relative risk with protocol-based EGDT vs. protocol-based standard therapy, 1.15; 95% CI 0.88 to 1.51; P=0.31
  3. There were no significant differences in
    • 90-day mortality
    • 1-year mortality
    • need for organ support

New England Journal of Medicine:     Septic Shock

Asfar and colleagues completed a multicenter, randomized, open-label trial in 776 patients with septic shock comparing resuscitation with a mean arterial pressure target of 80 to 85 mm Hg (high target group) with 65 to 70 mmHg (low target group), and found:

  1. no significant difference in
    • 28 day mortality
      • high target group 36.6% versus low target group 34.0%
        • hazard ratio in the high target group 1.07, 95% CI 0.84 to 1.38; p=0.57
    • 90 day mortality
      • high target group 43.8% versus low target group 42.3%
        • hazard ratio in the high-target group 1.04, 95% CI 0.83 to 1.30; p=0.74
    • serious adverse events
      • high target group 19.1% versus low target group 17.8%; p=0.64
    • an increased incidence of atrial fibrillation with high-target therapy

New England Journal of Medicine:     Severe Sepsis

Caironi and colleagues completed a multicenter, randomized, controlled, open-label trial in 1,818 patients with severe sepsis, comparing 20% albumin and crystalloid solution (targeting a serum albumin level of 30 g/L), with crystalloid solution alone, and found:

  1. no difference in
    • 28 day mortality (primary outcome)
      • albumin group 31.8% versus crystalloid group 32.0%
        • relative risk in the albumin group, 1.00; 95% CI 0.87 to 1.14; P=0.94
    • 90 day mortality
      • albumin group 41.1% versus crystalloid group 43.6%
        • relative risk 0.94; 95% CI 0.85 to 1.05; P=0.29
  2. no significant differences in other secondary outcomes
    • organ dysfunction:
      • number of patients
      • degree of dysfunction
    • length of stay
      • ICU 
      • hospital
  3. during the first 7 days, albumin therapy was associated with
    • higher mean arterial pressure (P=0.03)
    • lower net fluid balance (P<0.001)
  4. no significant difference in total daily administered fluid  (P=0.10)

Journal of the American Medical Association:     Severe Sepsis

Kaukonen et al performed a retrospective, observational study from 2000 to 2012, in 101,064 patients with severe sepsis in Australia and New Zealand, and found:

  1. a decrease in absolute mortality:
    • from 35.0% in 2000 (95% CI  33.2% to 36.8%) to 18.4% in 2012 (95% CI 17.8% to 19.0%), P  < 0.001
  2. overall mortality decrease of 16.7% (95% CI 14.8% to 18.6%)
  3. an annual rate of absolute decrease of 1.3%
    • relative risk reduction of 47.5% (95% CI  44.1% to 50.8%)
  4. adjusted mortality decreased throughout the study period
    • odds ratio 0.49 (95% CI 0.46 to 0.52) in 2012, using the year 2000 as the reference (P < 0.001)
  5. no difference in annual mortality decline between patients with severe sepsis and those with all other diagnoses
    • OR 0.94 (95% CI 0.94 to 0.95) vs 0.94 (95% CI  0.94 to 0.94) P = 0.37
  6. a greater annual inc