Hot Articles

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


Critical Care Medicine - Transfusion in Critically Ill Oncology Patients

J Trauma - Damage Control Resuscitation Guideline

J Crit Care - Tracheostomy Guideline

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 increase in rates of discharge to home in patients with severe sepsis compared with all other diagnoses
    • OR  1.03 (95% CI 1.02 to 1.03) vs 1.01 (95% CI 1.01 to 1.01) P <0.001
  7. a smaller annual increase in the rate of patients discharged to rehabilitation facilities in patients with severe sepsis compared with all other diagnoses
    • OR 1.08 (95% CI 1.07 to 1.09) vs 1.09 (95% CI 1.09 to 1.10) P < 0.001
  8. in the absence of comorbidities and older age, mortality was less than 5%

Resuscitation:     Mechanical CPR

Wik and colleagues performed a multi-centre, unblinded, randomized controlled trial in 4,753 patients (11% met post enrollment exclusion criteria) with out-of-hospital cardiac arrest, comparing integrated automated load distributing band CPR (iA-CPR, n=2,099) with high-quality manual CPR (M-CPR, n=2,132), and found:

  1. no difference in primary outcome, survival to hospital discharge
    • adjusted odds ratio for iA-CPR compared to M-CPR: 1.06, 95% CI 0.83 to 1.37
    • demonstrating therapeutic equivalence
  2. for iA-CPR compared to M-CPR
    • sustained ROSC (emergency department admittance)
      • 28.6% vs 32.3%
    • 24 hour survival
      • 21.8% vs 25.0%
    • hospital discharge
      • 9.4% vs 11.0%
  3. 20 minutes CPR fraction
    • iA-CPR 80.4% vs M-CPR: 80.2%

Nephrology Dialysis Transplantation:     Hyponatraemia Guideline

JAMA Psychiatry:     Delirium

Hatta and colleagues completed a multicenter, rater-blinded, randomized placebo-controlled trial, evaluating ramelteon, a melatonin agonist, for the prevention of delirium, in 67 patients aged 65 to 89 years old, and found:

  1. ramelteon was associated with
    • a lower incidence of delirium (3% vs 32%; RR 0.09, 95% CI 0.01 to 0.069; p=0.003)
      • including controlling for risk factors (OR 0.07, 95% CI 0.008 to 0.54; p=0.01)
    • a longer time to the development of delirium (6.94 days vs 5.74)
    • a lower frequency of delirium (log rank test: χ2 = 9.83; p = 0.002)

Abstract:  Hatta. Preventive Effects of Ramelteon on Delirium. A Randomized Placebo-Controlled Trial. JAMA Psychiatry 2014;epublished February 19th 

Anesthesia & Analgesia:     Cricoid Pressure

Zeidan and colleagues investigated the efficacy of cricoid pressure (30 N) in 79 nonobese ASA I - II patients undergoing general anaesthesia with paralysis, using a glidoscope to visualise whether blinded nasogastric tube (both sizes 12 and 20 F) insetion into the oesophagus was successful both in the presence and absence of cricoid pressure, and found:

  1. the study was stopped after the recruitment of 79 patients
  2. success at NGT placement
    • in the presence of cricoid pressure - 0%
    • in the absence of cricoid pressure - 100%
  3. oesophageal patency was observed
    • in the presence of cricoid pressure - 0%
    • in the absence of cricoid pressure - 100%
  4. cricoid pressure did not change the position of the oesophageal entrance, relative to the glottis, which was
    • left lateral position: 57% (95% CI 45%–68%)
    • midline: 32% (95% CI 22%–43%), and in a
    • right lateral position: 11% (95% CI 5%–21%)

Abstract:  Zeidan. The Effectiveness of Cricoid Pressure for Occluding the Esophageal Entrance in Anesthetized and Paralyzed Patients: An Experimental and Observational Glidescope Study. Anesth Analg 2014;118(3):580–586

Critical Care Medicine:     Vasopressin in Septic Shock

Gordon and colleagues undertook a multi-centre, open-label, randomized controlled pilot trial, in 61 patients with septic shock, evaluating the addition of IV hydrocortisone (50 mg 6 hourly, n=31) or placebo (n=30) to a vasopressin infusion (titrated up to 0.06 U/min), examining for an interaction between vasopressin and corticosteroids in septic shock, and found:

  1. hydrocortisone therapy was associated with a
    • shorter duration of vasopressin therapy (difference 3.1 d; 95% CI 1.1 to 5.1)
    • lower total dose of vasopressin (ratio 0.47; 95% CI 0.32 to 0.71)
  2. there was no difference in
    • plasma vasopressin levels (hydrocortisone group +64 pmol/L difference at 6- to 12-hour time point; 95% CI -32 to 160 pmol/L)
    • 28 day mortality rate (23% both groups)
    • organ failure
  3. vasopressin use was well tolerated 

Abstract:  Gordon. The Interaction of Vasopressin and Corticosteroids in Septic Shock: A Pilot Randomized Controlled Trial. Crit Care Med 2014;2014 February 19th

JAMA Internal Medicine:     Stress Ulcer Prophylaxis

Wang and colleagues completed a large pharmacoepidemiological cohort study (71 hospitals, n=35,312) comparing histamine-2 receptor antagonists (n=13 439, 38.1%) with proton pump inhibitors (21 873, 61.9%) in adult patients requiring mechanical ventilation for ≥ 24 hours , and found:

  1. histamine-2 receptor antagonists were associated with less
    • gastrointestinal hemorrhage (2.1% vs 5.9%; P < 0.001)
    • pneumonia (27% vs 38.6%; P < 0.001)
    • Clostridium difficile infection (2.2% vs 3.8%; P < .001) 
  2. after adjusting for propensity score and covariates, histamine-2 receptor antagonists remained associated with less
    • GI hemorrhage (odds ratio 2.24; 95% CI, 1.81-2.76)
    • pneumonia (OR 1.2; 95% CI, 1.03-1.41)
    • Clostridium difficile infection (OR 1.29; 95% CI, 1.04-1.64)
  3. similar results were obtained in the propensity-matched models of 8,799 patients in each cohort

Abstract:  Wang. Histamine-2 Receptor Antagonists vs Proton Pump Inhibitors on Gastrointestinal Tract Hemorrhage and Maclaren. Infectious Complications in the Intensive Care Unit. JAMA Intern Med 2014;epublished February 17th

Journal of the American Medical Association:     Hypertension Guideline

Full Text:  James. 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults. Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8). JAMA 2014;311(5):507-520

January was a quite month, with no major research articles published. To make up for this the Critical Care Reviews Meeting was held on January 24th, with the presentations available here!



December 2013

British Journal of Anaesthesia:     Pulse Pressure Variation


November 2013

American Heart Association 2013 Meeting Update

New England Journal of Medicine:     Out-of-Hospital Cardiac Arrest

Nielsen and colleagues completed a randomized, parallel group study, comparing targeted temperature management of 33°C (n=473) with 36°C (n=466) in 950 unconscious adults (939 analyzed) after out-of-hospital cardiac arrest of presumed cardiac cause, and found:

  1. no difference in all cause mortality at trial end
    • 33°C group:  50%
    • 36°C group:  48% 
    • hazard ratio with a temperature of 33°C 1.06; 95% CI 0.89 to 1.28; P=0.51
  2. no difference in mortality or poor neurological function at 180 days
    • 33°C group:  54% 
    • 36°C group:  52% 
    • risk ratio 1.02; 95% CI 0.88 to 1.16; P=0.78
  3. using the modified Rankin scale, the comparable rate was 52% in both groups
    • risk ratio 1.01; 95% CI 0.89 to 1.14; P=0.87
  4. analyses adjusted for known prognostic factors were similar

Full Text:  Nielsen. Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest. N Engl J Med 2013;epublished November 17th


Journal of the American Medical Association:     Out-of-Hospital Cardiac Arrest

Kim et al completed a randomized, parallel group, controled trial, comparing standard care plus prehospital cooling (up to 2 L 4°C 0.9% saline) with standard care alone, in 1,359 cardiac arrest patients following return of spontaneous circulation, and found:

  1. cooling decreased mean core temperature by time of hospital arrival, compared with the control group:
    • ventricular fibrillation patients (n=583):  1.20 °C (95% CI −1.33 °C to −1.07 °C)
    • non ventricular fibrillation patients (n=776): 1.30 °C (95% CI −1.40 °C to −1.20 °C)
    • reduced the time to achieve a temperature of less than 34°C by about 1 hour compared with the control group
  2. no difference in survival to hospital discharge between intervention and control groups among patients with
    • VF patients (P=0.69)
      • cooling: 62.7% (95% CI 57.0%-68.0%)
      • control: 64.3% (95% CI 58.6%-69.5%) 
    • non VF patients (P=0.30)
      • cooling: 19.2% (95% CI 15.6%-23.4%) 
      • control: 16.3% (95% CI 12.9%-20.4%) 
  3. no difference in neurological status of full recovery or mild impairment at discharge 
    • VF patients (P=0.69)
      • cooling: 57.5% [(95% CI 51.8%-63.1%)
      • control: 61.9% (95% CI 56.2%-67.2%)
    • non VF patients (P=0.30)
      • cooling: 14.4% (95% CI 11.3%-18.2%)
      • control: 13.4% (95% CI10.4%-17.2%)
  4. cooling was associated with
    • increased rearrest in the field (P=0.008)
      • cooling: 26% (95% CI 22%-29%)
      • control: 21% (95% CI 18%-24%)
    • increased diuretic use 
    • increased pulmonary edema on first chest radiograph, which resolved within 24 hours after admission

Full Text:  Kim. Effect of Prehospital Induction of Mild Hypothermia on Survival and Neurological Status Among Adults With Cardiac Arrest:  A Randomized Clinical Trial. JAMA 2013;epublished November 17th


Journal of the American Medical Association:     Cardiopulmonary Resuscitation

Rubertsson et al performed an international, multicenter randomized trial comparing mechanical chest compressions (LUCAS Chest Compression System) combined with defibrillation during ongoing compressions (n = 1,300) with manual CPR according to guidelines (n = 1,289) in 2,589 patients with out-of-hospital cardiac arrest, and found:

  1. no difference in four-hour survival
    • mechanical CPR:  23.6%
    • manual CPR:       23.7%
    • risk difference –0.05%; 95% CI –3.3% to 3.2%; P > 0.99
  2. no difference in survival with a Cerebral Performance Category score of 1 or 2 
    • intensive care unit discharge
      • mechanical CPR:  7.5% 
      • manual CPR        6.4%
      • risk difference     1.18%; 95% CI –0.78% to 3.1% 
    • hospital discharge
      • mechanical CPR:  8.3%
      • manual CPR:       7.8%
      • risk difference     0.55%; 95% CI –1.5% to 2.6%
    • at 1 month
      • mechanical CPR:  8.1%
      • manual CPR:       7.3%
      • risk difference     0.78%; 95% CI, –1.3% to 2.8%
    • at 6 months
      • mechanical CPR:  8.5%
      • manual CPR:       7.6%
      • risk difference     0.86%; 95% CI –1.2% to 3.0%
  3. in survivors at 6 months with a Cerebral Performance Category score of 1 or 2
    • mechanical CPR:  99%
    • manual CPR:       94%

Full Text:  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


? Not Published Yet:     Nitrates in Acute Myocardial Infarction

Siddiqi and colleagues undertook an international, four centre randomized, interventional, safety/efficacy trial, comparing IV sodium nitrite (70 μmoles) with placebo over 5 minutes just before primary PCI in 229 patients with acute ST elevation myocardial infarction, and found:

  1. no difference in infarct size as a proportion of myocardial area at risk
    • at 6 - 8 days  (P=0.31)
      • nitrite:     22%
      • placebo:  20%    
    • at 6 months:
      • nitrite:    12% 
      • placebo: 14%
  2. no significant differences at 6-8 days or 6 months in
    • left ventricular ejection fraction
    • end systolic volume index
    • infarct size at 6 months
    • troponin
    • plasma creatine kinase

Summary Slide:  Siddiqi. Nitrites in Acute Myocardial Infarction (NIAMI) trial.


Journal of the American Medical Association:     Stroke Blood Pressure Control

He et al performed a randomized, multicentre, single-blind trial in 4,071 patients with nonthrombolysed ischemic stroke within 48 hours of onset and elevated systolic blood pressure, comparing antihypertensive treatment (aimed at lowering systolic blood pressure by 10% to 25% within the first 24 hours, achieving blood pressure less than 140/90 mm Hg within 7 days, and maintaining this level during hospitalization; n = 2,038) with discontinuation of all antihypertensive medications (control) during hospitalization (n = 2,033), and found:

  1. a larger reduction in mean systolic blood pressure within 24 hours with antihypertensive therapy
    • antihypertensive group:  166.7 mm Hg to 144.7 mm Hg (−12.7%)
    • control group:  165.6 mm Hg to 152.9 mm Hg (−7.2%)
    • difference −5.5% (95% CI −4.9 to −6.1%); absolute difference −9.1 mm Hg (95% CI −10.2 to −8.1); P  < 0.001
  2. lower mean systolic blood pressure at day 7with antihypertensive therapy
    • antihypertensive group:  137.3 mm Hg
    • control group:  146.5 mm Hg
    • difference −9.3 mm Hg (95% CI −10.1 to −8.4); P < 0.001
  3. no difference in primary outcome (combination of death and major disability at 14 days or hospital discharge)
    • antihypertensive group: 683 events
    • control group:  681 events
    • odds ratio 1.00 (95% CI 0.88 to 1.14); P = 0.98
  4. no difference in secondary composite outcome of death and major disability at 3-month posttreatment follow-up
    • 500 events
    • 502 events
    • odds ratio 0.99 (95% CI, 0.86 to 1.15); P =0 .93
Full Text:  He. Effects of Immediate Blood Pressure Reduction on Death and Major Disability in Patients With Acute Ischemic Stroke:  The CATIS Randomized Clinical Trial. JAMA 2013;epublished November 17th


Journal of the American College of Cardiology:     Cardiovascular Risk


October 2013

Canadian Journal of Anaesthesia:     Difficult Airway


Canadian Journal of Anaesthesia:     Difficult Airway


Critical Care Medicine:     Ventilator-Associated Pneumonia

Abstract:  Seguin. Effect of Oropharyngeal Povidone-Iodine Preventive Oral Care on Ventilator-Associated Pneumonia in Severely Brain-Injured or Cerebral Hemorrhage Patients: A Multicenter, Randomized Controlled Trial (SPIRIT study). Crit Care Review 2013;epublished October 7th


ESICM 2013 Meeting Update

Unpublished:     OPTIMISE

Pearse and colleagues presented the results of the OPTIMISE trial at the hot topics session of the ESICM meeting earlier this week in Paris. This was a large multi-centre, randomized, controlled study comparing the intervention of  haemodynamic management using fluid and dopexamine based on a minimally invasive cardiac output monitor derived algorithm (n=367), with a control of standard therapy (n=367), in patients undergoing largely elective major gastrointestinal surgery, and found:

  1. the overall compliance rate in both groups was 91%
  2. regarding fluid therapy
    1. no apparent difference in administered volume (intervention 4190 ml versus control 4024 ml)
    2. the intervention group received more colloid (colloid therapy was part of the interventional protocol)
  3. trends for improvement
    • primary outcome
      • a composite of death and complications at 30 days (intervention 36.6% versus control 44.4%; RR 0.84, 95% CI 0.71 - 1.01; p=0.07)
    • secondary outcomes
      • death at 180 days (intervention 7.7% versus 11.6%; RR 0.66, 95% CI 0.42 - 1.05, P=0.079)
      • infection (23.8% versus 29.7%; RR 0.80, 95% CI 0.63 - 1.02, P=0.079) 
  4. no difference in hospital stay (10 versus 11 days; P=0.054)


Journal of the American Medical Association:     Fluids

Annane and colleagues performed a multicenter, randomized, open label, assessment blinded, clinical trial, stratified by case mix (sepsis, trauma, or hypovolemic shock without sepsis or trauma), comparing colloids (n = 1,414; gelatins, dextrans, hydroxyethyl starches, or 4% or 20% of albumin) with crystalloids (n = 1,443; isotonic or hypertonic saline or Ringer's lactate solution) for all fluid interventions other than fluid maintenance throughout the ICU stay, and found:

  1. no difference in
    • 28 day mortality (colloids 25.4% versus crystalloids 27.0%, RR 0.96, 95% CI 0.88 - 1.04, P=0.26)
    • renal replacement therapy use (colloids 11.0% versus crystalloids 12.5%, RR 0.93, 95% CI 0.83 to 1.03, P=0.19)
  2. improved outcomes with colloid therapy
    • reduced 90 day mortality (30.7% versus 34.2%; RR 0.92, 95% CI 0.86 - 0.99; P=0.03)
    • more days alive without mechanical ventilation
      • by day 7 (mean: 2.1 versus 1.8 days; mean difference 0.30, 95% CI 0.09 to 0.48 days, P=0.01)
      • by day 28 (mean: 14.6 versus 13.5 days; mean difference, 1.10, 95% CI 0.14 to 2.06 days; P=0.01)
    • more days alive without vasopressor therapy
      • by day 7 (mean: 5.0 vs 4.7 days; mean difference 0.30, 95% CI −0.03 to 0.50 days; P=0.04) 
      • by day 28 day (mean: 16.2 vs 15.2 days; mean difference 1.04, 95% CI −0.04 to 2.10 days; P=0.03)

Full Text:  Annane. Effects of Fluid Resuscitation With Colloids vs Crystalloids on Mortality in Critically Ill Patients Presenting With Hypovolemic Shock. The CRISTAL Randomized Trial. JAMA 2013;epublished October 9th


Journal of the American Medical Association:     Skeletal Muscle Wasting

Puthucheary and colleagues completed an observational study characterizing skeletal muscle wasting in 63 critically ill patients anticipated to be intubated for longer than 48 hours, to spend more than 7 days in critical care, and to survive ICU stay, and found:

  1. mean APACHE II score was 23.5 (95% CI 21.9-25.2)
  2. significant reductions in the rectus femoris cross-sectional area (CSA) at day 10 (−17.7%, 95% CI −25.9% to 8.1%, P<0.001)
  3. in 28 patients assessed by 3 skeletal muscle assessment methods on days 1 and 7
    • rectus femoris CSA decreased by 10.3% (95% CI 6.1% to 14.5%) 
    • muscle fiber CSA decreased by 17.5% (95% CI, 5.8% to 29.3%)
    • ratio of protein to DNA decreased by 29.5% (95% CI 13.4% to 45.6%)
  4. rectus femoris CSA decrease was greater in patients who experienced multi-organ failure, compared with single-organ failure, at
    • day 3 (−8.7% versus −1.8%, P=0 .03)
    • day 7 (−15.7% versus  −3.0% P <0 .001) 
  5. myofiber necrosis occurred in 20 of 37 patients (54.1%).
  6. the pattern of intracellular signaling supported
    • increased protein breakdown (n = 9, r = −0.83, P= 0.005)
    • decreased protein synthesis (n = 9, r = −0.69, P= 0.04)

Full Text:  Puthucheary. Acute Skeletal Muscle Wasting in Critical Illness. JAMA 2013;310(15):1591-1600


Journal of the American Medical Association:     Beta Blockade in Sepsis

Morelli and colleagues undertook an open-label, randomized phase 2 study in 154 critically ill patients with septic shock and a heart rate of 95/min or higher, requiring high-dose norepinephrine to maintain a mean arterial pressure of 65 mm Hg or higher, and compared a continuous infusion of esmolol titrated to maintain heart rate between 80/min and 94/min for their ICU stay (n=77) with standard treatment (n=77), and found:

  1. targeted heart rates were achieved in all patients in the esmolol group compared with those in the control group
  2. esmolol was associated with (median AUC):
    • a greater reduction in heart rate in the first 96 hours:  −28/min (IQR −37 to −21) versus −6/min (95% CI −14 to 0)
    • increased stroke volume index: 4 mL/m2: (IQR −1 to 10) vs 1 mL/m2 (IQR −3 to 5; P = 0.02)
    • increased left ventricular stroke work index: 3 mL/m2 (IQR 0 to 8) versus 1 mL/m2 (IQR −2 to 5; P = 0.03)
    • decreased arterial lactataemia:,  −0.1 mmol/L (IQR −0.6 to 0.2) versus 0.1 mmol/L (IQR −0.3 for 0.6; P = 0.007)
    • decreased norepinephrine dose: −0.11 μg/kg/min (IQR −0.46 to 0.02) versus −0.01 μg/kg/min (IQR −0.2 to 0.44) (P = 0.003)
    • reduced fluid requirements:  3975 mL/24 h (IQR 3663 to 4200) versus 4425 mL/24 h (IQR 4038 to 4775) (P < 0.001)
    • reduced 28 day mortality (49.4% versus 80.5%; adjusted hazard ratio 0.39; 95% CI 0.26 to 0.59; P < 0.001)

Full Text:  Morelli. Effect of Heart Rate Control With Esmolol on Hemodynamic and Clinical Outcomes in Patients With Septic Shock. A Randomized Clinical Trial. JAMA 2013;epublished October 9th


Journal of the American Medical Association:     Statins in VAP

Papazian and colleagues completed a randomized, placebo-controlled, double-blind, parallel-group, multi-center trial in 300 critically ill patients receiving invasive mechanical ventilation for more than 2 days and with suspected ventilator-associated pneumonia, comparing simvastatin 60 mg with placebo,and found:

  1. the study was stopped for futility at the first scheduled interim analysis
  2. no difference in 28 day mortality (simvastatin 21.2% versus placebo 15.2%P = 0.10; hazard ratio 1.45, 95% CI 0.83 to 2.51; between-group difference 6.0%, 95% CI −3.0% to 14.9%)
  3. 93% in the simvastatin group and 89% in the placebo group were naive to statin therapy at ICU admission
    • in statin-naive patients, a trend for worsened 28 day mortality with statins 21.5% versus 13.8% (P = 0.054) (between-group difference 7.7%, 95% CI −1.8% to 16.8%)
  4. no significant differences regarding
    • mortality: 14 day, ICU, or hospital
    • duration of mechanical ventilation
    • changes in SOFA score

Full Text:  Papazian. Effect of Statin Therapy on Mortality in Patients With Ventilator-Associated Pneumonia. A Randomized Clinical Trial.   JAMA 2013;epublished October 9th


Torres. Corticosteroids for Severe Community-Acquired Pneumonia. (Unpublished)

In a parallel group, randomized controlled trial Torres and colleagues compared methylprednisolone 0.5 mg/kg 12 hourly (n=31) with matching placebo (n=29) for five days in 60 patients, and found:

  1. steroid therapy was associated with
    • reduced rates of treatment failure (primary outcome) 13% versus 31% (p=0.021), (crude odds ratio 0.34, 95% CI 0.14 - 0.87, p=0.024) (adjusted OR 0.34, 95% CI 0.12 - 0.96, p=0.04)
    • reduced mortality 10% versus 15%
    • reduced inflammatory cytokine levels
    • no reduction in length of stay (10.5 days versus 11 days)
  2. treatment failure was largely due to worsening of the chest radiograph

(these results are provisional as I was taking notes during the presentation)


Journal of the American Medical Association:     Bacterial Meningitis

Full Text:  Mourvillier. Induced Hypothermia in Severe Bacterial Meningitis:  A Randomized Clinical Trial. JAMA 2013;epublished October 8th


Journal of the American Medical Association:     Coronary Stents & Surgery

Full Text:  Hawn. Risk of Major Adverse Cardiac Events Following Noncardiac Surgery in Patients With Coronary Stents. JAMA 2013;epublished October 7th


Journal of the American Medical Association:     ICU Infections

Harris and colleagues performed a multi-centre cluster-randomized trial in 20 American ICUs (26,180 patients, 92,241 swabs) comparing the intervention of wearing of gloves and gown for all patient contact and when entering any patient room with the control of following current Centers for Disease Control and Prevention guidelines for infection control measures, and found:

  1. for the primary outcome
    • no difference in the rates of acquisition of MRSA or VRE (difference −1.71 acquisitions per 1000 person-days, 95% CI −6.15 to 2.73; P = 0.57)
    • intervention ICUs had a decrease in the primary outcome of MRSA or VRE from 21.35 acquisitions per 1000 patient-days (95% CI 17.57 to 25.94) in the baseline period to 16.91 acquisitions per 1000 patient-days (95% CI, 14.09 to 20.28) in the study period
    • control ICUs had a decrease in MRSA or VRE from 19.02 acquisitions per 1000 patient-days (95% CI 14.20 to 25.49) in the baseline period to 16.29 acquisitions per 1000 patient-days (95% CI 13.48 to 19.68) in the study period
  2. for secondary outcomes
    • no difference in VRE acquisition with the intervention (difference  0.89 acquisitions per 1000 person-days; 95% CI −4.27 to 6.04, P =0 .70)
    • for MRSA, there were fewer acquisitions with the intervention (difference −2.98 acquisitions per 1000 person-days; 95% CI −5.58 to −0.38; P = 0.046)
    • universal glove and gown use decreased health care worker room entry (4.28 vs 5.24 entries per hour, difference −0.96; 95% CI −1.71 to −0.21, P = 0.02)
    • increased room-exit hand hygiene compliance (78.3% vs 62.9%, difference 15.4%; 95% CI 8.99% to 21.8%; P  = 0.02) 
    • no difference in adverse events (58.7 events per 1000 patient days vs 74.4 events per 1000 patient days; difference −15.7; 95% CI −40.7 to 9.2, P = 0.24)

Full Text:  Harris. Universal Glove and Gown Use and Acquisition of Antibiotic-Resistant Bacteria in the ICU: A Randomized Trial. JAMA 2013;epublished October 4th    


New England Journal of Medicine:     Long-Term Cognitive Impairment after Critical Illness

Pandharipande and colleagues observed 821 critically ill adults with respiratory failure or shock to examine the effects of critical illness on cognitive function, and found:

  1. cognitive impairment was present in 6% at baseline
  2. delirium developed in 74% during the hospital stay
  3. at 3 months
    • 40% had global cognition scores 1.5 SD below population means (similar to patients with moderate traumatic brain injury)
    • 26% had scores 2 SD below population means (similar to patients with mild Alzheimer's disease)
  4. at 12 months
    • deficits persisted in both older and younger patients 
    • 34% of all assessed patients had scores similar to patients with moderate traumatic brain injury
    • 24% of all assessed patients had scores similar to patients with mild Alzheimer's disease
  5. a longer duration of delirium was independently associated with worse
    • global cognition at 3 (p=0.001) and 12 months (P=0.04)
    • executive function at 3 (P=0.004) and 12 months (P=0.007) 
  6. sedative or analgesic medications was not consistently associated with cognitive impairment at 3 and 12 months

Abstract:  Pandharipande. Long-Term Cognitive Impairment after Critical Illness. N Engl J Med 2013;369:1306-1316


September 2013

Journal of the American Medical Association:     Severe Alcoholic Hepatitis

Mathurin and colleagues performed a multicenter, randomized, double-blind trial in 270 heavy drinkers with severe biopsy-proven alcoholic hepatitis, comparing a combination (n=133) of prednisolone (40 mg OD) and pentoxifylline (400 mg TID) with a combination (n=137) of prednisolone (40 mg OD) with matching placebo for 28 days, and found no difference between groups in:

  1. 6 month survival (prednisolone-pentoxifylline 69.9% (95% CI 62.1%-77.7%) versus prednisolone-placebo 69.2% (95% CI 61.4%-76.9%); p=0 .91)
  2. response to therapy at 7 days, as assessed by the Lille model (prednisolone-pentoxifylline 0.41 (95% CI 0.36-0.46) versus prednisolone-placebo 0.40 (95% CI 0.35-0.45); p=0 .80)
  3. a trend for reduced incidence of hepatorenal syndrome at 6 months (pentoxifylline-prednisolone 8.4% (95% CI 4.8%-14.8%) versus placebo-prednisolone groups 15.3% (95% CI, 10.3%-22.7%); p=0.07)

Abstract:  Mathurin. Prednisolone With vs Without Pentoxifylline and Survival of Patients With Severe Alcoholic HepatitisA Randomized Clinical Trial. JAMA 2013;310(10):1033-1041


American Journal of Gastroenterology:     Acute Pancreatitis Guideline


New England Journal of Medicine:     Direct Oral Anticoagulants

Eikelboom and colleagues performed a randomized, phase 2 dose-validation study in 252 patients, comprising two cohorts (aortic- or mitral-valve replacement either within the past 7 days or at least 3 months earlier), comparing dose adjusted dabigtran with dose adjusted warfarin for the prevention of venothromboembolism. They reported:

  1. early trial termination due to excessive harm in the dabigatran arm (dabigatran versus warfarin)
    • strokes (n=9 (5%) versus n=0 (0%))
    • myocardial infarction (n=3 (2%) versus n=0 (0%))
    • death (n=1 versus n=2)
    • composite of stroke, transient ischemic attack, systemic embolism, myocardial infarction, or death (n=15 (9%) versus n=4 (5%); hazard ratio 1.94; 95% CI 0.64 to 5.86; P=0.24)
    • major bleeding (n=7 (4%) versus n=2 (2%))  
    • any bleeding (n=45 (27%) versus n=10 (12%); hazard ratio 2.45; 95% CI 1.23 to 4.86; P=0.01)
    • Increased bleeding with dabigatran was noted in both cohorts

Full Text:  Eikelboom. Dabigatran versus Warfarin in Patients with Mechanical Heart Valves (RE-ALIGN study). New Eng J Med 2013;epublished September 1st   


The Hokusai-VTE Investigators completed an international, multi-centre, randomized, double-blind, noninferiority study in 8,292 patients with acute venous thromboembolism, who had initially received heparin, comparing edoxaban (n=4,118) (either 60 mg once daily or dose adjusted to 30 mg once daily), with warfarin (n=4,122), for 3 to 12 months, and found:

  1. for the primary efficacy outcome (recurrent symptomatic venous thromboembolism), edoxaban was noninferior to warfarin (edoxban 3.2% versus warfarin 3.5%; hazard ratio 0.89; 95% CI 0.70 to 1.13; P<0.001 for noninferiority).
  2. less major or clinically relevant nonmajor bleeding with edoxaban (8.5% versus 10.3%; hazard ratio 0.81; 95% CI 0.71 to 0.94; P=0.004 for superiority)
  3. in patients with pulmonary embolism associated right ventricular dysfunction (n=938), there was a reduced rate of recurrent venous thromboembolism with edoxaban (3.3% versus 6.2%; hazard ratio 0.52; 95% CI 0.28 to 0.98)
  4. no difference in adverse events between the two groups.

Full Text:  Hokusai-VTE Investigators. Edoxaban versus Warfarin for the Treatment of Symptomatic Venous Thromboembolism (Hokusai-VTE study). New Eng J Med 2013;epublished September 1st


New England Journal of Medicine:     Coronary Thrombus Aspiration

Using the Swedish Coronary Angiography and Angioplasty Registry (SCAAR), Fröbert et al undertook a multicenter, prospective, randomized, controlled, open-label clinical trial in 7,244 patients with STEMI undergoing PCI, and compared manual thrombus aspiration followed by PCI with PCI alone, and found:

  1. no 30-day mortality effect (aspiration group 2.8% versus PCI-only group 3.0%; hazard ratio 0.94; 95% CI 0.72 to 1.22; P=0.63)
  2. a trend for reduced rates of hospitalization for recurrent myocardial infarction at 30 days with aspiration (0.5% versus 0.9%; hazard ratio 0.61; 95% CI 0.34 to 1.07; P=0.09)
  3. a trend for reduced rates of stent thrombosis with aspiration (0.2% versus 0.5%; hazard ratio 0.47; 95% CI 0.20 to 1.02; P=0.06)
  4. no differences between groups for stroke or neurologic complications at discharge (P=0.87)

Full Text: Fröbert. Thrombus Aspiration during ST-Segment Elevation Myocardial Infarction. New Eng J Med 2013;epublished September 1st   


New England Journal of Medicine:     Prasugrel before Percutaneous Coronary Intervention

Montalescot and colleagues performed an international, multi-centre, phase 3, randomized, double-blind, event-driven study in 4,033 patients with non-ST elevation acute coronary syndrome and a positive troponin level scheduled to undergo coronary angiography within 48 hours after randomization, comparing administering prasugrel 30mg (pretreatment group) at the time of diagnosis versus administering it after coronary angiography if PCI was indicated (pretreatment group additional 30mg, late treatment group 60mg). They found:

  1. no difference in the rate of the primary efficacy end point  (composite of death from cardiovascular causes, myocardial infarction, stroke, urgent revascularization, or glycoprotein IIb/IIIa inhibitor rescue therapy at day 7) (hazard ratio with pretreatment 1.02; 95% CI 0.84 to 1.25; P=0.81)
  2. increased rate of Thrombolysis in Myocardial Infarction (TIMI) major bleeding episodes at day 7 with pretreatment (hazard ratio 1.90; 95% CI 1.19 to 3.02; P=0.006)
  3. rates of TIMI major bleeding and life-threatening bleeding not related to CABG were increased by a factor of 3 and 6, respectively

Full Text:  Montalescot. Pretreatment with Prasugrel in Non–ST-Segment Elevation Acute Coronary Syndromes (ACCOAST study). New Eng J Med 2013;epublished September 1st    


New England Journal of Medicine:     Preventive Angioplasty

Wald et al performed a multi-centre, randomized controlled trial in 465 patients with acute STEMI undergoing infarct-artery PCI, and compared preventive (non-infarct artery) PCI (n=234) with no preventive PCI (n=231). They reported:

  1. after a mean follow up of 23 months, the trial was terminated early by the data and safety monitoring committee
  2. reduced rates of the primary outcome (a composite of death from cardiac causes, nonfatal myocardial infarction) with preventive PCI (n=21 versus n=53, hazard ratio 0.35; 95% CI 0.21 to 0.58; P<0.001)
  3. reduced hazard ratio with preventive PCI for
    • death from cardiac causes 0.34 (95% CI 0.11 to 1.08)
    • nonfatal myocardial infarction 0.32 (95% CI 0.13 to 0.75)
    • refractory angina 0.35 (95% CI 0.18 to 0.69) 

Full Text:  Wald. Randomized Trial of Preventive Angioplasty in Myocardial Infarction (PRAMI study). New Eng J Med 2013;epublished September 1st   


New England Journal of Medicine:     Acute Pericarditis

Imazio et al completed a multicenter, randomized, placebo controlled, blinded trial in 240 patients  with acute pericarditis, evaluating colchicine (n=120, 0.5 mg twice daily for 3 months or dose adjusted 0.5 mg once daily), in addition to conventional antiinflammatory therapy with aspirin or ibuprofen, and found:

  1. colchicine therapy was associated with reduced rates of
    • primary outcome occurance (incessant or recurrent pericarditis) (16.7% versus 37.5%; relative risk reduction 0.56; 95% CI 0.30 to 0.72; NNT 4; P<0.001)
    • symptom persistence at 72 hours (19.2% versus 40.0%, P=0.001),
    • recurrences per patient (0.21 versus 0.52, P=0.001)
    • hospitalization (5.0% versus 14.2%, P=0.02).
    • remission at 1 week (85.0% versus 58.3%, P<0.001)
  2. no difference in adverse effects or rates of study-drug discontinuation betweeen the two study groups

Full Text:  Imazio. A Randomized Trial of Colchicine for Acute Pericarditis (ICAP Study). New Eng J Med 2013;epublished September 1st 


Journal of the American Medical Association:     Otamixaban in NSTE Coronary Syndromes

Steg and colleagues undertook an international, multi-centre, randomized, double-blind, active-controlled superiority trial in 13,229 patients with non-ST elevation acute coronary syndrome and a planned early invasive strategy, comparing otamixaban, a novel intravenous direct factor Xa inhibitor, with unfractionated heparin plus downstream eptifibatide, and found:

  1. no difference in the incidence of the primary efficacy outcome (a composite of all-cause death or new myocardial infarction at day 7); otamixaban 5.5% (279 of 5105 patients) versus unfractionated heparin plus eptifibatide 5.7% (310 of 5466 patients); adjusted relative risk 0.99; 95% CI 0.85-1.16; P =0 .93)
  2. no differences in secondary outcomes, including procedural thrombotic complications
  3. an increase with otamixaban therapy in the primary safety outcome of Thrombosis in Myocardial Infarction (TIMI) major or minor bleeding at day 7 (3.1% vs 1.5%; RR 2.13; 95% CI 1.63-2.78; P < 0.001)


August 2013

Lancet Respiratory Medicine:     Delirium

In a double-blind, placebo-controlled randomised trial comparing haloperidol (n=71) 2.5 mg IV 8 hourly, with 0.9% saline (n=70), regardless of coma or delirium status, in general critically ill mechanically ventilated patients within 72 hours of ICU admission, Page and colleagues found:

  1. no difference in the number of days alive, without delirium, and without coma (median 5 days [IQR 0—10] vs 6 days [0—11] days; p=0·53)
  2. Numerically more oversedation with haloperidol (11 patients versus 6)
  3. No difference in rates of QTc prolongation (haloperidol 7 patients versus placebo 6).
  4. No serious adverse events with haloperidol

Abstract:  Page. Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (Hope-ICU): a randomised, double-blind, placebo-controlled trial. Lancet Respiratory Medicine 2013;epublished August 21st


July 2013

New England Journal of Medicine:     Low Tidal Volume Ventilation

In a multicenter, randomized, double-blind, parallel-group trial, Futier and colleagues compared lung-protective ventilation (n=200, tidal volume of 6 to 8 mL/kg predicted body weight, positive end-expiratory pressure of 6 to 8 cm water, and recruitment maneuvers repeated every 30 minutes after tracheal intubation) with nonprotective ventilation (n=200, tidal volume of 10 to 12 mL/kg, and neither positive end-expiratory pressure nor recruitment maneuvers) in 400 adults at intermediate to high risk of pulmonary complications after major abdominal surgery. Lung protective ventilation was associated with a reduced incidence of the primary outcome, a composite of major pulmonary and extrapulmonary complications occurring within the first 7 days after surgery (10.5% versus 27.5%; relative risk 0.40; 95% CI 0.24 to 0.68; P=0.001). Protective ventilation was also associated with both a reduced requirement for non-invasive ventilation (5% versus 17%; relative risk 0.29; 95% CI 0.14 to 0.61; P=0.001) and shorter length of hospital stay (mean difference −2.45 days; 95% CI −4.17 to −0.72; P=0.006).

Abstract:  Futier. A Trial of Intraoperative Low-Tidal-Volume Ventilation in Abdominal Surgery (IMPROVE study). N Engl J Med 2013; 369:428-437


Heart:     Perioperative Beta Blockade

Following the controversy regarding the veracity of the Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography (DECREASE) family of perioperative β-blockers trials, Bouri and colleagues performed meta analyses on randomised controlled trials of the initiation of β-blockers before non-cardiac surgery, examining the DECREASE trials and non-DECREASE trials seperately. In nine non-DECREASE trials (n=10 529, 291 deaths) the initiation of a course of β-blockers before surgery caused a 27% risk increase in 30-day all-cause mortality (p=0.04), and are significantly different to the results of the DECREASE studies meta analysis (p=0.05 for divergence). In the non-DECREASE studies, which were dominated by one large study, β-blockade reduced non-fatal myocardial infarction (RR 0.73, p=0.001) but increased stroke (RR 1.73, p=0.05) and hypotension (RR 1.51, p<0.00001).

Full Text: Bouri. Meta-analysis of secure randomised controlled trials of β-blockade to prevent perioperative death in non-cardiac surgery. Heart 2013;epublished July 31st


Mayo Clinic Proceedings:     Evidence Reversal

In an attempt to identify medical practices that offer no net benefits, Prasad and colleagues reviewed all original articles published from 2001-2010 in the New England Journal of Medicine, the highest impact medical journal. 2044 original articles were reviewed, with 1344 concerning a medical practice, of which 981 articles (73.0%) examined a new medical practice, whereas 363 (27.0%) tested an established practice. 947 studies (70.5%) had positive findings, and 397 (29.5%) negative findings. In 756 articles, the new medical practice surpassesed current standard of care, in 165 articles, the new practice was no better than current practice, in 146 articles, current practice was not superior to supposedly inferior therapies, 138 articles provided reaffirmations, where an existing practice was found to be better than a lesser standard, while 139 were inconclusive. Of the 363 articles testing standard of care, 146 (40.2%) reversed that practice, whereas 138 (38.0%) reaffirmed it. These results occured across all classes of medical practice.

Full Text:  Prasad. A Decade of Reversal: An Analysis of 146 Contradicted Medical Practices. Mayo Clinic Proceedings 2013;epublished July 22nd

Editorial:  Ioannidis. How Many Contemporary Medical Practices Are Worse Than Doing Nothing or Doing Less? Mayo Clinic Proceedings 2013;epublished July 22nd


Journal of the American Medical Association:     Cardiac Arrest

Mentzelopoulos and colleagues completed a randomized, double-blind, placebo-controlled, parallel-group trial in 268 consecutive patients with cardiac arrest and compared a regimen of adrenaline (1mg/CPR cycle of approximately 3 minutes), plus vasopressin (20 IU/CPR cycle for the first 5 cycles) plus methylprednisolone (40 mg in the first cycle only) {VSE group, n=130) with adrenaline (1mg/CPR cycle) plus saline placebo {control group, n=138).  In survivors, post resuscitation shock was treated with stress-dose hydrocortisone (300 mg daily for 7 days maximum and gradual taper) (VSE group, n = 76) or saline placebo (control group, n = 73). VSE therapy was associated with both a higher probability for return of spontaneous circulation of 20 minutes or longer (primary outcome) (109/130 [83.9%] vs 91/138 [65.9%]; odds ratio  2.98; 95% CI 1.39-6.40; P = 0.005) and survival to hospital discharge with cerebral performance category score of 1 or 2 (18/130 [13.9%] vs 7/138 [5.1%]; OR 3.28; 95% CI 1.17-9.20; P = 0.02). Post resuscitation patients with shock and treated with VSE had higher probability for survival to hospital discharge with cerebral performance category scores of 1 or 2 (16/76 [21.1%] vs 6/73 [8.2%]; OR 3.74; 95% CI 1.20-11.62; P  = 0.02), improved hemodynamics and central venous oxygen saturation, and less organ dysfunction. There was no difference in adverse events.

Abstract:  Mentzelopoulos. Vasopressin, Steroids, and Epinephrine and Neurologically Favorable Survival After In-Hospital Cardiac Arrest: A Randomized Clinical Trial. JAMA 2013;310(3):270


June 2013

New England Journal of Medicine:     Stroke

In a Chinese randomized, double-blind, placebo-controlled trial in 5170 patients within 24 hours of a minor ischemic stroke or high-risk transient ischemic attack, the combination of clopidogrel (initially 300 mg, followed by 75 mg per day for 90 days) and aspirin (75 mg per day for the first 21 days), in comparison with placebo plus aspirin (75 mg per day for 90 days), was associated with a reduction in the occurance of stroke at 90 days (8.2% versus 11.7%; hazard ratio 0.68; 95% CI 0.57 to 0.81; P<0.001). There was no difference in the incidence of moderate or severe hemorrhage (0.3% both groups), or haemorhagic stroke (also 0.3% both groups).

Abstract:  Wang. Clopidogrel with Aspirin in Acute Minor Stroke or Transient Ischemic Attack. New Eng J Med 2013;epublished June 26th

Editorial:  Hankey. Dual Antiplatelet Therapy in Acute Transient Ischemic Attack and Minor Stroke. New Eng J Med 2013;epublished June 26th


American Journal of Respiratory and Critical Care Medicine:     Acute Lung Injury

In a cohort of 115 consecutive patients (1000 patients in main EDEN trial) within 48 hours of developing acute lung injury requiring mechanical ventilation, randomized to receive full or trophic (20% target) enteral feeding for 6 days, there was no difference in 6 month and 1 year outcomes in physical and cognitive performance. However, EDEN survivors demonstrated impairments in 6-minute walk distance (64% predicted at 6 months and 66% predicted at 12 months) and cognition (impairment in 36% at 6 months and 25% 12 months), with improvements in both measures over the 6 month period (p=0.011 and p=0.001, respectively, for difference between assessments).

Abstract:  Needham. Physical and Cognitive Performance of Acute Lung Injury Patients One Year after Initial Trophic vs Full Enteral Feeding: EDEN Trial Follow-Up. Am J Respir Crit Care Med 2013;epublished June 2nd


Critical Care Medicine:     Fluid Responsiveness

Using data from healthy controls studies (n = 1), ICU studies (n = 22) and operating room studies (n = 20), Marik updated his previous systematic review and meta analysis examining the utility of central venous pressure to predict fluid responsiveness. Just over half of patients were fluid responsive (57%± 13%). Overall, CVP had no ability to predict fluid responsiveness (AUC 0.56, 95% CI 0.54–0.58) with no improvement in subgroups; ICU patients 0.56 (95% CI, 0.52–0.60 and OR patients 0.56 (95% CI, 0.54–0.58). Similarly, correlation between baseline CVP and change in stroke volume index/cardiac index was also poor, being 0.18 (95% CI, 0.1–0.25) overall, 0.28 (95% CI, 0.16–0.40) in ICU patients, and 0.11 (95% CI, 0.02–0.21) in OR patients.

Abstract:  Marik. Does the Central Venous Pressure Predict Fluid Responsiveness? An Updated Meta-Analysis and a Plea for Some Common Sense. Critical Care Medicine 2013;41(7):1774-1781


New England Journal of Medicine:     MERS-CoV

Assiri et al describe a cluster of 23 cases of healthcare associated MERS-CoV occuring between April 1st and May 23rd 2013 in Saudi Arabia. By June 15th, the mortality rate was 65% (n=15), with the remained either having recovered (n=6, 26%) or remaining hospitalized (n=2, 9%). Symptoms included fever (87%), cough (87%), dyspnoea (48%) and GI symptoms (35%), with 87% presenting with an abnormal chest radiograph. The majority of infections (21/23) were acquired by person-to-person transmission in hemodialysis units, intensive care units, or in-patient units, with a median incubation period of 5.2 days.

Full Text:  Assiri. Hospital Outbreak of Middle East Respiratory Syndrome Coronavirus. New Eng J Med 2013;epublished June 19th


Chest:     Ventilator-Associated Pneumonia

Dimopoulos performed a systematic review and meta-analysis, totalling 4 randomized controlled trials, comparing short (7-8 days)- with long (10-15 days)-duration antibiotic regimens for ventilator-associated pneumonia.There was no difference in mortality (odds ratio 1.20, 95% CI 0.84-1.72, p=0.32), or in relapses, although long-course treatment was associated with a strong trend to lower relapses (OR 1.67, 95% CI 0.99-2.83, p=0.06). Short-course treatment was associated with an increase in antibiotic-free days, with a pooled weighted mean difference of 3.40 days ( 95% CI 1.43 to 5.37, p<0.001).

Abstract:  Dimopoulos. Short- versus long-duration antibiotic regimens for ventilator-associated pneumonia: a systematic review and meta-analysis. Chest 2013;epublished June 20th


Critical Care Medicine:     Acute Kidney Injury

McGuinness et al completed a phase IIb multicenter double-blind randomized controlled trial, comparing sodium bicarbonate infusion (n=215) with 0.9% saline infusion (n=212) for the prevention of cardiac surgery–associated acute kidney injury in 427 at risk patients. There was no difference in the incidence in AKI, (bicarbonate 47% versus saline 44%; p=0.58), duration of either ventilation, ICU stay, or hospital stay, or mortality.

Abstract:  McGuinness. Sodium Bicarbonate Infusion to Reduce Cardiac Surgery-Associated Acute Kidney Injury: A Phase II Multicenter Double-Blind Randomized Controlled Trial. Critical Care Medicine 2013;41(7):1599-1607


British Journal of Haematology:     Red Cell Transfusion Guideline


New England Journal of Medicine:     Intracerebral Haemorrhage

Anderson and colleagues completed a randomized, controlled trial in 2,839 patients with a spontaneous intracerebral hemorrhage within the previous 6 hours and who had elevated systolic blood pressure, comparing a target systolic blood pressure  <140 mm Hg within 1 hour with guideline-recommended treatment of a target systolic level of <180 mm Hg, with physician's using anti-hypertensives of their choice. In those for whom the primary outcome (death or major disability) could be determined, 52.0% (719/1382) receiving intensive treatment, as compared with 55.6% (785/1412)  receiving guideline-recommended treatment, had a primary outcome event (odds ratio with intensive treatment 0.87; 95% CI 0.75 to 1.01; P=0.06). Ordinal analysis showed significantly lower modified Rankin scores with intensive treatment (odds ratio for greater disability 0.87; 95% CI, 0.77 to 1.00; P=0.04). There were no differences in mortality (intensive-treatment group 11.9% versus standard-treatment group 12.0%), the percentage of deaths attributed to the direct effect of the intracerebral hemorrhage (61.4% versus 65.3%, respectively) or nonfatal serious adverse events (23.3% versus 23.6% respectively).

Full Text:  Anderson. Rapid Blood-Pressure Lowering in Patients with Acute Intracerebral Hemorrhage (INTERACT2). N Eng J Med 2013;epublished May 29th  


New England Journal of Medicine:     ICU Decolonization

Huang et al performed a pragmatic, cluster-randomized trial in 43 hospitals (74 ICUs, 74,256 patients) comparing three methods of infection control, with all adult ICUs in a given hospital assigned to the same strategy: (1) MRSA screening and isolation; (2) targeted decolonization (i.e., screening, isolation, and decolonization of MRSA carriers); (3) universal decolonization (i.e., no screening, and decolonization of all patients). Comparing the intervention period with the baseline period, universal decolonization resulted in a significantly greater reduction in the hazard of MRSA-positive clinical cultures than did screening and isolation (hazard ratio 0.63; 95% CI 0.52 to 0.75 versus hazard ratio  0.92; 95% CI 0.77 to 1.10; P=0.003 for test of all groups being equal). For ICU-attributable MRSA bloodstream infections, universal decolonization was more effective than the other strategies (HR 0.72, 95% CI 0.48 to 1.08 versus HR 1.23, 95% CI 0.82 to 1.85 for screening and isolation and HR 1.23, 95% CI 0.82 to 1.85 for targeted decolonization). For ICU-attributable bloodstream infection from any pathogen, universal decolonization resulted in a significantly greater reduction in the hazard of infection (HR 0.56, 95% CI 0.49 to 0.65) than either screening and isolation (HR 0.99; 95% CI 0.84 to 1.16; P<0.001) or targeted decolonization (HR 0.78; 95% CI 0.66 to 0.91; P=0.04). There was no difference in mortality between groups, although the trial was inadequately powered for this outcome.

Full Text:  Huang. Targeted versus Universal Decolonization to Prevent ICU Infection. N Eng J Med 2013;epublished May 29th


May 2013

Journal of the American Medical Association:     Tracheostomy

Abstract:  Young. Effect of Early vs Late Tracheostomy Placement on Survival in Patients Receiving Mechanical Ventilation: The TracMan Randomized Trial. JAMA 2013;309(20):2121


Lancet Respiratory Medicine:     Asthma

Abstract:  Goodacre. Intravenous or nebulised magnesium sulphate versus standard therapy for severe acute asthma (3Mg trial): a double-blind, randomised controlled trial. Lancet Respiratory Medicine 2013;epublished May 17th


Journal of the American Medical Association:     Myocardial Infarction

Full Text:  Jiang. Effect of Escitalopram on Mental Stress–Induced Myocardial Ischemia:  Results of the REMIT Trial. JAMA 2013;309(20):2139


Journal of the American Medical Association:     COPD Exacerbation

Full Text: Leuppi. Short-term vs Conventional Glucocorticoid Therapy in Acute Exacerbations of Chronic Obstructive Pulmonary Disease: The REDUCE Randomized Clinical Trial. JAMA 2013;epublished May 21st


American Thoracic Society Meeting Philadelphia 2013

Journal of the American Medical Association:     Music Therapy

Azoulay and colleagues performed a multi-centre randomized trial examining whether listening to self-initiated patient-directed music (PDM) reduced anxiety and sedative exposure during ventilatory support in 373 critically ill patients. Three groups were compared, self-initiated PDM (n = 126) with preferred selections tailored by a music therapist whenever desired while receiving ventilatory support, self-initiated use of noise-canceling headphones (NCH; n = 122), or usual care (n = 125). 86% were white, 52% were female, and the mean (SD) age was 59 (14) years. The patients had a mean (SD) Acute Physiology, Age and Chronic Health Evaluation III score of 63 (21.6) and a mean (SD) of 5.7 (6.4) study days. Patients in the PDM group listened to music for a mean (SD) of 79.8 (126) (median [range], 12 [0-796]) minutes/day. Patients in the NCH group wore the noise-abating headphones for a mean (SD) of 34.0 (89.6) (median [range], 0 [0-916]) minutes/day. The mixed-models analysis showed that at any time point, patients in the PDM group had an anxiety score that was 19.5 points lower (95% CI, −32.2 to −6.8) than patients in the usual care group (P = .003). By the fifth study day, anxiety was reduced by 36.5% in PDM patients. The treatment × time interaction showed that PDM significantly reduced both measures of sedative exposure. Compared with usual care, the PDM group had reduced sedation intensity by −0.18 (95% CI −0.36 to −0.004) points/day (P = 0.05) and had reduced frequency by −0.21 (95% CI, −0.37 to −0.05) points/day (P = 0.01). The PDM group had reduced sedation frequency by −0.18 (95% CI −0.36 to −0.004) points/day versus the NCH group (P = 0.04). By the fifth study day, the PDM patients received 2 fewer sedative doses (reduction of 38%) and had a reduction of 36% in sedation intensity.

Full Text: Chlan. Effects of Patient-Directed Music Intervention on Anxiety and Sedative Exposure in Critically Ill Patients Receiving Mechanical Ventilatory Support: A Randomized Clinical Trial. JAMA 2013;epublished May 20th  

Journal of the American Medical Association:     Parenteral Nutrition

Doig et al completed a multicenter, randomized, single-blind trial comparing early parenteral nutrition (PN) in critically ill adults with relative contraindications to early enteral nutrition (EN)(n=686) with standard care (n=686).  Of 682 patients receiving standard care, 199 patients (29.2%) initially commenced EN, 186 patients (27.3%) initially commenced PN, and 278 patients (40.8%) remained unfed. Time to EN or PN in patients receiving standard care was 2.8 days (95% CI, 2.3 to 3.4). Patients receiving early PN commenced PN a mean of 44 minutes after enrollment (95% CI 36 to 55). There was no difference in 60 day mortality (standard care 22.8% versus early PN 21.5%; risk difference −1.26%; 95% CI −6.6 to 4.1; P = 0.60). Early PN patients rated 60 day quality of life (RAND-36 General Health Status) statistically, but not clinically meaningfully, higher (45.5 for standard care versus 49.8 for early PN; mean difference 4.3; 95% CI 0.95 to 7.58; P = 0.01). Early PN patients required fewer days of invasive ventilation (7.73 vs 7.26 days per 10 patient × ICU days, risk difference −0.47; 95% CI, −0.82 to −0.11; P = 0.01) and, based on Subjective Global Assessment, experienced less muscle wasting (0.43 vs 0.27 score increase per week; mean difference −0.16; 95% CI −0.28 to −0.038; P = 0.01) and fat loss (0.44 vs 0.31 score increase per week; mean difference −0.13; 95% CI −0.25 to −0.01; P = 0.04).

Full Text: Doig. Early Parenteral Nutrition in Critically Ill Patients With Short-term Relative Contraindications to Early Enteral Nutrition: A Randomized Controlled Trial. JAMA 2013;epublished May 20th   


New England Journal of Medicine:     Prone Ventilation

Guérin and colleagues performed a multicenter, prospective, randomized, controlled trial in 466 patients with severe ARDS comparing prone-positioning sessions of at least 16 hours duration (n=237) with the supine position (n=229). Severe ARDS was defined as a PaO2/Fi02 ratio less than 150 mm Hg, with an FiO2 of at least 0.6, a PEEP of at least 5 cm of water, and a tidal volume close to 6 ml per kilogram of predicted body weight. 28-day mortality was markedly lower in the prone group (16% versus 32.8%; P<0.001; hazard ratio for death 0.39, 95% CI 0.25 to 0.63). Unadjusted 90-day mortality was also lower with prone positioning (23.6% versus 41.0%; P<0.001; hazard ratio 0.44, 95% CI 0.29 to 0.67). The incidence of complications did not differ significantly between the groups, except for the incidence of cardiac arrests, which was higher in the supine group.

Full Text:  Guérin. Prone Positioning in Severe Acute Respiratory Distress Syndrome (PROSEVA). New Engl J Med 2013;epublished May 20th


New England Journal of Medicine:     Nighttime ICU Staffing

Kerlin et al undertook a 1-year randomized trial in an academic medical ICU to assess the effects of nighttime staffing with in-hospital intensivists (intervention) as compared with nighttime coverage by daytime intensivists who were available for consultation by telephone (control). 1598 patients were included in the analyses. The median Acute Physiology and Chronic Health Evaluation (APACHE) III score (in which scores range from 0 to 299, with higher scores indicating more severe illness) was 67 (interquartile range, 47 to 91), the median length of stay in the ICU was 52.7 hours (interquartile range, 29.0 to 113.4), and mortality in the ICU was 18%. Patients who were admitted on intervention days were exposed to nighttime intensivists on more nights than were patients admitted on control days (median, 100% of nights [interquartile range, 67 to 100] vs. median, 0% [interquartile range, 0 to 33]; P<0.001). Nonetheless, intensivist staffing on the night of admission did not have a significant effect on the length of stay in the ICU (rate ratio for the time to ICU discharge, 0.98; 95% CI 0.88 to 1.09; P=0.72), ICU mortality (relative risk 1.07; 95% CI 0.90 to 1.28), or any other end point. Analyses restricted to patients who were admitted at night showed similar results, as did sensitivity analyses that used different definitions of exposure and outcome.

Full Text:  Kerlin. A Randomized Trial of Nighttime Physician Staffing in an Intensive Care Unit. New Engl J Med 2013;epublished May 20th



European Journal of Anaesthesiology:     European Perioperative Bleeding Guideline


April 2013

Critical Care:     European Haemorrhage Guideline


New England Journal of Medicine:     Pharmaconutrition (REDOXS study)

Heyland and colleagues performed a blinded 2-by-2 factorial trial in 1223 critically ill adults with multiorgan failure and receiving mechanical ventilation, to receive supplements of glutamine, antioxidants (selenium, zinc, beta carotene, vitamin E, and vitamin C), both, or placebo. Supplements were started within 24 hours after admission to the ICU and were provided both intravenously and enterally. Glutamine therapy was associated with a trend toward increased mortality at 28 days (32.4% vs. 27.2%; adjusted odds ratio, 1.28; 95% CI 1.00 - 1.64; p=0.05) and with increased in-hospital (37.2% versus 31.0, p=0.02) and 6 month mortality (43.7% versus 37.2%, p=0.02). Antioxidants had no effect on 28-day mortality (anti-oxidants 30.8%, versus no anti-oxidants 28.8%; adjusted odds ratio, 1.09; 95% CI 0.86 - 1.40; p=0.48) or any other secondary end point. There were no differences among the groups with respect to serious adverse events (P=0.83).

Abstract:  Heyland. A Randomized Trial of Glutamine and Antioxidants in Critically Ill Patients (REDOXS study). N Engl J Med 2013;368:1489-1497


PLoS Medicine:     Bicarbonate for Kidney Injury Prevention

Haase et al performed a multicenter, double-blind, randomized controlled trial in 350 adult patients undergoing open heart surgery with the use of cardiopulmonary bypass, comparing 24 hours of intravenous infusion of sodium bicarbonate (n=174, 5.1 mmol/kg) or sodium chloride (n=176, 5.1 mmol/kg) on the incidence of post-operative acute kidney injury. Secondary endpoints included the magnitude of acute tubular damage as measured by urinary neutrophil gelatinase-associated lipocalin (NGAL), initiation of acute renal replacement therapy, and mortality. The study was stopped early due to a likely lack of efficacy and possible harm. At baseline, a greater proportion of patients in the sodium bicarbonate group presented with preoperative chronic kidney disease compared to control (38% versus 25%; p = 0.009). Sodium bicarbonate therapy was associated with a higher incidence of AKI (47.7% versus 36.4%, odds ratio 1.60, 95% CI 1.04–2.45; unadjusted p = 0.032). After multivariable adjustment, a non-significant unfavorable group difference affecting patients receiving sodium bicarbonate was found for the primary endpoint (OR 1.45 [0.90–2.33], p = 0.120]). A greater postoperative increase in urinary NGAL in patients receiving bicarbonate infusion was observed compared to control patients (p = 0.011). The incidence of postoperative renal replacement therapy was similar but hospital mortality was increased in patients receiving sodium bicarbonate compared with control (6.3% versus 1.7%, OR 3.89 [1.07–14.2], p = 0.031).

Full Text:  Haase. Prophylactic Perioperative Sodium Bicarbonate to Prevent Acute Kidney Injury Following Open Heart Surgery: A Multicenter Double-Blinded Randomized Controlled Trial. PLoS Med 2013;10(4):e1001426


Intensive Care Medicine:     Sedation

Shehabi et al conducted a multicentre prospective longitudinal cohort study in 259 patients sedated and mechanically ventilated ≥24 h. Midazolam was the main sedative prescribed. Adjusted multivariable Cox proportional hazard regression analysis showed that early deep sedation was independently associated with longer time to extubation (hazard ratio 0.93, 95% CI 0.89–0.97, p=0.003), increased hospital mortality (HR 1.11, 95 % CI 1.05–1.18, P < 0.001) and increased 180-day mortality (HR 1.09, 95 % CI 1.04–1.15, P = 0.002), but not time to delirium (HR 0.98, P = 0.23). Delirium occurred in 114 (44 %) of patients.

Full Text:  Shehabi. Sedation depth and long-term mortality in mechanically ventilated critically ill adults: a prospective longitudinal multicentre cohort study (SPICE study). Intensive Care Med 2013;39(5):910-918


Critical Care Medicine:     Outcomes post ICU

In a cohort study of 91,203 Dutch ICU survivors discharged alive from hospital, the mortality risk at 1, 2, and 3 years was 12.5%, 19.3%, and 27.5%, respectively. The 3-year mortality after hospital discharge in ICU patients was higher than the weighted average of the gender and age-specific death risks of the general Dutch population (27.5% versus 8.2%). In comparison with general ICU patients, elective and cardiac surgical patients had lower adjusted hazard ratios for mortality (0.73 and 0.28, respectively), while medical and cancer patients had higher adjusted hazard ratios for mortality (1.41, 1.94, respectively).

Abstract:  Brinkman. Mortality After Hospital Discharge in ICU Patients. Crit Care Med 2013;41(5):1229-1236


Mayo Clinic Proceedings:     L-Carnitine in Acute Myocardial Infarction

DiNicolantonio and colleagues completed a systematic review and meta-analysis (13 controlled trials, n=3629) to evaluate the effects of L-carnitine in the setting of acute myocardial infarction.
This intervention was associated with reductions in all-cause mortality (odds ratio 0.73; 95% CI 0.54-0.99; p=0.05; risk ratio 0.78; 95% CI 0.60-1.00; p=.005), incidence of ventricular arrthymias (RR 0.35; 95% CI 0.21-0.58; P<.0001), and development of angina (RR 0.60; 95% CI 0.50-0.72; p<.00001), with no reduction in the development of heart failure (RR 0.85; 95% CI 0.67-1.09; p=0.21) or myocardial reinfarction (RR 0.78; 95% CI 0.41-1.48; p=0.45).

Full Text:  DiNicolantonio. L-carnitine in the secondary prevention of cardiovascular disease: Systematic review and meta-analysis. Mayo Clin Proc 2013;epublished April 12th


New England Journal of Medicine:     H7N9

Full Text:  Gao. Human Infection with a Novel Avian-Origin Influenza A (H7N9) Virus. N Eng J Med 2013; epublished April 11th

Commentary: Uyeki. Global Concerns Regarding Novel Influenza A (H7N9) Virus Infections. N Eng J Med 2013; epublished April 11th


Lancet Infectious Disease:     Selective Digestive Decontamination

Daneman et al performed a systematic review (64 studies) of the effect of selective digestive decontamination (SDD) or selective oropharyngeal decontamination (SOD) on the rates of colonisation or infection with antimicrobial-resistant pathogens in critically ill patients. Comparing patients who received SDD or SOD versus controls who received no intervention, there was no difference in the prevalence of colonisation or infection with Gram-positive antimicrobial-resistant pathogens of interest, including meticillin-resistant Staphylococcus aureus (odds ratio 1·46, 95% CI 0·90—2·37) and vancomycin-resistant enterococci (0·63, 0·39—1·02). Among Gram-negative bacilli, there was no difference in aminoglycoside-resistance (0·73, 0·51—1·05) or fluoroquinolone-resistance (0·52, 0·16—1·68), but there was a reduction in polymyxin-resistant Gram-negative bacilli (0·58, 0·46—0·72) and third-generation cephalosporin-resistant Gram-negative bacilli (0·33, 0·20—0·52) in recipients of selective decontamination compared with those who received no intervention. Conclusion: SDD or SOD was not associated with the development of resistant pathogens in ICU patients, although the effect of decontamination on ICU-level antimicrobial resistance rates is understudied.

Abstract:  Daneman. Effect of selective decontamination on antimicrobial resistance in intensive care units: a systematic review and meta-analysis. Lancet Infectious Diseases 2013;13(4):328-341


Lancet:     Chlorhexidine Bathing for Children

Milstone and colleagues performed an unmasked, cluster-randomised, two-period crossover trial in 4947 children comparing a daily bathing routine of either standard bathing practices or using a cloth impregnated with 2% chlorhexidine gluconate CHG, for a 6-month period. Units switched to the alternative bathing method for a second 6-month period. Although there was no difference in the intention-to-treat analysis (chlorhexidine bathing: 3·52 per 1000 days, 95% CI 2·64—4·61 versus standard bathing: 4·93 per 1000 days, 3·91—6·15; adjusted incidence rate ratio 0·71, 95% CI 0·42—1·20), in the per protocol analysis, there was a reduced incidence of bacteraemia in those receiving chlorhexidine bathing (3·28 per 1000 days, 2·27—4·58 versus standard bathing: 4·93 per 1000 days, 3·91—6·15; adjusted incidence rate ratio 0·64, 0·42—0·98). No serious study-related adverse events were recorded, and the incidence of CHG-associated skin reactions was 1·2 per 1000 days (95% CI 0·60—2·02).  Conclusion: Compared with standard daily bathing, chlorhexidine daily bathing was associated with a lower incidence of bacteraemias.

Abstract:  Milstone. Daily chlorhexidine bathing to reduce bacteraemia in critically ill children: a multicentre, cluster-randomised, crossover trial. Lancet 2013;381(9872):1099-1106


March 2013

Intensive Care Medicine:     Tetrastarch

Patel and colleagues performed a systematic review and meta-analysis to assess the effect of fluid resuscitation with 6% tetrastarch in comparison with other non-HES fluids in adults with severe sepsis. Six randomized controlled trials (n=3,033) were included, with a median tetrastarch dose of 37 ml/kg. In comparison with crystalloids, there was a 13% relative increase in 90 day mortality (RR 1.13; 95% CI 1.02-1.25; p=0.02), with a number needed to harm of 28.8 (95% CI 14.6–942.5).Tetrastarch exposure was also associated with renal replacement therapy (p = 0.01; NNH 15.7) and allogeneic transfusion support (p = 0.001; NNH 9.9). Conclusion: Fluid resuscitation with 6% tetrastarch is associated with increased mortality, need for renal replacement therapy and red cell transfusion in adults with severe sepsis.

Abstract: Patel. Randomised trials of 6% tetrastarch (hydroxyethyl starch 130/0.4 or 0.42) for severe sepsis reporting mortality: systematic review and meta-analysis. Intensive Care Med 2013;epublished ahead of print


American Journal of Respiratory and Critical Care Medicine:     Sepsis-Induced Organ Failure

To evaluate the degree of sepsis-induced cardiomyocyte and renal tubular cell injury and death, using light and electron microscopy and immunohistochemical staining for markers of cellular injury and stress, Takasu and colleagues compared rapid postmortem cardiac and renal analysis in 44 septic patients with control hearts from 12 transplant and 13 brain-dead patients and control kidneys from 20 trauma patients and 8 patients with cancer. They determined cell death is rare in sepsis-induced cardiac dysfunction, but cardiomyocyte injury occurs. Renal tubular injury is common in sepsis but presents focally; most renal tubular cells appear normal. Conclusion: In sepsis, the degree of cell injury and death does not account for severity of organ dysfunction.

Abstract:  Takasu. Mechanisms of Cardiac and Renal Dysfunction in Patients Dying of Sepsis. Am J Respir Crit Care Med. 2013;187:509-517


Critical Care:     Diabetic Glycaemic Control

Krinsley et al completed a retrospective study of 44,964 patients admitted to 23 intensive care units (ICU's) from 9 countries, between February, 2001 and May, 2012 to analyze the independent association of blood glucose with mortality. In non-diabetic patients, mean blood glucose between 80-140 mg/dL was independently associated with reduced mortality and mean blood glucose greater than 140 mg/dL with increased mortality. In diabetics, mean blood glucose of 80-110 mg/dL was associated with increased mortality and mean blood glucose of 10-180 mg/dL with decreased risk of mortality. Hypoglycemia (blood glucose < 70 mg/dL) was independently associated with increased risk of mortality among both diabetics and non-diabetics. Increased glycemic variability, defined as a coefficient of variability greater than 20%, was independently associated with increased mortality in non-diabetics. Derangements of more than 1 domain of glycemic control had a cumulative association with mortality, especially for patients without diabetes. Conclusion: In a large retrospective study, dysglycaemia is associated with increased mortality in the critically ill; diabetics may benefit from a higher blood glucose level.


Cochrane Review:     Colloids versus Crystalloids for Fluid Resuscitation

In an updated systematic review and meta analysis, Perel and colleagues compared crystalloids with colloids for fluid resuscitation in the critically ill.

Colloids compared to crystalloids:Albumin or plasma protein fraction - 24 trials reported data on mortality, including a total of 9920 patients. The pooled risk ratio (RR) from these trials was 1.01 (95% confidence interval (CI) 0.93 to 1.10). When we excluded the trial with poor-quality allocation concealment, pooled RR was 1.00 (95% CI 0.92 to 1.09).

Hydroxyethyl starch: 25 trials compared hydroxyethyl starch with crystalloids and included 9147 patients. The pooled RR was 1.10 (95% CI 1.02 to 1.19).

Modified gelatin: 11 trials compared modified gelatin with crystalloid and included 506 patients. The pooled RR was 0.91 (95% CI 0.49 to 1.72). (When the trials by Boldt et al were removed from the three preceding analyses, the results were unchanged.) Dextran - nine trials compared dextran with a crystalloid and included 834 patients. The pooled RR was 1.24 (95% CI 0.94 to 1.65).

Colloids in hypertonic crystalloid compared to isotonic crystalloid:  Nine trials compared dextran in hypertonic crystalloid with isotonic crystalloid, including 1985 randomised participants. Pooled RR for mortality was 0.91 (95% CI 0.71 to 1.06).

Conclusion:  The authors conclude that as colloids are more expensive than crystalloids, offer no benefit over crystalloids, and hydroxyethyl starches are associated with increased mortality, the ongoing clinical use of colloids is difficult to justify.

Perel. Colloids versus crystalloids for fluid resuscitation in critically ill patients. Cochrane Database of Systematic Reviews 2013;2:CD000567


Cochrane Review:     Pulmonary Artery Catheters

Rajaram et al performed a systematic review and meta analysis, including 13 studies (n=5686), comparing management with and without a pulmonary artery catheter in critically ill adults. The pooled risk ratio (RR) for mortality for 5 studies of general intensive care patients was 1.02 (95% CI 0.96 - 1.09) and for 8 studies of high-risk surgery patients the RR was 0.98 (95% CI 0.74 to 1.29). In 5 of the studies in high-risk surgery patients which evaluated the effectiveness of pre-operative optimization, there was no difference in mortality. PAC did not affect general ICU length of stay (reported by four studies) or hospital length of stay (reported by nine studies). Four studies, conducted in the United States (US), reported costs based on hospital charges billed, which on average were higher in the PAC groups. Two of these studies qualified for analysis and did not show a statistically significant hospital cost difference (mean difference USD 900, 95% CI -2620 to 4420, P = 0.62). Conclusion:  The use of a pulmonary artery catheter was not associated with decreased mortality, general ICU or hospital length of stay, or cost for adult patients in intensive care; although whether this is due to the monitor or therapeutic strategy employed is unclear.

Full Text: Rajaram. Pulmonary artery catheters for adult patients in intensive care. Cochrane Database Syst Rev. 2013 Feb 28;2:CD003408


Cochrane Review:     High-Frequency Oscillation

In an "updated" review (although already outdated as it was performed in 2011, before the recent OSCAR and OSCILLATE trials were reported, but only published now), Sud and colleagues determined in 8 randomized controlled trials (n=433) that high frequency oscillation was a promising treatment for ALI and ARDS prior to the uptake of current lung protective ventilation strategies. Conclusion: This meta analysis is outdated and the results obsolete.

Full Text:  Sud. High-frequency ventilation versus conventional ventilation for treatment of acute lung injury and acute respiratory distress syndrome. Cochrane Database Syst Rev 2013 Feb 28;2:CD004085


Cochrane Review:     Lung Protective Ventilation

In an updated review (no new data found) Petrucci and colleagues performed a systematic review and meta analysis (six trials, n = 1297) comparing protective ventilation with non-protectice ventilation in ALI/ARDS.  Lung-protective ventilation was associated with a 26% relative decrease in mortality at 28 days (95% CI 0.61 - 0.88) and a 20% relative decrease in hospital mortality (95% CI 0.69 - 0.92). Overall mortality was not significantly different if a plateau pressure less than or equal to 31 cm H2O in the control group was used (RR 1.13, 95% CI 0.88 - 1.45). There was insufficient evidence for morbidity and long-term outcomes. Conclusion: Lung-protective ventilation is associated with significant improvements in mortality and length of hospital stay in ALI/ARDS patients.

Full Text:  Petrucci. Lung protective ventilation strategy for the acute respiratory distress syndrome. Cochrane Database Syst Rev 2013 Feb 28;2:CD003844


February 2013

Intensive Care Medicine:     Renal Replacement Therapy

Schneider and colleagues undertook a systematic review and meta analysis to compare the rate of dialysis dependence among severe acute kidney injury survivors according whether continuous renal replacement therapy (CRRT) or intermittent haemodialysis (IHD) was the initial mode of renal replacement therapy. 23 studies were identified: seven randomized controlled trials (RCTs) and 16 observational studies involving 472 and 3,499 survivors, respectively. Pooled analyses of RCTs showed no difference in the rate of dialysis dependence among survivors (relative risk, RR 1.15 [95 % CI 0.78–1.68], I2 = 0 %). However, pooled analyses of observational studies suggested a higher rate of dialysis dependence among survivors who initially received IHD as compared with CRRT (RR 1.99 [95 % CI 1.53–2.59], I2 = 42 %). Conclusion: Observational, but not interventional, data suggests initial IHD therapy may be associated with prolonged dependence on renal replacement therapy.

Abstract:  Schneider. Choice of renal replacement therapy modality and dialysis dependence after acute kidney injury: a systematic review and meta-analysis. Intensive Care Med 2013;epublished February 27th


New England Journal of Medicine:     Dabigatran

In two double-blind, randomized trials, dabigatran (150 mg twice daily) was compared with warfarin (active-control study) or with placebo (placebo-control study) in patients with venous thromboembolism who had completed at least 3 initial months of therapy. In the active-control study, for rates of recurrent venous thromboembolism, dabigatran (1.8%; 26/1430) was not inferior to warfarin (1.3%; 18/1426) (hazard ratio with dabigatran, 1.44; 95% CI 0.78-2.64; P=0.01 for noninferiority). Similarly, there was no difference in major bleeding; dabigatran group (0.9%, 13/1430) versus warfarin group (1.8%; 25/1426) (hazard ratio 0.52; 95% CI 0.27-1.02), although major or clinically relevant bleeding was less frequent with dabigatran (HR 0.54; 95% CI 0.41-0.71). Acute coronary syndromes were more common in the dabigatran group (0.9%; 13/1430) versus (0.2%; 3/1426) (P=0.02). In the placebo-control study, recurrent venous thromboembolism was less common in the dabigatran group (0.4%; 3/681) than in the placebo group (5.6%; 37/662) (HR 0.08; 95% CI 0.02-0.25; P<0.001). Major or clinically relevant bleeding occurred more frequently in the dabigatran group (5.3%; 36/681) versus (1.8%; 12/662) (HR 2.92; 95% CI 1.52 to 5.60). Acute coronary syndromes occurred in 1 patient each in the dabigatran and placebo groups. Conclusion:  Dabigatran was not inferior to warfarin for the extended treatment of venous thromboembolism and carried a lower risk of major or clinically relevant bleeding than warfarin but a higher risk than placebo.

Abstract:  Schulman. Extended Use of Dabigatran, Warfarin, or Placebo in Venous Thromboembolism (RE-MEDY and the RE-SONATE Trials). N Engl J Med 2013;368:709-718


New England Journal of Medicine:     Apixiban

Agnelli et al completed a randomized, double-blind study, comparing two doses of apixaban (2.5 mg and 5 mg, twice daily for 12 months) with placebo in 2486 patients with venous thromboembolism who had completed 6 to 12 months of anticoagulation therapy. Symptomatic recurrent venous thromboembolism or death from venous thromboembolism occurred in 8.8% (73/829) in those receiving placebo, 1.7% (14/840) in those receiving apixaban 2.5 mg (a difference of 7.2%; 95% CI 5.0 to 9.3) and 1.7% (14/813) in those receiving 5 mg of apixaban (a difference of 7.0%; 95% CI, 4.9 to 9.1) (P<0.001 for both comparisons). The rates of major bleeding were 0.5% in the placebo group, 0.2% in the 2.5-mg apixaban group, and 0.1% in the 5-mg apixaban group. The rates of clinically relevant nonmajor bleeding were 2.3% in the placebo group, 3.0% in the 2.5-mg apixaban group, and 4.2% in the 5-mg apixaban group. The rate of death from any cause was 1.7% in the placebo group, as compared with 0.8% in the 2.5-mg apixaban group and 0.5% in the 5-mg apixaban group. Conclusions:  Extended anticoagulation with apixaban, at either a treatment dose (5 mg) or a thromboprophylactic dose (2.5 mg), reduced the risk of recurrent venous thromboembolism without increasing the rate of major bleeding.

Abstract:  Agnelli. Apixaban for Extended Treatment of Venous Thromboembolism (AMPLIFY-EXT study). N Engl J Med


The Lancet:     Coronary Revascularization

Mohr et al report the 5-year results of the multi-centre, randomized SYNTAX trial, which compared coronary artery bypass graft surgery (CABG) with percutaneous coronary intervention (PCI) for the treatment of patients with left main coronary disease or three-vessel disease. 1800 patients were randomly assigned to CABG (n=897) or PCI (n=903). Kaplan-Meier estimates of the major endpoint, a composite rate of major adverse cardiac and cerebrovascular events (MACCE), were higher in the PCI group (37.3 versus 26·9%, p<0·0001). Likewise, estimates of myocardial infarction ( 9·7% versus 3·8%; p<0·0001) and repeat revascularisation (25·9% versus 13·7% vs ; p<0·0001) were significantly increased with PCI versus CABG. Neither all-cause death (PCI group 13·9% versus CABG group 11·4%; p=0·10) nor stroke (PCI group 2.4% versus CABG group 3·7%; p=0·09) were  significantly different. In patients with intermediate or high SYNTAX scores, MACCE was significantly increased with PCI (intermediate score, PCI group 36·0% versus CABG group 25·8%, p=0·008; high score, PCI group 44·0% versus CABG group 26·8%; p<0·0001). Conclusion: CABG is superior to PCI for complex lesions (high or intermediate SYNTAX scores), although for less complex disease (low SYNTAX scores) or left main coronary disease (low or intermediate SYNTAX scores), PCI is an acceptable alternative.

Abstract:  Mohr. Coronary artery bypass graft surgery versus percutaneous coronary intervention in patients with three-vessel disease and left main coronary disease: 5-year follow-up of the randomised, clinical SYNTAX trial. Lancet 2013;381(9867):629-638


Critical Care Medicine:     Lactoferrin in Sepsis

Guntupalli et al completed a prospective, randomized, double-blind, placebo-controlled, multicenter phase 2 trial, investigating whether enteral lactoferrin (talactoferrin), a glycoprotein with anti-infective and anti-inflammatory properties which contributes to gastrointestinal mucosal barrier integrity, could reduce 28-day all-cause mortality in 194 patients with severe sepsis. The all-cause mortality at 28 days was 26.9% in the placebo group and 14.4% in the talactoferrin group (two-sided p = 0.052), representing a 12.5% absolute and a 46.5% relative reduction in mortality, meeting the protocol-specified primary endpoint. Reduction in all cause mortality was sustained at 6 months (p = 0.039). These reductions in mortality were observed across a wide spectrum of subgroups. The drug was well tolerated with a safety profile similar to that of placebo. Conclusion: Enteral administration of talactoferrin reduced 28-day all-cause mortality in patients with severe sepsis.

Abstract:  Guntupalli. A Phase 2 Randomized, Double-Blind, Placebo–Controlled Study of the Safety and Efficacy of Talactoferrin in Patients With Severe Sepsis. Critical Care Medicine 2013;41(3):706-716


JACC Cardiovascular Interventions:     PCI post Acute Myocardial Infarction with Cardiac Arrest

Mylotte et al conducted a multicenter prospective observational study to assess the impact of multivessel (MV) primary percutaneous coronary intervention (PCI) on clinical outcomes in 266 patients with ST-segment elevation myocardial infarction (STEMI) presenting with cardiogenic shock and resuscitated cardiac arrest.Patients with single vessel disease (SVD, 36.5%) had increased 6-month survival compared to those with multi-vessel disease (MVD, 29.6% vs. 42.3%, p = 0.032). Baseline characteristics were similar in those with MVD undergoing culprit-only (60.9%) or MV (39.1%) primary PCI. However, 6-month survival was significantly greater in patients who underwent MV PCI (43.9% vs. 20.4%, p = 0.0017). This survival advantage was mediated by a reduction in the composite of recurrent cardiac arrest and death due to shock (p = 0.024) in MV PCI patients. In those with MVD, culprit artery PCI success (hazard ratio 0.63; 95% CI 0.41 to 0.96, p = 0.030) and MV primary PCI (HR 0.57; 95% CI: 0.38 to 0.84, p = 0.005) were associated with increased 6-month survival.  Conclusion:  Multivessel primary PCI may improve  outcomes in patients with STEMI and multivessel disease presenting with cardiogenic shock and cardiac arrest.

Full Text:  Mylotte. Primary Percutaneous Coronary Intervention in Patients With Acute Myocardial Infarction, Resuscitated Cardiac Arrest, and Cardiogenic ShockThe Role of Primary Multivessel Revascularization. J Am Coll Cardiol Intv 2013;6(2):115-125


Journal of the American Medical Association:     Hydroxyethyl Starch

To evaluate the association of hydroxyethyl starch use with mortality and acute kidney injury, Zarychanski and colleagues performed a systematic review and meta analysis (initially 38 trials with 10,880 patients, refined to 31 trials with 10,290 after the exclusion of retracted trials) comparing hydroxyethyl starch to crystalloids, albumin, or gelatin. The majority of trials were categorized as having an unclear risk or high risk of bias. Excluding the retracted studies, hydroxyethyl starch was associated with increased mortality (relative risk 1.09; 95% CI 1.02 to 1.17; I2 0%; absolute risk 1.51%; 95% CI 0.02% to 3.00%), increased renal failure among 8725 patients (RR 1.27; 95% CI 1.09 to 1.47; I2 26%; AR 5.45%; 95% CI 0.44% to 10.47%), and increased use of renal replacement therapy among 9258 patients (RR 1.32; 95% CI 1.15 to 1.50; I2 0%; AR 3.12%; 95% CI 0.47% to 5.78%). Conclusion: In a systematic review and meta analysis, hydroxyethyl starch administration was associated with increased risks of death, renal failure and renal replacement therapy.

Abstract: Zarychanski. Association of Hydroxyethyl Starch Administration With Mortality and Acute Kidney Injury in Critically Ill Patients Requiring Volume Resuscitation: A Systematic Review and Meta-analysis. JAMA 2013;309(7):678


British Medical Journal:     Hydroxyethyl Starch

Haase et al completed a systematic review and meta analysis in 9 trials and 3456 patients, to assess the effects of fluid therapy with hydroxyethyl starch 130/0.38-0.45 versus crystalloid or albumin on mortality, kidney injury, bleeding, and serious adverse events in patients with sepsis. Hydroxyethyl starch 130/0.38-0.45 versus crystalloid or albumin did not affect the relative risk of death (1.04, 95% CI 0.89 to 1.22, 3414 patients, eight trials), but in the predefined analysis of trials with low risk of bias the relative risk of death was 1.11 (1.00 to 1.23, trial sequential analysis (TSA) adjusted 95% CI 0.95 to 1.29, 3016 patients, four trials). In the hydroxyethyl starch group, renal replacement therapy was used more (1.36, 1.08 to 1.72, TSA adjusted 1.03 to 1.80, 1311 patients, five trials), and the relative risk of acute kidney injury was 1.18 (0.99 to 1.40, TSA adjusted 0.90 to 1.54, 994 patients, four trials). More patients in the hydroxyethyl starch group were transfused with red blood cells (1.29, 1.13 to 1.48, TSA adjusted 1.10 to 1.51, 973 patients, three trials), and more patients had serious adverse events (1.30, 1.02 to 1.67, TSA adjusted 0.93 to 1.83, 1069 patients, four trials). The transfused volume of red blood cells did not differ between the groups (mean difference 65 mL, 95% CI −20 to 149 mL, three trials). Conclusion: In sepsis, the use of hydroxyethyl starch 130/0.38-0.45, versus crystalloid or albumin, was associated with increased use of renal replacement therapy, increased red cell transfusion, and more serious adverse events.

Full Text: Haase. Hydroxyethyl starch 130/0.38-0.45 versus crystalloid or albumin in patients with sepsis: systematic review with meta-analysis and trial sequential analysis. BMJ 2013;346:f839


Critical Care:     ECMO

Zangrillo and colleagues completed a systematic review and meta analysis, including 8 studies and 1357 patients, to describe the use of extracorporeal membrane oxygenation (ECMO, n=266, 20%) in severe acute lung injury due to confirmed or suspected H1N1 infection.  Patients had a median SOFA score of 9, and had received mechanical ventilation before ECMO implementation for a median of 2 days. ECMO was implanted before inter-hospital patient transfer in 72% of cases and in most patients (94%) the veno-venous configuration was used. ECMO was maintained for a median of 10 days. Outcomes were highly variable among the included studies, with in-hospital or short-term mortality ranging between 8% and 65%, mainly depending on baseline patient features. Random-effect pooled estimates suggested an overall in-hospital mortality of 28% (95% CI 18%-37%; I2=64%).

Full Text:  Zangrillo. Extracorporeal membrane oxygenation (ECMO) in patients with H1N1 influenza infection: a systematic review and meta-analysis including 8 studies and 266 patients receiving ECMO. Crit Care. 2013 Feb 13;17(1):R30


Intensive Care Medicine:     Hydroxyethyl Starch

Gattas and colleagues undertook a systematic review and meta analysis of 35 trials and 10,391 patients to compare outcomes between acutely ill adults fluid resuscitated with 6 % hydroxyethyl starch (6% HES 130/0.4) or other resuscitation fluids.  The mortality rate not-significantly higher (HES:19.8%,  928/4,691 versus control: 18.5%, 871/4,720; relative risk with HES 1.08, 95 % CI: 1.00 to 1.17, I 2 = 0 %). Renal replacement therapy occurred more often with HES therapy (HES: 8.9%, 378/4,236 versus control: 7.2%,  306/4,260;; relative risk with HES 1.25, 95 % CI 1.08 to 1.44, I 2 = 0 %). Conclusion: Fluid resuscitation with 6% HES 130/0.4 is associated with an increased risk of RRT, and with a strong signal of increaed mortality.

Abstract:  Gattas. Fluid resuscitation with 6 % hydroxyethyl starch (130/0.4 and 130/0.42) in acutely ill patients: systematic review of effects on mortality and treatment with renal replacement therapy. Intensive Care Med 2013;epublished Febuary 14th


Journal of the American Medical Association:     Tedizolid - a new gram positive antimicrobial

Prokocimer and colleagues undertook an international phase 3, randomized, double-blind, noninferiority trial in 667 patients with acute bacterial skin and skin structure infections to establish the noninferiority of tedizolid phosphate (200 mg orally once daily for 6 days, n=332) versus linezolid (600mg orally 12 hourly for 10 days, n=335).  In intent-to-treat analysis, there was no difference in early clinical treatment response rates: tedizolid 79.5% (95% CI 74.8% to 83.7%) versus linezolid 79.4% (95% CI 74.7% to 83.6%); a treatment difference of 0.1%, (95% CI, −6.1% to 6.2%). The sustained day 11 clinical treatment response rates at the end of treatment were also not different: tedizolid 69.3% (95% CI, 64.0% to 74.2%) versus linezolid 71.9% (95% CI, 66.8% to 76.7%); a treatment difference of −2.6%, 95% CI, −9.6% to 4.2%). Similarly, ther were no differences in investigator-assessed clinical treatment success rates at a posttherapy evaluation visit: tedizolid  85.5% (95% CI, 81.3% to 89.1%) versus linezolid 86.0% (95% CI, 81.8% to 89.5%) (a treatment difference of −0.5%, 95% CI, −5.8% to 4.9%, and were similar for 178 patients with methicillin-resistant Staphylococcus aureus isolated from the primary lesion. Conclusions:. Tedizolid phosphate was not inferior to linezolid for treating acute bacterial skin and skin structure infections.

Abstract:  Prokocimer. Tedizolid Phosphate vs Linezolid for Treatment of Acute Bacterial Skin and Skin Structure Infections. The ESTABLISH-1 Randomized Trial. JAMA 2013;309(6):559-569


New England Journal of Medicine:     Rivaroxaban

To determine the appropriate duration of thromboprophylaxis in hospitalized patients with acute medical illnesses, Cohen et al completed a multicenter, randomized, double-blind trial in 8101 patients, comparing, (I think, it's remarkably poorly described) (1) early enoxaparin with early rivaroxaban, and (2) follow-on oral placebo in those who received enoxaparin versus extended duration rivaroxaban. Venous thromboembolism occurred in 78 of 2938 patients (2.7%) receiving rivaroxaban and 82 of 2993 patients (2.7%) receiving enoxaparin at day 10 (relative risk with rivaroxaban, 0.97; 95% CI 0.71 to 1.31; P=0.003 for noninferiority) and in 131 of 2967 patients (4.4%) who received rivaroxaban and 175 of 3057 patients (5.7%) who received enoxaparin followed by placebo at day 35 (relative risk, 0.77; 95% CI, 0.62 to 0.96; P=0.02). A principal safety outcome event occurred in 111 of 3997 patients (2.8%) in the rivaroxaban group and 49 of 4001 patients (1.2%) in the enoxaparin group at day 10 (P<0.001) and in 164 patients (4.1%) and 67 patients (1.7%) in the respective groups at day 35 (P<0.001). Conclusion: In acutely ill medical patients, rivaroxaban was (1) noninferior to enoxaparin for standard-duration thromboprophylaxis; (2) extended-duration rivaroxaban reduced the risk of venous thromboembolism, although (3) rivaroxaban was associated with an increased risk of bleeding.

Abstract:  Cohen. Rivaroxaban for Thromboprophylaxis in Acutely Ill Medical Patients (MAGELLAN study). N Engl J Med 2013; 368:513-523

New England Journal of Medicine:     Chlorhexidine for Infection Prevention

Climo and colleagues performed a multicenter, cluster-randomized, nonblinded crossover trial in 7727 patients, comparing daily bathing with 2% chlorhexidine-impregnated washcloths with non-antimicrobial washcloths on the acquisition of multidrug-resistant organisms and the incidence of hospital-acquired bloodstream infections. The overall rate of multidrug-resistant organisms acquisition was 23% lower rate with chlorhexidine bathing (5.10 cases per 1000 patient-days versus 6.60 cases per 1000 patient-days; P=0.03). Similarly, the overall rate of hospital-acquired bloodstream infections was 28% lower rate with chlorhexidine-impregnated washcloths (4.78 cases per 1000 patient-days versus 6.60 cases per 1000 patient-days, P=0.007). No serious skin reactions were noted. Conclusion: Compared with standard non-antimicrobial washing, washing with 2% chlorhexidine was associated with lower rates of acquisition of multidrug-resistant organisms and lower incidence of hospital-acquired bloodstream infections.

Abstract:  Climo. Effect of Daily Chlorhexidine Bathing on Hospital-Acquired Infection. N Engl J Med 2013;368:533-542


New England Journal of Medicine:     Stroke

In patients with moderate-to-severe acute ischemic stroke who received intravenous t-PA within 3 hours after symptom onset, Broderick et al randomly assigned eligible patients to receive additional endovascular therapy or not, in a 2:1 ratio. The study was stopped early because of futility after 656 participants had undergone randomization. The proportion of participants with a modified Rankin score of 2 or less (indicating functional independence) at 90 days did not differ significantly according to treatment (40.8% with endovascular therapy and 38.7% with intravenous t-PA alone; absolute adjusted difference, 1.5 % points; 95% CI 6.1 to 9.1). Mortality was unchanged at 90 days ( endovascular-therapy: 19.1% versus intravenous t-PA 21.6%; P=0.52), as was the proportion of patients with symptomatic intracerebral hemorrhage within 30 hours after initiation of t-PA (6.2% and 5.9%, respectively; P=0.83). Also, there were there no significant differences for the predefined subgroups of patients with an NIHSS score of >20 or <20. Conclusion: Additional endovascular therapy after intravenous t-PA was not associated with improved outcomes in acute ischaemic stroke.

Full Text:  Broderick. Endovascular Therapy after Intravenous t-PA versus t-PA Alone for Stroke (IMS III trial). N Eng J Med 2013;epublished February 7th


Ciccone et al performed a controlled trial in 362 patients with acute ischemic stroke, randomized within 4.5 hours after onset to endovascular therapy (intraarterial thrombolysis with recombinant tissue plasminogen activator [t-PA], mechanical clot disruption or retrieval, or a combination of these approaches, n=181) or intravenous t-PA (n=181). The median time from stroke onset to the start of treatment was shorter for endovascular therapy than for intravenous t-PA (3.75 hours versus 2.75 hours, P<0.001). At 3 months, 55 patients in the endovascular-therapy group (30.4%) and 63 in the intravenous t-PA group (34.8%) were alive without disability (odds ratio adjusted for age, sex, stroke severity, and atrial fibrillation status at baseline, 0.71; 95% CI 0.44 to 1.14; P=0.16). There were no differences in fatal or nonfatal symptomatic intracranial hemorrhage within 7 days (6% each group), or in rates of other serious adverse events or the case fatality rate. Conclusion: in patients with acute ischemic stroke endovascular therapy is not superior to standard treatment with intravenous t-PA.

Full Text: Ciccone. Endovascular Treatment for Acute Ischemic Stroke (SYNTHESIS Expansion trial). N Eng J Med 2013;epublished February 6th


Kidwell and colleagues completed a randomized controlled trial in 118 patients within 8 hours after the onset of large-vessel, anterior-circulation strokes, comparing mechanical embolectomy  or receive standard care. Revascularization in the embolectomy group was achieved in 67% of the patients. Ninety-day mortality was 21%, and the rate of symptomatic intracranial hemorrhage was 4%; neither rate differed across groups. Among all patients, mean scores on the modified Rankin scale did not differ between embolectomy and standard care (3.9 vs. 3.9, P=0.99). Embolectomy was not superior to standard care in patients with either a favorable penumbral pattern (mean score, 3.9 vs. 3.4; P=0.23) or a nonpenumbral pattern (mean score, 4.0 vs. 4.4; P=0.32). In the primary analysis of scores on the 90-day modified Rankin scale, there was no interaction between the pretreatment imaging pattern and treatment assignment (P=0.14). Conclusion: A favorable penumbral pattern on neuroimaging did not identify patients who would differentially benefit from endovascular therapy for acute ischemic stroke, nor was embolectomy shown to be superior to standard care.

Full Text:  Kidwell. A Trial of Imaging Selection and Endovascular Treatment for Ischemic Stroke (MR RESCUE study). N Eng J Med 2013;epublished February 8th


American Journal of Respiratory and Critical Care Medicine:    Berlin Definition of ARDS

Thille et al performed a retrospective study of all autopsies in their unit over a 20 year period (n=712), to evaluate the accuracy of the new Berlin Definition of ARDS for identifying the pathological findings of ARDS, diffuse alveolar damage. 356 patients had clinical criteria for ARDS at the time of death, and were classified as mild (N=49, 14%), moderate (N=141, 40%) and severe (N=166, 46%). Sensitivity was 89% and specificity 63% to identify ARDS. Diffuse alveolar damage was found in 159 of 356 (45%) patients with clinical criteria for ARDS (in 12%, 40% and 58% of mild, moderate and severe ARDS patients, respectively). Diffuse alveolar damage was more frequent in patients who met clinical criteria for ARDS during more than 72h and was found in 69% of severe ARDS ≥ 72h. Conclusion: In a retrospective study over a 20 year period, The Berlin definition for ARDS correlated reasonably well with the pathological findings of ARDS.

Abstract:  Thille. Comparison of the Berlin Definition for Acute Respiratory Distress Syndrome with Autopsy. Am J Respir Crit Care Med 2013;epublished January 31st  


American Journal of Respiratory and Critical Care Medicine:    Nutrition

In a secondary analyses of the randomized controlled EPaNIC trial (n = 4,640), Casaer and colleagues sought to determine whether the deleterious effects of early parenteral relate to severity of illness or to the dose or type of macronutrients. In no subgroup defined by type or severity of illness was a beneficial effect of early PN observed. The lowest dose of macronutrients was associated with the fastest recovery and any higher dose, administered parenterally or enterally, was associated with progressively more delayed recovery. The amount of proteins/amino acids rather than of glucose appeared to explain delayed recovery with early feeding. Conclusion: In a two-centre study comparing early or late parenteral supplementation of insufficient enteral nutrition, combined parenteral/enteral nutrition delayed recovery irrespective of severity of critical illness. No dose or type of macronutrient was found to be associated with improved outcome.

Abstract:  Casaer. Role of Disease and Macronutrient Dose in the Randomized Controlled EPaNIC Trial. Am J Respir Crit Care Med 2013;187:247-255


January 2013

American Journal of Respiratory and Critical Care Medicine:      Statins in Sepsis

To investigate the effects of statin therapy in severe sepsis, Kruger and colleagues completed a phase II, multicenter,  randomized, double-blind, placebo controlled trial, comparing atorvastatin 20mg daily (n=123) versus placebo (n=127). There was no difference in the primary end-point of IL-6 concentrations (p=0.76) or in secondary endpoints including length of stay, change in SOFA scores or mortality at ICU discharge, hospital discharge, 28 days or 90 days (15 vs. 19%) or adverse effects between the two groups. Cholesterol was lower in atorvastatin treated patients [2.4(0.07) vs. 2.6(0.06) mmol/L, p=0.006]. In the pre -defined group of 77 prior statin users, those randomised to placebo had a greater 28 day mortality (28% vs.5%, P=0.01). The difference was not statistically significant at 90 days (28 vs. 11%, p=0.06). Conclusion: Atorvastatin therapy was not associated with improvements in biological or clinical endpoints in severe sepsis.

Abstract:  Kruger. A Multicentre Randomised Trial of Atorvastatin Therapy in Intensive Care Patients with Severe Sepsis. Am J Respir Crit Care Med 2013;epublished ahead of print


Journal of the American Medical Association:     Weaning in Prolonged Ventilation

Jurban et al performed a randomized study comparing weaning duration with pressure support (n = 155) vs unassisted breathing through a tracheostomy (n = 161) in patients transferred to a single long-term acute care hospital for weaning from prolonged ventilation. Of 152 patients in the pressure-support group, 68 (44.7%) were weaned and 22 (14.5%) died. Of 160 patients in the unassisted breathing group, 85 (53.1%) were weaned and 16 (10.0%) died. Median weaning time was shorter with tracheostomy collar use (15 days; IQR 8-25) than with pressure support (19 days; IQR 12-31), P = .004. The hazard ratio for successful weaning rate was higher with unassisted breathing than with pressure support (HR, 1.43; 95% CI, 1.03-1.98; P = 0.033) after adjusting for baseline clinical covariates. Mortality was equivalent in the pressure-support and unassisted breathing groups at 6 months (55.92% vs 51.25%; 4.67% difference, 95% CI −6.4% to 15.7%) and at 12 months (66.45% vs 60.00%; 6.45% difference, 95% CI −4.2% to 17.1%). Conclusion: In a long-term acute care hospital, weaning from prolonged mechanical ventilation was quicker with unassisted breathing through a tracheostomy than with pressure support; although there was no difference on medium term mortality.

Full Text: Jubran. Effect of Pressure Support vs Unassisted Breathing Through a Tracheostomy Collar on Weaning Duration in Patients Requiring Prolonged Mechanical Ventilation: A Randomized Trial. JAMA 2013;epublished January 22nd


New England Journal of Medicine:     High Frequency Oscillation

Ferguson and colleagues completed an international multicenter, randomized, controlled trial in adults with new-onset, moderate-to-severe ARDS comparing high flow oscillatory ventilation (HFOV, n=275) with conventional mechanical ventilation (n=273) using low tidal volumes and high positive end-expiratory pressure. The trial was terminated on the advice of the data monitoring committee after 548 of a planned 1200 patients had undergone randomization, due to excess mortality with HFOV (HFOV 47%, n=129 versus control: 35%, n=96; relative risk of death with HFOV, 1.33; 95% CI 1.09 to 1.64; P=0.005). Compared with the control group, patients in the HFOV group received higher doses of midazolam (199 mg per day [IQR 100 to 382] vs. 141 mg per day [IQR 68 to 240], P<0.001), as well as more patients receiving neuromuscular blockers (83% vs. 68%, P<0.001), and vasoactive drugs (91% vs. 84%, P=0.01) and received them for a longer period (5 days vs. 3 days, P=0.01) than did patients in the control group. Conclusion:  High frequency oscilatory ventilation was associated with increased mortality in comparison with conventional mechanical ventilation in adult patients with new-onset moderate-to-severe ARDS.

Full Text:  Ferguson. High-Frequency Oscillation in Early Acute Respiratory Distress Syndrome (OSCILLATE). New Engl J Med 2013;epublished January 22rd


Young et al performed a multicenter study, comparing HFOV (n=398) with conventional mechanical ventilation (n=397) in adults with moderate-to-severe ARDS. There was no  difference in mortality between modes of ventilation (HFOV 41.7%, n=166 versus CMV 41.1%, n=163; P=0.85). Similarly, there were no differences in the duration of antimicrobial agents (HFOV 12.8±12.0 days  vs CMV 12.4±10.3 days, P=0.56); duration of inotropic agents or pressor infusions (HFOV 2.9±4.5 days vs CMV 2.8±5.6 days; P=0.74); duration of ICU stay (HFOV 17.6±16.6 days vs CMV 16.1±15.2 days; P=0.18) or in durations of hospital stay ( HFOV 33.9±41.6 days vs 33.1±44.3 days; P=0.79). Conclusion: High frequency oscillatory ventilation was not superior to conventional mechanical ventilation for the management of moderate-to-severe ARDS.

Full Text:  Young. High-Frequency Oscillation for Acute Respiratory Distress Syndrome (OSCAR). New Engl J Med 2013;epublished January 22nd


Critical Care Medicine:     Surviving Sepsis Campaign Guidelines 2012


Critical Care Medicine:     Pain, Agitation & Delirium


Journal of the American Medical Association:     Gastric Feeding

To test the hypothesis that the risk of ventilator-associated pneumonia is not increased when residual gastric volume is not monitored compared with routine residual gastric volume monitoring Reignier and colleagues performed a randomized, noninferiority, open-label, multicenter trial in 9 French (ICUs) recruiting 452 adults requiring invasive mechanical ventilation for more than 2 days and given enteral nutrition within 36 hours after intubation. There was no difference in the incidence of VAP (interventional group: 38/227; 16.7%) versus control group (35/222 patients; 15.8%)  (difference: 0.9%; 90% CI: −4.8% to 6.7%). Similarly, there were no significant differences in other ICU-acquired infections, mechanical ventilation duration, ICU stay length, or mortality rates. The proportion of patients receiving 100% of their calorie goal was higher in the intervention group (odds ratio, 1.77; 90% CI, 1.25-2.51; P = .008). Conclusion: In critically ill mechanically ventilated patients receiving early nasogastric feeding, the absence of gastric volume monitoring was not inferior to routine residual gastric volume monitoring in terms of multiple outcomes, including the incidence of VAP.

Abstract:  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


Journal of the American Medical Association:     Out-of-Hospital Cardiac Arrest

To determine whether prehospital advanced airway management is associated with favorable outcome after adult out-of-hospital cardiac arrest, Hasegawa et al performed a prospective, nationwide, population-based study on the All-Japan Utstein Registry, involving 649 654 consecutive adult patients who had an OHCA and in whom resuscitation was attempted by emergency responders with subsequent transport to medical institutions. 367 837 (57%) underwent bag-valve-mask ventilation and 281 522 (43%) advanced airway management, including 41 972 (6%) with endotracheal intubation and 239 550 (37%) with use of supraglottic airways. Advanced airway management was associated with a lower rate of favorable neurological outcome compared with the bag-valve-mask group (1.1% vs 2.9%; OR: 0.38; 95% CI: 0.36-0.39). In a propensity score–matched cohort (357 228 patients), the adjusted odds of neurologically favorable survival were significantly lower both for endotracheal intubation (adjusted OR, 0.45; 95% CI, 0.37-0.55) and for use of supraglottic airways (adjusted OR, 0.36; 95% CI, 0.33-0.39). Conclusion: In a prospective registry study, in out-of-hospital cardiac arrest, in comparison with bag-valve-mask ventilation, both endotracheal intubation and supraglottic airway use were associated with decreased odds of neurologically favorable survival.

Abstract:  Hasegawa. Association of Prehospital Advanced Airway Management With Neurologic Outcome and Survival in Patients With Out-of-Hospital Cardiac Arrest. JAMA 2013;309(3):257


Critical Care:     Anti-Microbial Therapy

Díaz-Martín performed a national multicenter study  to investigate the impact of combination antimicrobial therapy within the first 6 hours of the diagnosis of severe sepsis or septic shock, including antimicrobials with different mechanisms of action (different-class combination therapy, DCCT), on mortality. 1,372 patients were enrolled, 1,022 (74.5%) with community-acquired sepsis and 350 (25.5%) with nosocomial sepsis. The most frequently prescribed antibiotic agents were β-lactams (902, 65.7%) and carbapenems (345, 25.1%). DCCT was administered to 388 patients (28.3%), and non-DCCT was administered to 984 (71.7%). DCCTs was associated with a lower mortality than non-DCCTs (34% vs 40%; P = 0.042). 

Full TextDíaz-Martín. Antibiotic prescription patterns in the empiric therapy of severe sepsis: combination of antimicrobials with different mechanisms of action reduces mortality Critical Care 2012;16:R223


Clinical Nutrition:     Effect of Feeding on Pneumonia

Jiyong and colleagues performed a systematic review and meta analysis comparing gastric with post-pyloric feeding on the incidence of pneumonia. 15 randomized clinical trials with 966 patients were included. Post-pyloric feeding was associated with reduction in pneumonia compared with gastric feeding (RR 0.63, 95% CI 0.48–0.83, p = 0.001; I2 = 0%). The risk of aspiration (RR: 1.11; 95% CI: 0.80–1.53, p = 0.55; I2 = 0%) and vomiting (RR, 0.80; 95% CI, 0.38–1.67, p = 0.56; I2 = 65.3%) were not significantly different between patients treated with gastric and post-pyloric feeding. Conclusion:  In critically ill patients, post-pyloric feeding, in comparison with gastric feeding, was associated with a reduced incidence of pneumonia

Full Text:  Jiyong. Effect of gastric versus post-pyloric feeding on the incidence of pneumonia in critically ill patients: Observations from traditional and Bayesian random-effects meta-analysis. Clinical Nutrition 2013;32(1):8-15


New England Journal of Medicine:     Clostridium Difficile Diarrhoea

Van Nood and colleagues completed an open-label, randomized, controlled trial in 42 patients with resistant C. difficile infection, comparing (1) an initial vancomycin regimen (500 mg orally four times per day for 4 days), followed by bowel lavage and subsequent infusion of a solution of donor faeces through a nasoduodenal tube (n=16); (2) a standard vancomycin regimen (500 mg orally four times per day for 14 days)(n=13); or (3) a standard vancomycin regimen with bowel lavage (n=13). The study was stopped after an interim analysis due a superior result with the first preparation, with 13 (81%) having resolution of C. difficile–associated diarrhoea after the first infusion. The 3 remaining patients received a second infusion with faeces from a different donor, with 2 patients being successfully treated. Resolution of C. difficile infection occurred in 4 of 13 patients (31%) receiving vancomycin alone and in 3 of 13 patients (23%) receiving vancomycin with bowel lavage (P<0.001 for both comparisons with the infusion group). No significant differences in adverse events among the three study groups were observed except for mild diarrhoea and abdominal cramping in the infusion group on the infusion day. Conclusion: Faecal transplantation following oral vancomycin therapy and bowel lavage was superior to either oral vancomycin and bowel lavage or oral vancomycin alone with respect to resolution of resistant C. difficile diarrhoea at 10 weeks post treatment.

Full Text:  Van Nood. Duodenal Infusion of Donor Feces for Recurrent Clostridium difficile. N Eng J Med 2013

Associated Editorial:  Kelly. Fecal Microbiota Transplantation — An Old Therapy Comes of Age. N Eng J Med 2013


Acta Anaesthesiologica Scandinavica:     Inotropic Support in Septic Shock

Wilkman et al performed a retrospective analysis of 420 subjects with septic shock, using both logistic regression and propensity scoring to analyse the association of inotrope treatment with 90-day mortality. One hundred eighty-six (44.3%) patients received inotrope treatment during the first 24 h in ICU. Of those, 168 (90.3%) received dobutamine, 29 (15.6%) levosimendan, and 23 (12.4%) epinephrine. Blood lactate (P < 0.001), central venous pressure, (P < 0.001), and norepinephrine dose (P  = 0.03) were independently associated with inotrope treatment. Patients with inotrope treatment had a higher 90-day mortality (42.5% vs. 23.9%, P < 0.001). Age (P < 0.001), APACHE II score (P < 0.001), and inotrope treatment (P = 0.003) were independently associated with 90-day mortality also after adjustment with propensity score. Conclusion: In this retrospective review, the use of inotrope treatment in septic shock was associated with increased 90-day mortality without and after adjustment with propensity to receive inotrope.

Abstract:  Wilkman. Association between inotrope treatment and 90-day mortality in patients with septic shock. Acta Anaesthesiologica Scandinavica 2013; epublished January 8th


New England Journal of Medicine:     Upper Gastrointestinal Haemorrhage

Villanueva et al performed a randomized study comparing the efficacy and safety of a restrictive transfusion strategy (Hb <7g/dL) with those of a liberal transfusion strategy (Hb<9g/dL) in 921 patients with severe acute upper gastrointestinal bleeding. More patients in the restrictive group did not receive a transfusion (n=225/51% versus n=65/15%, p<0.001). The restrictive practice was associated with numerous benefits, including increased probability of survival (95% versus 91%; hazard ratio for death 0.55; 95% CI: 0.33-0.92; p=0.02); decreased rebleeding (10% versus 16%, p=0.01) and adverse events (40% versus 48%, p=0.02). In subgroup analysis, restrictive transfusion was associated with improved probability of survival in patients with cirrhosis and Child–Pugh class A or B disease (HR 0.30; 95% CI 0.11 to 0.85), but not in those with cirrhosis and Child–Pugh class C disease (HR 1.04; 95% CI 0.45 to 2.37) or bleeding associated with a peptic ulcer (HR 0.70; 95% CI 0.26 to 1.25). Liberal transfusion was associated with an increase in portal-pressure gradient at 5 days (p=0.03). Conclusion: In a large multi-centre randomized study, red cell transfusion based on a haemoglobin threshold of 7g/dL in upper GI bleeding, was associated with improved mortality, reduced rebleeding rates and reduced adverse events than a transfusion policy based on a 9g/dL threshold.

Abstract:  Villanueva. Transfusion Strategies for Acute Upper Gastrointestinal Bleeding. N Engl J Med 2013;368:11-21



December 2012

Hepatology:     Extracorporeal Albumin Dialysis

Bañares and colleagues performed a prospective, randomized controlled trial in 189 patients with acute-on-chronic liver failure, comparing extracorporeal albumin dialysis (molecular adsorbent recirculating system (MARS), up to ten 6-8 hours sessions, n=95) or to standard therapy (n=94). A number of patients were excluded for protocol violations. Both groups were similar at baseline. There was no difference in  28-day survival, 60% vs 59%. After adjusting for confounders, MARS had no effect on survival (odds ratio: 0.87; CI 95 % 0.44-1.72). Severe adverse events were similar. Conclusion: In this study, MARS did not improve survival in acute-on-chronic liver failure, but did demonstrate a significant dialysis effect (lower creatinine, p=0.02 and lower bilirubin p=0.001). 

Abstract: Bañares. Extracorporeal albumin dialysis with the molecular adsorbent recirculating system in acute-on-chronic liver failure: The RELIEF trial. Hepatology 2012;epublished ahead of print


Annals of Internal Medicine:     Red Cell Transfusion

Chatterjee and colleagues performed a systematic review, meta analysis and diversity-adjusted study sequential analysis to investigate whether red cell transfusion is beneficial in the setting of myocardial infarction. Ten studies were included in the analysis. Comparing red cell transfusion with no transfusion during myocardial infarction, transfusion increased all-cause mortality (18.2% vs 10.2%) (risk ratio, 2.91; 95% CI, 2.46-3.44; P < 0.001), with a weighted absolute risk increase of 12% and a number needed to harm of 8 (95% CI, 6-17). Multivariate meta-regression revealed that blood transfusion was associated with a higher risk for mortality independent of baseline hemoglobin level, nadir hemoglobin level, and change in hemoglobin level during the hospital stay. Blood transfusion was also significantly associated with a higher risk for subsequent myocardial infarction (risk ratio, 2.04; 95% CI, 1.06-3.93; P = 0.03).

Abstract:  Chatterjee. Association of Blood Transfusion With Increased Mortality in Myocardial Infarction: A Meta-analysis and Diversity-Adjusted Study Sequential Analysis. Arch Intern Med 2012;epublished December 24th


Stroke:     Tracheostomy in Stroke

Bösel et al completed a single-centre, prospective, randomized, parallel-group, controlled, open, and outcome-masked pilot trial in 60 subjects with severe ischemic or hemorrhagic stroke and an estimated need for at least 2 weeks of ventilation. Subjects were randomized to either early tracheostomy (within day 1–3 from intubation; early) or to standard tracheostomy (between day 7–14 from intubation if extubation could not be achieved or was not feasible; standard). There were no differences were in length of ICU stay (median 18 [interquartile range 16–28] versus 17 [interquartile range 13–22] days, median difference: 1 [−2 to 6]; P=0.38) or to most secondary outcomes, including adverse effects. Use of sedatives (62% versus 42% of ICU stay, median difference 17.5 [3.3–29.2]; P=0.02), ICU mortality (ICU deaths 3 [10%] versus 14 [47%]; P<0.01) and 6-month mortality (deaths 8 [27%] versus 18 [60%]; P=0.02) were lower in the early group than in the standard group, respectively.

Abstract: Bösel. Stroke-Related Early Tracheostomy Versus Prolonged Orotracheal Intubation in Neurocritical Care Trial (SETPOINT): A Randomized Pilot Trial. Stroke 2012;44:21-28


The Lancet:     Neuroprostheses

Collinger et al report prosthetic upper limb function in a previously tetraplegic patient with two 96-channel intracortical microelectrodes in the motor cortex followed by brain—machine-interface training for 13 weeks.  The participant was able to use the prosthetic limb to do skilful and coordinated reach and grasp movements that resulted in clinically significant gains in tests of upper limb function. No adverse events were reported.


Amercan Journal of Respiratory and Critical Care Medicine:     Fluid Management

Dessap et al performed a randomized controlled multicenter study, in 304 critically ill patients mechanically ventilated with an automatic computer-driven weaning system, to investigate whether fluid management guided by daily BNP plasma levels improved weaning compared with empirical therapy dictated by clinical acumen. In the BNP-driven group, furosemide and acetazolamide were given more often and in higher doses than in the control group, resulting in a more negative median (interquartile range) fluid balance during weaning (–2,320 [–4,735, 738] vs. -180 [–2,556, 2,832] ml; P < 0.0001). Time to successful extubation was significantly shorter with the BNP-driven strategy (58.6 [23.3, 139.8] vs. 42.4 [20.8, 107.5] h; P = 0.034). The BNP-driven strategy increased the number of ventilator-free days but did not change length of stay or mortality. The effect on weaning time was strongest in patients with left ventricular systolic dysfunction. The two strategies did not differ significantly regarding electrolyte imbalance, renal failure, or shock.

Abstract:  Dessap. Natriuretic Peptide–driven Fluid Management during Ventilator Weaning: A Randomized Controlled Trial. Am J Respir Crit Care Med 2012;186:1256-1263


Lancet:     Parenteral Nutrition

Heidegger et al performed a two-centre randomized controlled trial comparing enteral nutrition with additional supplemental parenteral nutrition (n=153), to achieve 100% energy target, with just enteral nutrition alone (n=152), in patients on day 3 of their ICU admission who had received less than 60% of their energy target from enteral nutrition. 30 patients did not complete the study. Mean energy delivery between day 4 and 8, the supplemented group received a mean daily energy intake of 28 kcal/kg (SD 5) (103% [SD 18%] of energy target), compared with 20 kcal/kg per day (7) for the non-supplemented group group (77% [27%]). The rate of nosocomial infection between days 9 and 28 was 27% for the supplememntal group and 38% for the non-supplemented group (hazard ratio 0·65, 95% CI 0·43—0·97; p=0·0338). The supplemental group had a lower mean number of nosocomial infections per patient (−0·42 [−0·79 to −0·05]; p=0·0248).

Abstract:  Heidegger. Optimisation of energy provision with supplemental parenteral nutrition in critically ill patients: a randomised controlled clinical trial. Lancet 2012; epublished ahead of print


Clinical Infectious Disease:     Hydrogen Peroxide Vapour Cleansing

In a single centre 30-month prospective cohort intervention study, comparing hydrogen peroxide vaporization with standard disinfection, on acquisition rates of multi-drug resistant infection after admission to a room previously inhabited by a patient with an MDR microbe. There were 1397 episodes of admission into a room previously inhabited by a patient with a MDR microbe. Patients admitted to a HPV treated room were 64% less likely to acquire a MDR microbe (incidence rate ratio 0.36; 95% CI 0.19–0.70; P < 0.001) and 80% less likely to acquire vancomycin resistant enterococci (IRR, 0.20; 95% CI, 0.08–0.52; P < 0.001) after adjusting for other factors. The risk of reducing individual infection was not reduced for MRSA, C.diff, and gram negative rods. The proportion of rooms environmentally contaminated with MDR organisms was reduced significantly after HPV cleansing (relative risk, 0.65, P = .03), but not with standard cleansing.

Abstract:  Passaretti. An Evaluation of Environmental Decontamination With Hydrogen Peroxide Vapor for Reducing the Risk of Patient Acquisition of Multidrug-Resistant Organisms. Clin Infect Disease 2013;56(1):27-35


New England Journal of Medicine:     Traumatic Brain Injury

Chesnut and colleagues performed a randomized controlled trial in 324 patients in Bolivia and Equador with severe traumatic brain injury comparing intracranial pressure guided management with management based on a combination of imaging and clinical findings. There was no difference between groups in the primary outcome, a composite value of 21 functional and cognitive measures (p=0.49). Similarly, there was no difference in 6 month mortality (pressure guided 39% versus imaging-clinical guided 41%, p=0.60), median ICU length of stay (pressure guided 12 days versus imaging-clinical guided 9 days, p=0.25). There were more days of administration of specific brain therapies in the imaging-clinical group (4.8 versus 3.4, p=0.002). 

Full Text: Chesnut. A Trial of Intracranial-Pressure Monitoring in Traumatic Brain Injury. New Engl J Med 2012; epublished December 12th

Critical Care:     Statins in Sepsis

Patel and colleagues completed a single centre phase II randomized double-blind placebo-controlled trial, comparing atorvastatin 40mg daily (n=49) or placebo (n=51), on the rate of sepsis progressing to severe sepsis during hospitalization in 100 statin-naïve subjects. Statin therapy appeared to have a therapeutic effect, with less statin treated patients progressing to severe sepsis (4% versus 24%, p=0.007; NNT=7). However, the clinical effects of this were less apparent, with no difference noted in length of hospital stay, critical care unit admissions, 28-day and 12-month readmissions or mortality, although the numbers recruited may have been too low to adequately address this. Statin therapy was associated with reductions in both plasma cholesterol, as expected, and the urinary albumin creatinine ratio, a marker of endothelial dysfunction.  Adverse events were similar in the two groups.

Full Text:  Patel. Randomized double-blind placebo-controlled trial of 40 mg/day of atorvastatin in reducing the severity of sepsis in ward patients (ASEPSIS Trial). Critical Care 2012;16:R231


UK Intensive Care Society State of the Art Meeting - Clinical Trials Update Session

These results are provisional, and may contain inaccuracies, as I tried to keep track of the data as it was presented.



Dr Anthony Gordon presented early results from the VACS (Vasopressin and Corticosteroids in septic Shock) trial. This open-label randomised controlled trial was a feasibility study for a larger double-blind randomised controlled trial comparing vasopressin with noradrenaline (VANISH) and recruited 63 adult patients requiring vasopressors for the management of septic shock. The study compared vasopressin (0 - 0.06 U/minute infusion) and hydrocortisone sodium phosphate (50 mg IV 6-hourly) (n=31) with vasopressin (0 - 0.06 U/minute infusion) and placebo (0.5 ml 0.9% saline IV 6 hourly) (n=33). Vasopressin plus steroid therapy had a sparing effect on total vasopressin dose administered and was associated with a three day earlier resolution of shock. 28 day mortality was identical between the two groups (25%), as were organ failure scores.

BALTI Prevention

Prof Gavin Perkins presented the initial results of the randomized placebo controlled BALTI Prevention study, investigating the efficacy of inhaled salbutamol for the prevention of acute lung injury after transthoracic oesophagectomy. 179 subjects received salbutamol and 183 received placebo. 79% of subjects were male with a mean age of 63 years. Subjects received one lung ventilation intraoperatively, with a mean duration of 143 minutes. There was no difference between groups in either the incidence of ALI (approximately 20% each) or degree of extravascular lung water. Similarly there were no differences in oxygenation, duration of ventilation or organ support.


Dr Valerie Page presented very preliminary findings (only received the night before) from the HOPE-ICU study, a phase II single-centre randomised, double-blind, placebo controlled trial comparing the early administration of intravenous haloperidol versus placebo in the prevention and treatment of delirium in critically ill ventilated patients. The intervention was 2.5 mg haloperidol intravenously or 0.5 ml normal saline intravenously 8 hourly for up to 14 days or until the patient screened negative for delirium for 48 hours using the CAM-ICU. 52, primarily male subjects, with a mean age of 68 years were recruited to both arms. The incidence of sepsis was approximately 50% in both groups. There was no difference in the primary outcome of the number of delirium/coma free days, measured at 14 days. 


Dr Duncan Young presented the preliminary findings of the OSCAR study, a prospective, randomized controlled pragmatic effectiveness study in subjects with severe ARDS, comparing high frequency oscillation (HVO) with standard conventional mechanical ventilation (CMV). 795 subjects (60% with a PaO2/Fi02 ratio of < 15) were recruited within 7 days of the initiation of mechanical ventilation. HVO dose was determined by 2 algorithms for the management of both oxygen and carbon dioxide. There was no difference in the primary endpoint of 30 day mortality between the 2 arms (HVO 58.3% versus CMV 58.8; p=0.85). Similarly, the length of hospital stay was 21 days in each arm. Other presented secondary outcomes were also not different. Analysis is ongoing with publication expected early in the 2013.

Dr Young compared his findings with that of the Canadian OSCILLATE study, a prospective randomized controlled efficacy study also comparing HVO with CMV, which he reported as being terminated after recruiting less than 600 of a planned 1200 patients, after an interim analysis showed an 11% absolute excess mortality with HFO therapy (approx 30 day mortality 41% versus 29%). Analysis of trial data is ongoing. I’m not aware of these findings having been previously released.

An individual patient data meta analysis combining these two studies is planned.


November 2012

Journal of the American Medical Association:     Traumatic Brain Injury

To determine whether citicoline can improve functional and cognitive status in people with traumatic brain injury (TBI), Zafonte et al performed a phase 3, double-blind randomized, placebo controlled trial in 1213 patients. Subjcets received either 90 days of 2g oral or enteral citicoline daily or placebo and were assessed at 90 days using the TBI-Clinical Trials Network Core Battery. There was no difference in rates of favorable improvement for the Glasgow Outcome Scale–Extended; citicoline: 35.4% versus placebo: 35.6%. The citicoline and placebo groups did not differ significantly at 90 days (global odds ratio [OR], 0.98 [95% CI, 0.83-1.15]); in addition, there was no significant treatment effect in the 2 severity subgroups (global OR, 1.14 [95% CI, 0.88-1.49] and 0.89 [95% CI, 0.72-1.49] for moderate/severe and complicated mild TBI, respectively). At the 180-day evaluation, the citicoline and placebo groups did not differ significantly with respect to the primary outcome (global OR, 0.87 [95% CI, 0.72-1.04]).

Abstract:  Zafonte. Effect of Citicoline on Functional and Cognitive Status Among Patients With Traumatic Brain Injury: Citicoline Brain Injury Treatment Trial (COBRIT). JAMA 2012;308(19):1993


Journal of the American Medical Association:     Atrial Fibrillation

To determine whether perioperative long-chain n-3-polyunsaturated fatty acids (n-3-PUFA) supplementation reduces atrial fibrillation after cardiac surgery, Mozaffarian et al completed an international multi-centre, double-blind, placebo-controlled, randomized clinical trial in 1516 patients.  Patients were randomized to receive fish oil (1-g capsules containing ≥840 mg n-3-PUFAs as ethyl esters) or placebo, with preoperative loading of 10 g over 3 to 5 days (or 8 g over 2 days) followed postoperatively by 2 g/d until hospital discharge or postoperative day 10, whichever came first.The mean patient age was 64 (SD, 13) years; 72.2% of patients were men, and 51.8% had planned valvular surgery. There was no difference in the occurance of atrial fibrillation: placebo 233 (30.7%) versus n-3-PUFAs 227 (30.0%); (odds ratio, 0.96 [95% CI, 0.77-1.20]; P = 0.74). None of the secondary end points were significantly different between the placebo and fish oil groups, including postoperative AF that was sustained, symptomatic, or treated (231 [30.5%] vs 224 [29.6%], P = .70) or number of postoperative AF episodes per patient (1 episode: 156 [20.6%] vs 157 [20.7%]; 2 episodes: 59 [7.8%] vs 49 [6.5%]; ≥3 episodes: 18 [2.4%] vs 21 [2.8%]) (P = 0.73). Supplementation with n-3-PUFAs was generally well tolerated, with no evidence for increased risk of bleeding or serious adverse events.

Abstract: Mozaffarian. Fish Oil and Postoperative Atrial Fibrillation: The Omega-3 Fatty Acids for Prevention of Post-operative Atrial Fibrillation (OPERA) Randomized Trial. JAMA 2012;308(19):2001


Archives of Surgery:     Traumatic Brain Injury

To investigate the relationship between oxygenation and short-term outcomes in patients with traumatic brain injury, Brenner and colleagues performed a retrospective review of 1547 consecutive patients with TBI who survived at least 12 hours after hospital admission. The majority of patients were male (77%) and had received blunt trauma (89%). Mean (SD) age, admission GCS score, and Injury Severity Score were 41.3 (20.6) years, 8.3 (4.7), and 31.9 (12.5), respectively. Mean (SD) intensive care unit length of stay and hospital length of stay were 8.7 (10.5) days and 13.8 (13.7) days, respectively. Mean (SD) discharge GCS score was 10.1 (4.7). The mortality rate was 28%. After controlling for several factors patients with hyperoxaemia had lower GCS at discharge, and those with either hyperoxaemia or hypoxaemia had higher mortality, than noroxaemic patients (all P< 0.05).

Abstract: Brenner. Association Between Early Hyperoxia and Worse Outcomes After Traumatic Brain Injury. Arch Surg 2012;147(11):1042 


Archives of Surgery:     Fibrinogen in Trauma

To evaluate the effect of fibrinogen-containing cryoprecipitate in addition to the antifibrinolytic tranexamic acid on survival in combat injuries, Morrison et al undertook a retrospective observational study in 1332 patients, whose data had been prospectively recorded by UK and US trauma registeries during treatment at a Role 3 Combat Surgical Hospital in Southern Afghanistan. All patients had required at least 1 unit of packed red blood cells and composed the following groups: tranexamic acid (n = 148), cryoprecipitate (n = 168), tranexamic acid/cryoprecipitate (n = 258), and no tranexamic acid/cryoprecipitate (n = 758). Injury Severity Scores were highest in the cryoprecipitate (n=168; mean [SD], 28.3 [15.7]) and tranexamic acid/cryoprecipitate (n=258; 26 [14.9]) groups compared with the tranexamic acid (n=148; 23.0 [19.2]) and no tranexamic acid/cryoprecipitate (n=758; 21.2 [18.5]) (P < .001) groups. Despite greater Injury Severity Scores and packed red blood cell requirements, mortality was lowest in the tranexamic acid/cryoprecipitate (11.6%) and tranexamic acid (18.2%) groups compared with the cryoprecipitate (21.4%) and no tranexamic acid/cryoprecipitate (23.6%) groups. Tranexamic acid and cryoprecipitate were independently associated with a similarly reduced mortality (odds ratio, 0.61; 95% CI, 0.42-0.89; P = 0.01 and odds ratio, 0.61; 95% CI, 0.40-0.94; P = 0.02, respectively). The combined tranexamic acid and cryoprecipitate effect vs neither in a synergy model had an odds ratio of 0.34 (95% CI, 0.20-0.58; P < 0.001), reflecting nonsignificant interaction (P = 0.21).

AbstractMorrison. Association of Cryoprecipitate and Tranexamic Acid With Improved Survival Following Wartime InjuryFindings From the MATTERs II Study. Arch Surg 2012; epublished November 19th


Lancet:     Acute Heart Failure

Teerlink et al performed an international, double-blind, placebo-controlled trial, investigating Serelaxin (recombinant human relaxin-2) in 1161 patients admitted to hospital for acute heart failure. Serelaxin (n=581) improved one primary outcome of change from baseline dyspnoea score, as measured with a visual analog scale (448 mm × h, 95% CI 120—775; p=0·007), but not the other primary outcome of effect on the proportion of patients with moderate or marked dyspnoea improvement measured by Likert scale during the first 24 hours (Likert scale; placebo: 150 patients [26%]; serelaxin: 156 [27%]; p=0·70). No significant effects were recorded for the secondary endpoints of cardiovascular death or readmission to hospital for heart failure or renal failure (placebo: 75 events [60-day Kaplan-Meier estimate, 13·0%]; serelaxin: 76 events [13·2%]; hazard ratio [HR] 1·02 [0·74—1·41], p=0·89] or days alive out of the hospital up to day 60 (placebo: 47·7 [SD 12·1] days; serelaxin: 48·3 [11·6]; p=0·37). Serelaxin treatment was associated with significant reductions of other prespecified additional endpoints, including fewer deaths at day 180 (placebo: 65 deaths; serelaxin: 42; HR 0·63, 95% CI 0·42—0·93; p=0·019).

Abstract:  Teerlink. Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure (RELAX-AHF): a randomised, placebo-controlled trial. Lancet 2012; epublished November 7th


Annals of Internal Medicine:     C. Diff Diarrhoea

Johnstone et al undertook a systematic review and meta analysis, including 20 trials (n=3818), to assess the efficacy and safety of probiotics for the prevention of Clostridium difficileassociated diarrhea (CDAD) in adults and children receiving antibiotics. Probiotics reduced the incidence of CDAD by 66% (pooled relative risk, 0.34 [95% CI, 0.24 to 0.49]; I2 = 0%). In a population with a 5% incidence of antibiotic-associated CDAD (median control group risk), probiotic prophylaxis would prevent 33 episodes (CI, 25 to 38 episodes) per 1000 persons. Of probiotic-treated patients, 9.3% experienced adverse events, compared with 12.6% of control patients (relative risk 0.82 [CI, 0.65 to 1.05]; I2 = 17%). In 13 trials, data on CDAD were missing for 5% to 45% of patients, although results were robust to worst-plausible assumptions regarding event rates in studies with missing outcome data.

Abstract:  Johnston. Probiotics for the Prevention of Clostridium difficile–Associated Diarrhea: A Systematic Review and Meta-analysis. Ann Intern Med 2012; epublished November 13th


Intensive Care Medicine:    Hospital-Acquired Bloodstream Infections

Tabah et al undertook a prospective, multicentre non-representative cohort study in 162 ICUs in 24 countries to investigate the epidemiology of hospital-acquired bloodstream infections (HA-BSIs) and evaluated the impact of drug resistance on outcomes of critically ill patients.  1,156 patients with with HA-BSIs were enrolled, with 76 % of infections being ICU-acquired. The median time to diagnosis was 14 [IQR: 7–26] days after hospital admission. 12% of infections were polymicrobial. Of monomicrobial infections, 58.3 % were gram-negative, 32.8 % gram-positive, 7.8 % fungal and 1.2 % due to strict anaerobes. Overall, 629 (47.8 %) isolates were multidrug-resistant (MDR), including 270 (20.5 %) extensively resistant (XDR), and 5 (0.4 %) pan-drug-resistant (PDR). Micro-organism distribution and MDR occurrence varied significantly (p < 0.001) by country. The 28-day all-cause fatality rate was 36 %. In a multivariable model, independent predictors of 28-day mortality included MDR isolate [OR: 1.49; 95 % CI: 1.07–2.06], uncontrolled infection source (OR: 5.86; 95 % CI: 2.5–13.9) and timing to adequate treatment (before day 6 since blood culture collection versus never, OR 0.38; 95 % CI: 0.23–0.63; since day 6 versus never, OR 0.20; 95 % CI: 0.08–0.47).

Abstract:  Tabah. Characteristics and determinants of outcome of hospital-acquired bloodstream infections in intensive care units: the EUROBACT International Cohort Study. Intensive Care Medicine 2012;38,12:1930-1945


New England Journal of Medicine:     Cardiac Arrest

To determine whether survival and neurologic function after in-hospital cardiac arrest have improved over time, Girota et al interogated the Get with Guidelines–Resuscitation Registry from 2000 and 2009. In 374 hospitals, 84,625 hospitalized patients had a cardiac arrest, with 79.3% had an initial rhythm of asystole or pulseless electrical activity, and 20.7% had ventricular fibrillation or pulseless ventricular tachycardia. The proportion of cardiac arrests due to asystole or pulseless electrical activity increased over time (P<0.001 for trend). Risk-adjusted rates of survival to discharge increased from 13.7% in 2000 to 22.3% in 2009 (adjusted rate ratio per year, 1.04; 95% CI, 1.03 to 1.06; P<0.001 for trend). Survival improvement was similar in the two rhythm groups and was due to improvement in both acute resuscitation survival and postresuscitation survival. Rates of clinically significant neurologic disability among survivors decreased over time, with a risk-adjusted rate of 32.9% in 2000 and 28.1% in 2009 (adjusted rate ratio per year, 0.98; 95% CI, 0.97 to 1.00; P=0.02 for trend).

Abstract:  Girotra. Trends in Survival after In-Hospital Cardiac Arrest. N Engl J Med 2012;367:1912-192


New England Journal of Medicine:     Acute Heart Failure

Bart and colleagues undertook a prospective randomized trial in 188 patients with acute decompensated heart failure, worsened renal function, and persistent congestion, comparing stepped pharmacologic therapy (n=94) with ultrafiltration (n=94). The pharmacological strategy aimed to produce a urinary output of 3 - 5 l of urine per day (described in full here), while the UF removed fluid at 200 ml/hr. At 96 hours ultrafiltration was inferior to pharmacologic therapy with respect to the primary end point of change in serum creatinine level and body weight (P=0.003). Creatinine increased in the UF group, but not in the pharmacological group (UF: creatinine +20.3±61.9 μmol/l v pharmaological therapy: −3.5±46.9 μmol/l; P=0.003). There was no significant difference in weight loss at 96 hours (UF: - 5.7±3.9 kg v pharmacological therapy: -5.5±5.1 kg; P=0.58). There were more serious adverse events in the UF group (72% vs. 57%, P=0.03).

Full Text:  Bart. Ultrafiltration in Decompensated Heart Failure with Cardiorenal Syndrome (CARRESS). N Engl J Med 2012; epublished November 6th

Associated Editorial:  Tang. Reconsidering Ultrafiltration in the Acute Cardiorenal Syndrome. N Engl J Med 2012; epublished November 6th


New England Journal of Medicine:     Pay-for-Performance

Sutton et al investigated the efficacy of pay-for-performance on 30-day in-hospital mortality in 134,435 patients admitted for pneumonia, heart failure, or acute myocardial infarction to 24 hospitals in the North-East of England (population 6.8 million). Difference-in-differences regression analysis was used to compare mortality 18 months before and 18 months after the introduction of the program with mortality in two comparators: 722,139 patients admitted for the same three conditions to the 132 other hospitals in England and 241,009 patients admitted for six other conditions to both groups of hospitals. Risk-adjusted, absolute mortality decreased significantly with pay-fpr-performance, with an absolute reduction of 1.3 percentage points (95% CI: 0.4 to 2.1; P=0.006) and a relative reduction of 6%, equivalent to 890 fewer deaths (95% CI: 260 to 1500) during the 18-month period. The largest reduction was for pneumonia, (1.9 percentage points; 95% CI: 0.9 to 3.0; P<0.001), with nonsignificant reductions for acute myocardial infarction (0.6 percentage points; 95% CI:, −0.4 to 1.7; P=0.23) and heart failure (0.6 percentage points; 95% CI: −0.6 to 1.8; P=0.30).

Full Text:  Sutton. Reduced Mortality with Hospital Pay for Performance in England. N Engl J Med 2012;367:1821-1828

Circulation:     Therapeutic Hypothermia

In a prospective randomized pilot trial Lopez-de-Sa and colleagues compared 32°C (n=18) with 34°C (n=18) for therapeutic hypothermia post witnessed out-of-hospital cardiac arrest. Twenty six subjects had a shockable rhythm and 10 were asystolic. The primary outcome of survival free from severe dependence (Barthel Index score ≥60 points) at 6 months occurred more often in the 32°C group (8/18,44.4%) than in the 34°C group (2/18;11.1%) (log-rank P=0.12). All patients whose initial rhythm was asystole died before 6 months in both groups. Eight of 13 patients (61.5%) with initial shockable rhythm assigned to 32°C were alive free from severe dependence at 6 months compared with 2 of 13 (15.4%) assigned to 34°C (log-rank P=0.029). The incidence of complications was similar in both groups except for the incidence of clinical seizures, which was lower (1 versus 11; P=0.0002) in patients assigned to 32°C compared with 34°C. There was a trend toward a higher incidence of bradycardia (7 versus 2; P=0.054) in patients assigned to 32°C. Although potassium levels decreased to a greater extent in patients assigned to 32°C, the incidence of hypokalemia was similar in both groups.

Full Text: Lopez-de-Sa. Hypothermia in Comatose Survivors From Out-of-Hospital Cardiac Arrest: Pilot Trial Comparing 2 Levels of Target Temperature. Circulation 2012; epublished November 6th


Journal of the American Medical Association:     Dexamethasone in Cardiac Surgery

Dieleman et al performed a multicenter, randomized, double-blind, controlled trial compared 1mg/kg of intraoperative dexamethasone (n=2239) with placebo (n=2255) on the incidence of major adverse events in patients undergoing cardiac surgery. There was no difference in the primary composite outcome of death, myocardial infarction, stroke, renal failure, or respiratory failure, within 30 days of randomization (dex: 157/2239;7.0% versus 191/2255;8.5%); relative risk: 0.83; 95% CI, 0.67-1.01; absolute risk reduction: −1.5%; 95% CI: −3.0% to 0.1%; P=0.07). Dexamethasone was associated with reductions in postoperative infection, duration of postoperative mechanical ventilation, and lengths of intensive care unit and hospital stays. In contrast, dexamethasone was associated with higher postoperative glucose levels.

Abstract: Dieleman. Intraoperative High-Dose Dexamethasone for Cardiac Surgery - A Randomized Controlled Trial (Dexamethasone for Cardiac Surgery (DECS) Study). JAMA 2012;308(17):1761-1767


Journal of the American Medical Association:     Myocardial Infarction

Traverse et al performed a randomized, 2 × 2 factorial, double-blind, placebo-controlled trial comparing intracoronary infusion of  bone marrow cells (BMCs) or placebo in 120 patients with left ventricular dysfunction  after successful primary percutaneous coronary intervention of anterior STEMI.  Therapy was administered  either 3 or 7 days (randomized 1:1) post PCI and within 12 hours of aspiration and cell processing. The mean (SD) patient age was 56.9 (10.9) years and 87.5% of participants were male. At 6 months, there was no significant increase in LV ejection fraction with BMCs (45.2% to 48.3%) vs the placebo  (44.5% to 47.8%; P = 0.96), or regional left ventricular function in either infarct or border zones. There was no change in global LV function for patients treated at day 3 (−0.9%; 95% CI: −6.6% to 4.9%; P = 0.76) or day 7 (1.1%; 95% CI: −4.7% to 6.9%; P = 0.70). Major adverse events were rare among all treatment groups.

Full Text:  Traverse. Effect of the Use and Timing of Bone Marrow Mononuclear Cell Delivery on Left Ventricular Function After Acute Myocardial Infarction: The TIME Randomized Trial. JAMA 2012; epublished November 2012


New England Journal of Medicine:     Coronary Revascularization

Farkouh and collegues completed a multi-centre, international randomized trial, comparing PCI with drug-eluting stents or CABG in 1900 diabetic patients with multivessel coronary artery disease. The patients' mean age was 63.1±9.1 years, 29% were women, and 83% had three-vessel disease. At 5 years, the primary outcome, a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke, was decreased with CABG (18.7% v 26.6%, p=0.005). The benefit of CABG was driven by differences in rates of both myocardial infarction (P<0.001) and death from any cause (P=0.049). Stroke was more frequent in the CABG group, with 5-year rates of 5.2% vs 2.4%; P=0.03.

Full Text:  Farkouh. Strategies for Multivessel Revascularization in Patients with Diabetes (FREEDOM Trial). N Engl J Med 2012, epublished November 4th

Associated Editorial: Hlatky. Compelling Evidence for Coronary-Bypass Surgery in Patients with Diabetes. N Engl J Med 2012, epublished November 4th


Nephrology Dialysis Transplantation:     AKI Biomarkers

Vanmassenhove et al performed a review of all papers investigating the utility of acute kidney injury biomarkers in 5 clinical settings - paediatrics, cardiac surgery, emergency medicine, critically care and contrast-induced nephropathy. The biomarkers investigated were neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, Cystatin C, interleukin-6, interleukin-8, interleukin-18, N-acetyl-glucosaminidase, glutathione transferases and liver fatty acid binding protein. Of 87 relevant papers  identified (74 studies), up to 27 different definitions of AKI were used. Reported diagnostic performance of the different biomarkers was variable from poor to excellent. As no consistent generalizable conclusions could be drawn on their diagnostic value, further research is required before they gain a place in routine clinical practice .

Abstract: Vanmassenhove. Urinary and serum biomarkers for the diagnosis of acute kidney injury: an in-depth review of the literature. Nephrol Dial Transplant 2012 epublished ahead of print Oct 31


October 2012

New England Journal of Medicine:     Fluids

Myburgh et al performed a large (n=7000), multi-centre, randomized controlled, blinded trial to assess the safety and efficacy of hydroxyethyl starch  {6% HES 130/0.4 (Voluven)} versus saline for fluid resuscitation in the ICU.  There was no overall mortality difference {HES: 597/3315 (18.0%) vs Saline: 566/3336 (17.0%); Relative risk: HES group, 1.06; 95% CI: 0.96 to 1.18; P=0.26) or mortality difference in the six predefined subgroups. Renal replacement therapy was used more often in the HES group {235/3352 patients (7.0%) vs 196/3375 (5.8%); RR: 1.21; 95% CI: 1.00 to 1.45; P=0.04}. Renal injury occurred more commonly in the HES group (34.6% vs 38.0%; P=0.005), although renal failure occurred equally in both groups (HES: 10.4% vs Saline: 9.2%; P=0.12). HES was associated with significantly more adverse events (5.3% vs. 2.8%, P<0.001).

Full Text:  Myburgh. Hydroxyethyl Starch or Saline for Fluid Resuscitation in Intensive Care (CHEST study). NEJM 2012; epublished ahead of print


Journal of the American Medical Association:     Sedation

In a randomized controlled trial, Mehta and colleagues compared protocolized sedation (n = 209) with protocolized sedation plus daily sedation interruption (n = 214) in mechanically ventilated critically ill patients. Median time to successful extubation was 7 days in both the interruption and control groups (median [IQR], 7 [4-13] vs 7 [3-12]; interruption group hazard ratio, 1.08; 95% CI, 0.86-1.35; P = 0.52). Duration of ICU stay (median [IQR], 10 [5-17] vs 10 [6-20]; P = 0.36) and hospital stay (median [IQR], 20 [10-36] vs 20 [10-48]; P = 0.42) did not differ between the daily interruption and control groups, respectively. Daily interruption was associated with higher mean daily doses of midazolam (102 mg/d vs 82 mg/d; P = 0.04) and fentanyl (median [IQR], 550 [50-1850] vs 260 [0-1400]; P < 0.001) and more daily boluses of benzodiazepines (mean, 0.253 vs 0.177; P = 0.007) and opiates (mean, 2.18 vs 1.79; P < 0.001). Unintentional endotracheal tube removal occurred in 10 of 214 (4.7%) vs 12 of 207 patients (5.8%) in the interruption and control groups, respectively (relative risk, 0.82; 95% CI, 0.36-1.84; P = 0.64). Rates of delirium were not significantly different between groups (53.3% vs 54.1%; relative risk, 0.98; 95% CI, 0.82-1.17; P = 0.83). Nurse workload was greater in the interruption group (VAS score, 4.22 vs 3.80; mean difference, 0.41; 95% CI, 0.17-0.66; P = 0.001).

Full Text:  Mehta. Daily Sedation Interruption in Mechanically Ventilated Critically Ill Patients Cared for With a Sedation Protocol. A Randomized Controlled Trial (SLEAP study). JAMA 2012; epublished ahead of print


Journal of the American Medical Association:     Red Cell Transfusion   (neonatal study)

Fergusson et al performed a double-blind, randomized controlled trial to determine if red blood cells stored for 7 days or less (n=188), compared with red cells issued in a standard manner (n=189), decreased rates of major nosocomial infection and organ dysfunction in neonatal intensive care unit patients requiring at least 1 RBC transfusion. The mean age of transfused blood was 5.1 (SD, 2.0) days in the fresh RBC group and 14.6 (SD, 8.3) days in the standard group. Of those in the fresh RBC group, 99 (52.7%) had the primary outcome (a composite measure of major neonatal morbidities, including necrotizing enterocolitis, retinopathy of prematurity, bronchopulmonary dysplasia, and intraventricular hemorrhage, and death) compared with 100 (52.9%) in the standard RBC group (relative risk, 1.00; 95% CI, 0.82-1.21). The rate of clinically suspected infection in the fresh RBC group was 77.7% (n = 146) compared with 77.2% (n = 146) in the standard RBC group (relative risk, 1.01; 95% CI, 0.90-1.12), and the rate of positive cultures was 67.5% (n = 127) in the fresh RBC group compared with 64.0% (n = 121) in the standard RBC group (relative risk, 1.06; 95% CI, 0.91-1.22).

Full Text:  Fergusson. Effect of Fresh Red Blood Cell Transfusions on Clinical Outcomes in Premature, Very Low-Birth-Weight Infants: The ARIPI Randomized Trial. JAMA 2012;308(14):1


New England Journal of Medicine:     Acute Coronary Syndrome

In 7243 patients with acute coronary syndrome not treated with revascularization, Roe et al compared prasugrel (10 mg daily) with clopidogrel (75 mg daily) in a double-blind, randomized trial. At 17 months there was no difference in the primary end point of death from cardiovascular causes, myocardial infarction, or stroke (prasugrel: 13.9% vs clopidogrel: 16.0%; prasugrel hazard ratio 0.91; 95% CI: 0.79 to 1.05; P=0.21).  A prespecified analysis of multiple recurrent ischemic events (all components of the primary end point) suggested a lower risk for prasugrel among patients under the age of 75 years (hazard ratio, 0.85; 95% CI, 0.72 to 1.00; P=0.04). Rates of intracranial bleeding and nonhemorrhagic serious adverse events were similar in the two groups, although there was a higher frequency of heart failure in the clopidogrel group. 

Abstract:  Roe. Prasugrel versus Clopidogrel for Acute Coronary Syndromes without Revascularization (The TRILOGY ACS Study). N Engl J Med 2012; 367:1297-1309

American Journal of Respiratory and Critical Care Medicine:     Catheter-Related Infections

Timsit et al performed an assessor-blinded randomized trial in 1879 patients with vascular catheters (4163 catheters, 34,339 catheter-days) comparing chlorhexidine dressings, highly adhesive dressings, and standard dressings on rates of catheter-related infections and catheter detachment.   The chlorhexidine dressings were associated with a 67% lower rate of major catheter-related infections (0.7/1000 vs. 2.1/1000 catheter-days; hazard ratio [HR], 0.328; 95% CI: 0.174-0.619 P=0.0006) and a 60% lower rate of catheter-related blood stream infections  (0.5/1000 vs. 1.3/1000 catheter-days; HR, 0.402; 95% CI, 0.186-0.868, P=0.02) than with non-chlorhexidine dressings. Decreases were noted in catheter colonization and skin colonization rates at catheter removal. The contact dermatitis rate was 1.1% with and 0.29% without chlorhexidine. Highly adhesive dressings decreased the detachment rate to 64.3% vs. 71.9% (P<0.0001) and the number of dressings per catheter to 2 (1-4) vs. 3 (1-5) (P<0.0001) but increased skin colonization (P<0.0001) and catheter colonization (HR=1.650; 95%CI, 1.21-2.26; P=0.0016) without influencing CRI or CR-BSI rates.

Abstract:  Timsit. Randomized Controlled Trial of Chlorhexidine Dressing and Highly Adhesive Dressing for Preventing Catheter-Related Infections in Critically Ill Adults. Am J Respir Crit Care Med epublished 4 October 2012

Critical Care:     Non-Clinical Patient Transfer

Barratt et al performed a propensity-matched cohort analysis comparing critical care patients who underwent a non-clinical, critical care unit to unit transfer to another hospital with those who were not transferred. Of 308,323 patients admitted to one of 198 adult general critical care units in England and Wales 759 patients underwent a non-clinical transfer within 48 hours of admission to the unit and were compared with 1518 propensity matched patients who were not transferred. There was no difference in the risk of ICU mortality or relative risk of ultimate acute hospital mortality was 1.01 (95% CI 0.87 to 1.16) for the non-clinical transfer group. Transferred patients received on average three additional days of critical care (p <0.001) with the difference in length of acute hospital stay being of borderline significance (p=0.05).

Full Text: Barratt. Effect of non-clinical inter-hospital critical care unit to unit transfer of critically ill patients: a propensity-matched cohort analysis. Critical Care 2012;16:R179


September 2012

Lancet:     Peripheral Cannulation

Rickard et al performed a multicentre, randomised, non-blinded equivalence trial in 3283 patients to test the utility of routine replacement of peripheral cannulae after three days use (n=1690) versus replacement when clinically indicated (n=1593). 5907 catheters were placed, with a mean dwell time for catheters in situ on day 3 was 99 h (SD 54) in the clinically indicated group and 70 h (13) in the routinely replaced group. Phlebitis occurred in 114 of 1593 (7%) patients in the clinically indicated group and in 114 of 1690 (7%) patients in the routine replacement group, an absolute risk difference of 0·41% (95% CI −1·33 to 2·15%), which was within the prespecified 3% equivalence margin. No serious adverse events related to study interventions occurred.

Abstract: Rickard. Routine versus clinically indicated replacement of peripheral intravenous catheters: a randomised controlled equivalence trial. Lancet 2012;380(9847):1066-1074


Lancet:     Cardiac Arrest

Using registry data Goldberger et al evaluated whether the duration of resuscitation attempts varied between hospitals and whether patients at hospitals that attempted resuscitation for longer had higher survival rates than do those at hospitals with shorter durations of resuscitation.  efforts.  64 339 patients with cardiac arrests were identified at 435 US hospitals.  31 198 of 64 339 (48·5%) patients achieved return of spontaneous circulation and 9912 (15·4%) survived to discharge. For patients achieving return of spontaneous circulation, the median duration of resuscitation was 12 min (IQR 6—21) compared with 20 min (14—30) for non-survivors. Compared with patients at hospitals in the quartile with the shortest median resuscitation attempts in non-survivors (16 min [IQR 15—17]), those at hospitals in the quartile with the longest attempts (25 min [25—28]) had a higher likelihood of return of spontaneous circulation (adjusted risk ratio 1·12, 95% CI 1·06—1·18; p<0·0001) and survival to discharge (1·12, 1·02—1·23; 0·021).

Abstract: Goldberger. Duration of resuscitation efforts and survival after in-hospital cardiac arrest: an observational study. Lancet 2012; epublished ahead of print


Lancet:     Surgical Mortality

Pearse et al performed an international cohort study over 7 days to assess outcomes after non-cardiac surgery in Europe. 46 539 consecutive patients aged 16 years and older undergoing inpatient non-cardiac surgery in 498 hospitals across 28 European nations, were recruited. 1855 (4%) died before hospital discharge. 3599 (8%) patients were admitted to critical care after surgery with a median length of stay of 1·2 days (IQR 0·9—3·6). 1358 (73%) patients who died were not admitted to critical care at any stage after surgery. Crude mortality rates varied widely between countries (from 1·2% [95% CI 0·0—3·0] for Iceland to 21·5% [16·9—26·2] for Latvia). After adjustment for confounding variables, important differences remained between countries when compared with the UK, the country with the largest dataset (OR range from 0·44 [95% CI 0·19—1·05; p=0·06] for Finland to 6·92 [2·37—20·27; p=0·0004] for Poland).

Abstract: Pearse. Mortality after surgery in Europe: a 7 day cohort study. Lancet 2012;380(9847):1059-1065


New England Journal of Medicine:     Glycaemic Control

The NICE-SUGAR investigators performed a retrospective analysis of 6026 patients enrolled in the randomized NICE-SUGAR study, to assess the associations between moderate hypoglycaemia (41 to 70 mg/dL; 2.3 to 3.9 mmol/L), severe hypoglycemia (≤40 mg/dL; ≤ 2.2 mmol/L] and death. Data was available for 3010 patients assigned to undergo intensive glycaemic control and 3012 undergoing conventional control. 829 patients (27.5%) in the intensive-control group and 751 (24.9%) in the conventional-control group died (odds ratio for intensive control, 1.14; 95% CI 1.02 to 1.28; P=0.02). The treatment effect did not differ significantly between surgical patients and medical patients (odds ratio for death in the intensive-control group, 1.31 and 1.07, respectively; P=0.10). Severe hypoglycemia was reported in 206 of 3016 patients (6.8%) in the intensive-control group and 15 of 3014 (0.5%) in the conventional-control group (P<0.001). There was no significant difference between the two treatment groups in the median number of days in the ICU (P=0.84) or hospital (P=0.86) or the median number of days of mechanical ventilation (P=0.56) or renal-replacement therapy (P=0.39).

Abstract:  The NICE-SUGAR Study Investigators. Hypoglycemia and Risk of Death in Critically Ill Patients. N Engl J Med 2012;367:1108-1118


New England Journal of Medicine:     Glycaemic Control

Angus et al performed a two-center, prospective, randomized trial in 980 children, 0 to 36 months of age, undergoing cardiac surgery with cardiopulmonary bypass, to test whether tight glycaemic control (80 to 110 mg per deciliter [4.4 to 6.1 mmol per liter]) was superior to standard care. 91% of the children assigned to tight glycemic control received insulin versus 2% assigned to standard care. Intensive insulin therapy was associated with earlier (6 hours vs. 16 hours, P<0.001) and longer proportional time period (50% vs. 33%, P<0.001) with tight glycemic control, but was not associated with a significantly decreased rate of health care–associated infections (8.6 vs. 9.9 per 1000 patient-days, P=0.67) or secondary outcomes. Only 3% of the patients assigned to tight glycemic control had severe hypoglycemia (blood glucose <40 mg per deciliter [2.2 mmol per liter]).

Full Text:  Angus. Tight Glycemic Control versus Standard Care after Pediatric Cardiac Surgery (SPECS Study). N Eng J Med 2012; epublished September 7, 2012

Associated Editorial:

Full Text:  Kavanagh. Glucose in the ICU — Evidence, Guidelines, and Outcomes. N Eng J Med 2012; epublished September 7, 2012


August 2012

New England Journal of Medicine:     Cardiogenic Shock

To test the efficacy of intra-aortic balloon counterpulsation (IABP) in acute myocardial infarction complicated by cardiogenic shock, Thiele et al performed a prospective, open-label, multicenter trial, randomly assigned 600 patients to IABP (n=301) versus no IABP (n=299). The 30 day mortality rate was (39.7%) in the IABP group (119/301) versus 41.3% in the control group (123/299) (relative risk with IABP, 0.96; 95% CI 0.79 to 1.17; P=0.69). There were no significant differences in secondary end points or in process-of-care measures, including the time to hemodynamic stabilization, the length of stay in the intensive care unit, serum lactate levels, the dose and duration of catecholamine therapy, and renal function. Similarly, there were no difference (IABP vs control) in rates of major bleeding  (3.3% vs 4.4%; P=0.51), peripheral ischemic complications (4.3% vs 3.4%, P=0.53), sepsis (15.7% vs 20.5%, P=0.15), and stroke (0.7% vs 1.7%, P=0.28).

Full Text:  Thiele. Intraaortic Balloon Support for Myocardial Infarction with Cardiogenic Shock (IABP-SHOCK II Trial). NEJM epublished ahead of print August 27th 2012


Transfusion:  Age of Transfused Red Cells

Wang et al performed a meta analysis to determine the effect of age of transfused red cells.  21 studies were identified (n=409,966). Older blood was associated with a significantly increased risk of death (odds ratio, 1.16; 95% CI: 1.07-1.24). It was estimated that 97 patients (95% CI: 63-199) would need to be treated with only new blood to save one life. The increased risk was not restricted to a particular type of patient, size of trial, or amount of blood transfused.

Abstract:  Wang. Transfusion of older stored blood and risk of death: a meta-analysis.Transfusion 2012;52(6):1184-95


July 2012

Critical Care Medicine:     Feeding

The ANZICS trial group performed a randomized, controlled trial in 17 ICUs across Australia comparing early nasojejunal (n=92) with nasogastric (n=89) in critically ill patients mechanically ventilated patients with mildly elevated gastric residual volumes and already receiving nasogastric nutrition. There was no difference in the proportion of targeted energy delivered from enteral nutrition between the early nasojejunal nutrition group and the continued nasogastric nutrition group (72% vs 71% respectively, mean difference 1%, 95% CI −3% to 5%, p = .66). Complications such as ventilator-associated pneumonia (20% vs. 21%, p = .94), vomiting, witnessed aspiration, diarrhea, and mortality were similar, although minor gastrointestinal hemorrhage was more common in the early nasojejunal nutrition group (12 [13%] vs. 3 [3%], p = .02).

Abstract:  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


June 2012

New England Journal of Medicine:     Fluid Resuscitation

In a large international multi-centre, randomized controlled trial, Perner et al compared fluid resuscitation with 130/0.4 hydroxyethyl starch with Ringer's acetate in 804 patients with severe sepsis. At 90 days more patients treated with HES had died (201/398, 51%) than with RA (172/400, 43%), (relative risk, 1.17; 95% CI, 1.01 to 1.36; P=0.03). Similarly, at 90 days more patients treated with HES required renal replacement therapy (22% versus 16%; RR 1.35; 95% CI 1.01 to 1.80; P=0.04). More patients treated with HES had severe bleeding, although this failed to reach statistical significance  (10% versus 6%, RR 1.52; 95% CI 0.94 to 2.48; P=0.09).

Full Text:  Perner. Hydroxyethyl Starch 130/0.4 versus Ringer's Acetate in Severe Sepsis. (6S Trial). N Eng J Med 2012


New England Journal of Medicine:     ICU Staffing

In a retrospective cohort analysis, Wallace and colleagues examined the effect of a night-time intensivist on patient outcomes in 65,752 patients admitted to 49 ICUs in 25 American hospitals. In both the primary analysis, and a second confirmatory analysis, the addition of a night-time intensivist to ICUs with  low-intensity daytime staffing was associated with reduced mortality (adjusted odds ratio for death, 0.62; P=0.04), while a night-time intensivist had no effect on mortality in ICUs with high-intensity daytime staffing (odds ratio, 1.08; P=0.78).

Full Text: Wallace. Nighttime Intensivist Staffing and Mortality among Critically Ill Patients. N Engl J Med 2012; 366:2093-2101


New England Journal of Medicine:     Activated Protein C

Ranieri and colleagues performed a randomized, double-blind, placebo-controlled, multicenter trial, investigating the efficacy of activated protein C in 1697 patients with septic shock. No difference was seen in mortality at 28 days {(APC: 223 of 846 patients (26.4%) vs placebo: 202 of 834 (24.2%) (relative risk with APC 1.09; 95% CI, 0.92 to 1.28; P=0.31)} or at 90 days {APC: 287 of 842 patients (34.1%) vs placebo: 269 of 822 (32.7%) (relative risk, 1.04; 95% CI, 0.90 to 1.19; P=0.56)}. Similarly, there were no differences in subgroups, including those with increased risk of death, or in the incidence of serious bleeding.

Abstract: Ranieri. Drotrecogin Alfa (Activated) in Adults with Septic Shock ( PROWESS-SHOCK Study). N Engl J Med 2012;366:2055-206


Lancet:     Subarachnoid Haemorrhage

In an international multi-centre randomised, placebo-controlled trial of 1204 patients within 4 days of onset of SAH, the addition of 64 mmol/day of MgSO4 intravenously had no effect on the primary outcome of a score of 4—5 on the modified Rankin Scale—3 months after subarachnoid haemorrhage, or death {158 patients (26·2%)  magnesium group vs 151 (25·3%)  placebo group (RR 1·03, 95% CI 0·85—1·25).

Abstract: Dorhout Mees. Magnesium for aneurysmal subarachnoid haemorrhage (MASH-2): a randomised placebo-controlled trial. Lancet 2012; epublished ahead of print


May 2012

JAMA:     Berlin Definition of ARDS

The recently produced Berlin Definition of ARDS was empirically evaluated with data from 4188 patients with ARDS from 4 multicenter clinical data sets and 269 patients with ARDS from 3 single-center data sets. Using the Berlin Definition, stages of mild (PaO2/FiO2 > 200 mmHg), moderate (PaO2/FiO2 > 100 mmHg), and severe (PaO2/FiO2 < 100 mmHg) ARDS were associated with increased mortality (mild: 27%; 95% CI, 24%-30%), (moderate: 32%; 95% CI, 29%-34%), (severe: 45%; 95% CI, 42%-48%) respectively, P < .001. Also the new definition demonstrated increased median duration of mechanical ventilation in survivors (mild: 5 days; IQR, 2-11) (moderate: 7 days; IQR, 4-14), (severe: 9 days; IQR, 5-17) respectively, P < .001. Although both were poor predictors of mortality, the final Berlin Definition had better predictive validity for mortality than the American-European Consensus Conference Criteria, with an area under the receiver operating curve of 0.577 (95% CI, 0.561-0.593) vs 0.536 (95% CI, 0.520-0.553), P < .001.

Full Text: The ARDS Definition Task Force. Acute Respiratory Distress Syndrome. The Berlin Definition. JAMA 2012; epublished ahead of print


JAMA:     Severe Sepsis

In a randomized, open-label, parallel-group trial of 600 patients with severe sepsis or septic shock, therapy with meropenam (1 g 8 hourly) plus moxifloxacin (400 mg daily) was not superior to meropenam alone for either severity of organ failure or mortality at 28 or 90 days.

Full Text: Brunkhorst. Effect of Empirical Treatment With Moxifloxacin and Meropenem vs Meropenem on Sepsis-Related Organ Dysfunction in Patients With Severe SepsisA Randomized Trial. JAMA 2012;epublished ahead of print

Lancet:     Stroke Thrombolysis

Wardlaw et al performed a systematic review and meta analysis, comprising 12 trials containing 7012 patients, examining the effects of recombinant tissue plasminogen activator administered within 6 hours of the onset of ischaemic stroke. rt-PA  increased the odds of being alive and independent (modified Rankin Scale, mRS 0—2) at final follow-up (1611/3483 [46·3%] vs 1434/3404 [42·1%], OR 1·17, 95% CI 1·06—1·29; p=0·001), absolute increase of 42 (19—66) per 1000 people treated, and favourable outcome (mRS 0—1) absolute increase of 55 (95% CI 33—77) per 1000.

Abstract: Wardlaw. Recombinant tissue plasminogen activator for acute ischaemic stroke: an updated systematic review and meta-analysis. Lancet 2012; epublished ahead of print


Lancet:     Stroke Thrombolysis

The IST-3 Collaborative group performed an international, multicentre, randomised, open-treatment trial, comparing 0·9 mg/kg intravenous recombinant tissue plasminogen activator (rt-PA) with control, in 3035 patients within 6 hours of acute ischaemic stroke. An increase in early deaths and complications was offset by a late decrease in deaths and improved functional outcomes, such that by 6 months an adjusted odds ratio ([OR] 1·13, 95% CI 0·95—1·35, p=0·181) was not significantly different between the two groups. However, an ordinal analysis showed a significant shift in functional outcome scores (common OR 1·27 (95% CI 1·10—1·47, p=0·001).

Full Text: The IST-3 collaborative group. The benefits and harms of intravenous thrombolysis with recombinant tissue plasminogen activator within 6 h of acute ischaemic stroke (the third international stroke trial [IST-3]): a randomised controlled trial. Lancet 2012;epublished ahead of print     (free registration required)


JAMA:     GKI Infusions in Out-of-Hospital Acute Coronary Syndromes

In a randomized, placebo-controlled, double-blind effectiveness study in 13 US cities, Selker et al compared the effectivness of glucose-insulin-potassium infusion (GIK) (n=411) versus placebo (n=460) in out-of-hospital acute coronary syndromes. There was no difference in the rate of progression to MI among patients who received GIK (odds ratio [OR], 0.88; 95% CI, 0.66-1.13; P = .28); or 30 day mortality (hazard ratio [HR], 0.72; 95% CI, 0.40-1.29; P = .27). The composite of cardiac arrest or in-hospital mortality occurred in 4.4% with GIK vs 8.7% with placebo (OR, 0.48; 95% CI, 0.27-0.85; P = .01). Among patients with ST-segment elevation, there was no difference in progression to MI (OR, 0.74; 95% CI, 0.40-1.38; P = .34); or 30-day mortality (HR, 0.63; 95% CI, 0.27-1.49; P = .29). The composite outcome of cardiac arrest or in-hospital mortality was 6.1% with GIK vs 14.4% with placebo (OR, 0.39; 95% CI, 0.18-0.82; P = .01). Serious adverse events did not differ between the 2 groups (P = .26).

Abstract: Selker. Out-of-Hospital Administration of Intravenous Glucose-Insulin-Potassium in Patients With Suspected Acute Coronary Syndromes. The IMMEDIATE Randomized Controlled Trial. JAMA 2012;307(1):1925-1933


April 2012

Nephrology Dialysis & Transplantation:     Renal Replacement Therapy

In a prospective, randomized, controlled single-centre study, Skofic and colleagues compared mortality and recovery of renal function between intermittent high-volume predilution on-line haemofiltration (HF) and standard intermittent haemodialysis (HD) in 273 critically ill adult patients with acute kidney injury. All-cause mortality by Day 60 was 65.0% in the HF group and 65.5% in the HD group (hazard ratio, 0.98; 95% CI, 0.71–1.33; P = 0.87). There were also no significant differences between the two groups in 30-day and in-hospital all-cause mortality or recovery of kidney function. Time to kidney function recovery and the number of required dialysis procedures were similar between the HF and the HD subgroup of patients with in-hospital recovery of kidney function.

Full Text: Skofic. Intermittent high-volume predilution on-line haemofiltration versus standard intermittent haemodialysis in critically ill patients with acute kidney injury: a prospective randomized study.Nephrol Dial Transplant 2012 epublished ahead of print


JAMA:    Pre-Hospital Trauma Transfer

To assess the association between the use of helicopter vs ground services and survival among adults with serious traumatic injuries, Galvagno et al performed a retrospective cohort study utilizing the 2007-2009 versions of the American College of Surgeons National Trauma Data Bank. A total of 61 909 patients were transported by helicopter and 161 566 patients were transported by ground. Overall, 7813 patients (12.6%) transported by helicopter died compared with 17 775 patients (11%) transported by ground services. In the propensity score–matched multivariable regression model, for patients transported to level I trauma centers, helicopter transport was associated with an improved odds of survival compared with ground transport (OR, 1.16; 95% CI, 1.14-1.17; P < .001; absolute risk reduction [ARR], 1.5%). For patients transported to level II trauma centers, helicopter transport was associated with an improved odds of survival (OR, 1.15; 95% CI, 1.13-1.17; P < .001; ARR, 1.4%). A greater proportion (18.2%) of those transported to level I trauma centers by helicopter were discharged to rehabilitation compared with 12.7% transported by ground services (P < .001), and 9.3% transported by helicopter were discharged to intermediate facilities compared with 6.5% by ground services (P < .001).

Full Text: Galvagno. Association Between Helicopter vs Ground Emergency Medical Services and Survival for Adults With Major Trauma. JAMA 2012; 307:1602-1610


American Journal of respiratory and Critical Care Medicine:     ARDS

Mikkelsen et al performed a telephone survey of 213 of the 406 survivors from the ARDSnet FACTT trial, to determine neuropsychological function at 2 and 12 months post hospital discharge. Memory, verbal fluency and executive function were impaired in 13% (12/92), 16% (15/96), and 49% (37/76) of long-term survivors. Long-term cognitive impairment was present in 41 of the 75 (55%) survivors who completed cognitive testing. Depression, post-traumatic stress disorder, or anxiety was present in 36% (37/102), 39% (40/102), and 62% (63/102) of long-term survivors. Enrollment in a conservative fluid-management strategy (p=0.005) was associated with cognitive impairment and lower partial pressure of arterial oxygen during the trial was associated with cognitive (p=0.02) and psychiatric impairment (p=0.02).

Abstract: Mikkelsen. The ARDS Cognitive Outcomes Study (ACOS): Long-Term Neuropsychological Function in Acute Lung Injury Survivors.Am. J. Respir. Crit. Care Med 2012; epublished ahead of print


Clinical Infectious Diseases:     Tigecycline

Prasad et al performed a meta analysis of 10 published and 3 unpublished studies (N = 7434) examining excess deaths and non-cure rates for both approved and non-approved indications for tigecycline. Across randomized controlled trials, tigecycline was associated with increased mortality [risk difference (RD) 0.7%; 95% CI (0.1% to 1.2%), p = 0.01] and non-cure rates [RD 2.9%; 95% CI (0.6% to 5.2%), p = 0.01]. Effects were not isolated to one type of infection or comparator antibiotic regimen and the impact on survival remained significant when limited to trials of approved indications (I2 = 0%; RD 0.6%, p = 0.04). A pooled analysis of the five trials completed by early 2005 before tigecycline was approved would have demonstrated a similar harmful effect of tigecycline on survival (I2 = 0%; RD 0.7%, p = 0.06).

Abstract: Prasad. Excess Deaths Associated with Tigecycline After Approval Based on Non-Inferiority Trials. Clin Infect Dis 2012; epublished ahead of print


Gastroenterology:     Prometheus

Kribben et al performed a randomised controlled trial comparing fractionated plasma seperation and adsorption (Prometheus) plus standard medical therapy (n=77) with standard medical therapy alone (n=68). In an intention-to-treat analysis, the probabilities of survival on day 28 were 66% in the FPSA group and 63% in the SMT group (P = .70); on day 90, they were 47% and 38%, respectively (P = .35). Serum bilirubin level decreased significantly in the FPSA group but not in the SMT group. Factors independently associated with poor prognosis were high SOFA score, bleeding, female sex, spontaneous bacterial peritonitis, intermediate increases in serum creatinine concentration, and combination of alcoholic and viral etiology of liver disease. There were no differences between the 2 groups in the incidence of side effects.

Abstract: Kribben. Effects of Fractionated Plasma Separation and Adsorption on Survival in Patients With Acute-on-Chronic Liver Failure (HELIOS study). Gastroenterology 2012;142(4)782-789

Associated Editorial:  Leckie. Albumin Regeneration for Extracorporeal Liver Support Using Prometheus: A Step in the Right Direction. Gastroenterology 2012;142(4):690-692


British Medical Journal:     Mechanical Ventilation in ARDS

Needham and colleagues performed an observational study evaluating 2 year outcomes in 485 consecutive mechanically ventilated patients with acute lung injury. They found that after adjusting for the total duration of ventilation and other relevant covariates, each additional ventilator setting adherent to lung protective ventilation was associated with a 3% decrease in the risk of mortality over two years (hazard ratio 0.97, 95% CI 0.95 to 0.99, P=0.002). Compared with no adherence, the estimated absolute risk reduction in two year mortality for a prototypical patient with 50% adherence to lung protective ventilation was 4.0% (0.8% to 7.2%, P=0.012) and with 100% adherence was 7.8% (1.6% to 14.0%, P=0.011).

Full Text: Needham. Lung protective mechanical ventilation and two year survival in patients with acute lung injury: prospective cohort study. BMJ 2012; 344


New England Journal of Medicine:     Pulmonary Embolism

In a randomized, open-label, event-driven, noninferiority trial involving 4832 patients who had acute symptomatic pulmonary embolism with or without deep-vein thrombosis,  rivaroxaban (15 mg twice daily for 3 weeks, followed by 20 mg once daily) was compared with standard therapy with enoxaparin followed by an adjusted-dose vitamin K antagonist for 3, 6, or 12 months. Rivaroxaban was noninferior to standard therapy (noninferiority margin, 2.0; P=0.003) for the primary outcome of symptomatic recurrance, with 50 events in the rivaroxaban group (2.1%) versus 44 events in the standard-therapy group (1.8%) (hazard ratio, 1.12; 95% CI, 0.75 to 1.68). The principal safety outcome occurred in 10.3% of patients in the rivaroxaban group and 11.4% of those in the standard-therapy group (hazard ratio, 0.90; 95% CI, 0.76 to 1.07; P=0.23). Major bleeding was observed in 26 patients (1.1%) in the rivaroxaban group and 52 patients (2.2%) in the standard-therapy group (hazard ratio, 0.49; 95% CI, 0.31 to 0.79; P=0.003). Rates of other adverse events were similar in the two groups.

Abstract: The EINSTEIN–PE Investigators. Oral Rivaroxaban for the Treatment of Symptomatic Pulmonary Embolism. N Engl J Med 2012; 366:1287-1297


March 2012

Resuscitation:     Vasopressors in Cardiac Arrest

In a systematic review of 53 studies investigating the use of vasopressors in cardiac arrest, Larabee determined that, compared to placebo, adrenaline improved short term survival, but not long term survival. Similarly, high dose adrenaline achieved a better short term outcome, but not long term outcome, than standard dose adrenaline. Vasopressin was equivalent to adrenaline.

Abstract: Larabee. Vasopressors in Cardiac Arrest: A Systematic Review. Resuscitation 2012;epubished ahead of print


JAMA:     Dexmedetomidine for Sedation in ICU

Jakob and colleagues report the results of two phase 3 international randomized controlled trials evaluating non-inferiority of dexmedetomidine with either midazolam (MIDEX study) or with propofol (PRODEX), for sedation in the ICU.

In the MIDEX study (dexmedetomidine: n = 249, midazolam: n = 251), there was no difference in the time at target sedation {Dex/Mid ratio 1.07 (95% CI, 0.97-1.18)}, although duration of ventilation was shorter {Dex: 123 hours [IQR, 67-337] vs Mid: 164 hours [IQR, 92-380], P = .03}. Patient interaction improved with dexmedetomidine, but there were no differences in length of ICU or hospital stay, or mortality. Dexmedetomidine was associated with more hypotension (51/247 [20.6%] vs 29/250 [11.6%]; P = .007) and bradycardia (35/247 [14.2%] vs 13/250 [5.2%]; P < .001).

In the PRODEX study (dexmedetomidine: n=223, propofol: n=214,), there was no difference in the time spent at target sedation {Dex/Pro ratio 1.00 (95% CI, 0.92-1.08}, or duration of mechanical ventilation {Dex: 97 hours [IQR, 45-257] vs Pro: 118 hours [IQR, 48-327]; P = .24}. Patient interaction was again improved with dexmedetomidine, but similarly, there were no differences in length of ICU or hospital stay, or mortality.

Abstract: Jakob. Dexmedetomidine vs Midazolam or Propofol for Sedation During Prolonged Mechanical Ventilation: Two Randomized Controlled Trials. JAMA 2012;307(11):1151-1160


JAMA:     Adrenaline in Out-Of-Hospital Cardiac Arrest 

Hagihara et al report the association of adrenaline with outcome in out-of-hospital cardiac arrest from 417,188 events recorded in a prospective, nonrandomized, observational study. Return of spontaneous circulation before hospital arrival was observed in 2,786 of 15,030 patients (18.5%) in the adrenaline group and 23,042 of 402,158 patients (5.7%) in the non-adrenaline group (P < .001); it was observed in 2,446 (18.3%) and 1,400 (10.5%) of 13,401 propensity-matched patients, respectively (P < .001). In the total sample, the numbers of patients with 1-month survival and survival with good neurological outcomes, respectively, were 805 (5.4%), 205 (1.4%), and 211 (1.4%) with adrenaline and 18,906 (4.7%), 8,903 (2.2%), and 8,831 (2.2%) without adrenaline (all P <.001). Corresponding numbers in propensity-matched patients were 687 (5.1%), 173 (1.3%), and 178 (1.3%) with adrenaline and 944 (7.0%), 413 (3.1%), and 410 (3.1%) without adrenaline (all P <.001). The authors conclude that the use of prehospital adrenaline was significantly associated with increased chance of return of spontaneous circulation before hospital arrival but decreased chance of survival and good functional outcomes 1 month after the event.

Abstract: Hagihara. Prehospital Epinephrine Use and Survival Among Patients With Out-of-Hospital Cardiac Arrest. JAMA 2012;307(11):1161-1168


New England Journal of Medicine - Thrombolysis for Stroke

In a phase 2B study, Parsons and colleagues compared tenecteplase (0.1 or 0.25 mg/kg) with alteplase (0.9mg/kg) for thrombolysis in 3 groups of 25 patients with acute cerebral infarction of 6 hours duration or or less. Both tenecteplase groups had greater reperfusion (P=0.004) and clinical improvement (P<0.001) at 24 hours than the alteplase group, with the higher tenecteplase dose being superior to the lower dose.

Abstract: Parsons. A Randomized Trial of Tenecteplase versus Alteplase for Acute Ischemic Stroke. N Engl J Med 2012; 366:1099-1107

JAMA:     Acute Pancreatitis

In a prospective, randomized controlled trial, Bakker et al compared outcomes between endoscopic or surgical necrosectomy in 22 patients (20 evaluated) with acute pancreatitis. Endoscopic transgastric necrosectomy reduced the postprocedural IL-6 levels compared with surgical necrosectomy (P = .004). The composite clinical end point occurred less often after endoscopic necrosectomy (20% vs 80%; risk difference [RD], 0.60; 95% CI, 0.16-0.80; P = .03). Endoscopic necrosectomy did not cause new-onset multiple organ failure (0% vs 50%, RD, 0.50; 95% CI, 0.12-0.76; P = .03) and reduced the number of pancreatic fistulas (10% vs 70%; RD, 0.60; 95% CI, 0.17-0.81; P = .02).

Abstract: Bakker. Endoscopic Transgastric vs Surgical Necrosectomy for Infected Necrotizing Pancreatitis: A Randomized Trial. JAMA 2012;307(10):1053-106


Archives of Internal Medicine:     ICU Bed Availability & Outcomes

Stelfox et al evaluated the effect of ICU bed availability on processes and outcomes of care in 3494 hospitalized patients with sudden clinical deterioration over a 2 year period. Reduced ICU bed availability was associated with a decreased likelihood of patient admission within 2 hours of medical emergency team activation (P = .03) and with an increased likelihood of change in patient goals of care (P < .01). Patients with sudden clinical deterioration when no ICU beds were available were 33.0% (95% CI, –5.1% to 57.3%) less likely to be admitted to the ICU and 89.6% (95% CI, 24.9% to 188.0%) more likely to have their goals of care changed compared with when more than 2 ICU beds were available. Hospital mortality did not vary significantly by ICU bed availability (P = .82).

Abstract: Stelfox. Intensive Care Unit Bed Availability and Outcomes for Hospitalized Patients With Sudden Clinical Deterioration. Arch Intern Med 2012;epublished ahead of print


Shock:     Intra-Aortic Ballon Counterpulsation

In a single-centre, prospective, randomized controlled trial, Prodzinsky et al evaluated the haemodynamic effects of intra-aortic ballon counterpulsation in 40 subjects with cardiogenic shock after myocardial infarction. Although there were  improvements in cardiac output (4.8 ± 0.5 to 6.0 ± 0.5 L/min), systemic vascular resistance (926 ± 73 to 769 ± 101 dyn · s−1 · cm−5), and the prognosis-validated cardiac power output (0.78 ± 0.06 to 1.01 ± 0.2 W) within the IABP group, this treatment did not result in a significant hemodynamic improvement compared with medical therapy alone.

Abstract: Prondzinsky. Hemodynamic Effects of Intra-aortic Balloon Counterpulsation in Patients With Acute Myocardial Infarction Complicated by Cardiogenic Shock: The Prospective, Randomized IABP Shock Trial. Shock 2012;37(4):378–384


British Journal of Anaesthesia:     Rocuronium vs Suxamethonium

In a randomized controlled trial in 61 subjects (55 evaluated), Sørensen et al compared the speed to return of spontaneous ventilation after induction of general anaesthesia and tracheal intubation, between rocuronium 1mg/kg followed by suggamadex 16 mg/kg after intubation, or suxamethonium 1mg/kg. The use of Rocuronium/Suggamadex allowed a significantly faster return to both spontaneous ventilation (median time 216 s v 406 s; P = 0.002), and first twitch in train-of-four (T1 90%) (168 s v 518 s; P < 0.0001). Intubation conditions and time to tracheal intubation were not significantly different.

Abstract: Sørensen. Rapid sequence induction and intubation with rocuronium–sugammadex compared with succinylcholine: a randomized trial. Br J Anaesth 2012;108(4):682-689


Critical Care:     Fever Control 

Egi and colleagures performed a prospective observational study to investigate the association of fever and the use of antipyretic treatments with mortality in 1,425 critically ill patients without neurological injury. We included 1,425 consecutive adult critically ill patients (without neurological injury) requiring >48 hours intensive care admitted in twenty-five ICUs. Body temperature was recorded 63,441 times, and antipyretic treatment was given 4,863 times to 737 patients (51.7%). Treatment with NSAIDs or acetaminophen independently increased 28-day mortality for septic patients (adjusted odds ratio: NSAIDs: 2.61, p=0.028, acetaminophen: 2.05, p=0.01), but not for non-septic patients (adjusted odds ratio: NSAIDs: 0.22, p=0.15, acetaminophen: 0.58, p=0.63). Physical cooling was not associated with mortality in either group. Relative to the temperature reference range (36.5 -37.4 C), maximum temperature (> 39.4 C) increased risk of 28-day mortality in septic patients (adjusted odds ratio 8.14, p=0.01), but not in non-septic patients (adjusted odds ratio 0.47, p=0.11).

Abstract: Egi. Association of body temperature and antipyretic treatments with mortality of critically ill patients with and without sepsis: multi-centered prospective observational study. Critical Care 2012, 16:R33


Nephrology Dialysis Transplantation:     Renal Replacement Therapy

Zhang and colleagues performed a single-centre, randomized control trial, comparing high-volume hemofiltration (50 mL/kg/h, HVHF) or extra high-volume hemofiltration (85 mL/kg/h, EHVHF) in 280 patients with sepsis and acute kidney injury. The two groups had similar baseline characteristics and received treatment for an average of 9.38 days (EHVHF group) and 8.88 days (HVHF group). There were no significant differences between the groups in number of deaths at 28, 60 or 90 days. There were also no differences between the groups in renal outcome of survivors at 90 days.

Abstract: Zhang. Effect of the intensity of continuous renal replacement therapy in patients with sepsis and acute kidney injury: a single-centre randomized clinical trial. Nephrol. Dial. Transplant. (2012)27 (3): 967-973.


Nephrology Dialysis Transplantation:     Renal Replacement Therapy

Schneider and colleagues evaluated the characteristics and outcome of 90 patients with severe (RIFLE-F) acute kidney injury who did not receive renal replacement therapy (RRT) in comparison with 105 patients who did receive RRT. Both groups were similar in terms of age, gender and ward of origin. However, patients not receiving RRT had a shorter median ICU stay (2.7 v 7.9 days; P < 0.001), required less mechanical ventilation (56.2 v 70%; P < 0.05) and had a lower mean Acute Physiology and Chronic Health Evaluation III score (82.7 v 86.7; P < 0.05). The two main reasons these patients did not receive RRT were limitations of medical therapy (LOMT) orders in 41 (39%) cases and expected renal functional improvement in 59 (56.2%). Mortality in no-RRT patients was 58.1% compared with 55.5% in the RRT group (P = 0.72). After exclusion of LOMT patients, the mortality of the no-RRT group, although lower than that of the RRT group, remained high (30.5 v 55%; P < 0.001). Most of these deaths occurred after ICU discharge and appeared secondary to underlying chronic diseases or recurrence of the initial insult.

Abstract: Schneider. Severe acute kidney injury not treated with renal replacement therapy: characteristics and outcome. Nephrol. Dial. Transplant 2012;27(3):947-952


Annals of Internal Medicine:     Influenza

In a systematic review and meta-analysis, Chartrand investigated the accuracy of rapid influenza diagnostic tests (RIDTs) in 159 studies that evaluated 26 different RIDTs. 35% were conducted during the H1N1 pandemic. The pooled sensitivity and specificity were 62.3% (95% CI, 57.9% - 66.6%) and 98.2% (CI, 97.5% - 98.7%), respectively. The positive and negative likelihood ratios were 34.5 (CI, 23.8 - 45.2) and 0.38 (CI, 0.34 - 0.43), respectively. Sensitivity estimates were highly heterogeneous, which was partially explained by lower sensitivity in adults (53.9% [CI, 47.9% to 59.8%]) than in children (66.6% [CI, 61.6% to 71.7%]) and a higher sensitivity for influenza A (64.6% [CI, 59.0% to 70.1%) than for influenza B (52.2% [CI, 45.0% to 59.3%). The stdies were limited by an inability to determine specimen type and duration of influenza symptoms, on diagnostic accuracy. The authors conclude influenza can be ruled in but not ruled out through the use of RIDTs.

Abstract: Chartrand. Accuracy of Rapid Influenza Diagnostic Tests - A Meta-Analysis. Ann Intern Med 2012;epublished ahead of print


Annals of Internal Medicine:     Influenza

In a systematic review and meta-analysis of 74 studies investigating the efficacy of antivirals for the treatment of influenza, Hsu and colleagues found that, with adjustment for confounders, in high-risk populations, oral oseltamivir may reduce mortality (OR 0.23 [95% CI, 0.13 to 0.43];  hospitalization (OR 0.75 [CI, 0.66 to 0.89]; and duration of symptoms (33 hours [CI, 21 to 45 hours]; compared with no treatment, all of which was based on low quality evidence. Earlier treatment with oseltamivir was generally associated with better outcomes. Inhaled zanamivir may lead to shorter symptom duration (23 hours [CI, 17 to 28 hours]; moderate-quality evidence) and fewer hospitalizations (OR 0.66 [CI, 0.37 to 1.18]) but more complications than no treatment. Direct comparison of oral oseltamivir and inhaled zanamivir suggests no important differences in key outcomes. Data from 1 study suggests that oral amantadine may reduce mortality and pneumonia associated with influenza A. 

Abstract : Hsu. Antivirals for Treatment of Influenza: A Systematic Review and Meta-analysis of Observational Studies. Ann Intern Med 2012;epublished ahead of print


New England Journal of Medicine:     Traumatic Brain Injury

In a placebo controlled trial in 184 patients in a vegetative or minimally conscious state 4 to 16 weeks after traumatic brain injury, Giacino and colleagues investigated the effects of amantadine on the rate of functional recovery using the Disability Rating Scale. During a 4 week treatment period, the rate of recovery was significantly faster with amantidine, although this improved recovery was lost by 6 weeks, 2 weeks after stopping this therapy.

Abstract: Giacino. Placebo-Controlled Trial of Amantadine for Severe Traumatic Brain Injury. N Engl J Med 2012; 366:819-826


February 2012

Emergency Medicine Australasia:     CT PanScan in Trauma

To examine the utility of a panscan in blunt trauma, Asha and colleagues, in an before (n=656) and after (n=624) the introduction of a panscan protocol,  compared the proportion of patients exposed to a radiation dose in excess of 20 mSv, and the incidence of missed injuries. The proportion of patients exposed to a radiation dose >20 mSv increased by 8% (95% CI: 4–12), which equated to one extra person being exposed to >20 mSv for every 13 patients treated after the introduction of the protocol. The odds of receiving a radiation dose >20 mSv after the introduction of the protocol compared with the odds before were increased across all subgroups. There were six missed injuries before and four after.

Full text: Asha. Comparison of radiation exposure of trauma patients from diagnostic radiology procedures before and after the introduction of a panscan protocol. Emergency Medicine Australasia 2012;24(1):43-51


Resuscitation:     Cardiac Arrest

In a randomised, double-blind, multi-centre, parallel-design clinical trial in four adult hospitals, Hock et al compared an initial dose of either adrenaline (1 mg) or vasopressin (40 IU), followed by current standard cardiac arrest management, in 727 patients in cardiac arrest in the Emergency Department. Both groups had comparable baselines. Eight participants (2.3%) from adrenaline and 11 (2.9%) from vasopressin group survived to hospital discharge with no significant difference between groups (p=0.27, RR=1.72, 95% CI=0.65 to 4.51). Sub-group analysis suggested improved outcomes for vasopressin in participants with prolonged arrest times.

Abstract: Hock. A Randomised, Double-Blind, Multi-Centre Trial Comparing Vasopressin and Adrenaline in Patients with Cardiac Arrest Presenting to or in the Emergency Department. Resuscitation 2012; epublished ahead of print


American Journal of Respiratory and Critical Care Medicine:     Fever Supression in Septic Shock

In a multicenter randomized controlled trial, Schortgen et al compared fever supression with external cooling (n=101) to achieve normothermia (36.5-37°C) for 48 hours with no external cooling (n=99) in critically ill febrile patients with septic shock. Body temperature was significantly lower in the cooling group after 2 hours of treatment (36.8±0.7 vs. 38.4±1.1°C, P<0.01). A 50% vasopressor dose decrease was more common with external cooling after 12 hours of treatment (54% vs. 20%; 95% CI: -46 to -21; P<0.001) but not at 48 hours. Shock reversal during the ICU stay was significantly more common with cooling (86% vs. 73%; 95%CI: 2 to 25; P=0.021). Day-14 mortality was significantly lower in the cooling group (19% vs. 34%; 95%CI: -28 to -4; P=0.013).

Abstract: Schortgen. Fever Control Using External Cooling in Septic Shock: a Randomized Controlled Trial. J Respir Crit Care Med; epublished 23 February 2012


Resuscitation:     Out-of-Hospital Cardiac Arrest

Brei and colleagues conducted a pre-hospital randomized study with the Emergency Medical Service of Bonn, Germany, comparing hypertonic saline {2mlkg−1 7.2% NaCl with 6% hydroxyethyl starch 200,000/0.5 (HES)} with HES in 203 out-of-hospital cardiac arrest patients. Hypertonic saline was associated with a brief rise in serum Na from 162±36mmoll−1 at 10min after infusion  to near normal (144±6mmoll−1) at hospital admission. Survival to hospital admission and hospital discharge was similar in both groups (50/100 7.2% NaCl vs. 49/103 HES for hospital admission, 23/100 HHS vs. 22/103 HES for hospital discharge). There was a small improvement in neurological outcome at discharge in survivors who received 7.2% NaCl  (cerebral performance category 1 or 2; 13/100 7.2% NaCl vs. 5/100 HES, p<0.05, odds-ratio 2.9, 95% CI 1.004–8.5).

Abstract: Brei. Randomised study of hypertonic saline infusion during resuscitation from out-of-hospital cardiac arrest. Resuscitation 2012;83(3):347-352


Archives of Surgery:     Tranexamic Acid in Combat Trauma

In a retrospective study of 896 consecutive admissions of US and UK soldiers with combat injuries in Afganistan, who received at least 1 unit of red cells, Morrison compared the outcomes between those who received tranexamic acid (n=293) and those who did not (n=603).  Those receiving tranexamic acid had lower unadjusted mortality (17.4% vs 23.9%; P = .03) despite being more severely injured (Injury Severity Score, 25.2 [16.6] vs 22.5 [18.5]; P < .001). This benefit was greatest in the group of patients who received massive transfusion (14.4% vs 28.1%; P = .004), where tranexamic acid was also independently associated with survival (odds ratio = 7.228; 95% CI, 3.016-17.322) and less coagulopathy (P = 0.003).

Abstract: Morrison. Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study. Arch Surg 2012;147(2):113-119


Critical Care Medicine:     Vasopressors in Septic Shock

In a systematic review and meta analysis, De Backer and colleagues compared the use of noradrenaline with dopamine in the management of septic shock. Five observational studies (1,360 patients) and six randomized studies (1,408 patients) were identified (noradrenaline, n=1474; dopamine, n=1294). In the observational studies, after exclusion of a single study responsible for significant heterogeneity, the use of dopamine was associated with increased risk of death (RR 1.23; 95% CI 1.05–1.43; p < 0.01). The randomized trials, which did not demonstrate heterogenetity or publication bias, also associated dopamine use with increased risk of death (RR 1.12; 95% CI 1.01–1.20; p = 0.035); and in two studies reporting arrthymias, dopamine again was associated with increased risk of arrthymias (RR 2.34, 95% CI 1.46-3.77; p=0.001).

Abstract: De Backer. Dopamine versus norepinephrine in the treatment of septic shock: A meta-analysis. Critical Care Med 2012;40(3):725-730


Critical Care:     Delirium

In a two-centre prospective, randomized, double-blind, placebo-controlled trial, Wang and colleagues investigated the efficacy and safety of intravenous haloperidol for delirium prevention in 457 patients critically ill elderly patients after noncardiac surgery. Subjects were randomized at admission to ICU to receive IV bolus 0.5mg haloperidol, followed by continuous infusion at 0.1mg/h for 12 hours (n=229), or placebo (n=228). The incidence of delirium within the first 7 days was 15.3% (35/229) in the haloperidol group and 23.2% (53/228) in the control group (p = 0.031). The mean time to onset of delirium and the mean number of delirium-free days were significantly longer (6.2 days [95% CI 5.9−6.4] vs. 5.7 days [95% CI 5.4−6.0]; p = 0.021; and 6.8 ± 0.5 days vs. 6.7 ± 0.8 days; p = 0.027, respectively) with haloperidol therapy. Similarly, the median length of ICU stay was significantly shorter (21.3 hrs [95% CI 20.3−22.2] vs. 23.0 hrs [95% CI 20.9–25.1]; p = 0.024) in the haloperidol group.  All-cause 28-day mortality did not differ between the two groups (0.9% [2/229] vs. 2.6% [6/228]; p = 0.175). There were no drug-related side effects.

Abstract: Wang. Haloperidol prophylaxis decreases delirium incidence in elderly patients after noncardiac surgery: A randomized controlled trial. Critical Care Med 2012;40(3):731–739


Clinical Infectious Disease:     Linezolid in MRSA Nosocomial Pneumonia

In a prospective, double-blind, controlled, multicenter trial, Wunderink compared intravenous linezolid (600 mg every 12 hours) with vancomycin (15 mg/kg every 12 hours) in 1184 patients with hospital-acquired or healthcare–associated MRSA pneumonia. Both all-cause 60-day mortality (linezolid, 15.7%; vancomycin, 17.0%) and the incidence of adverse events, were similar between groups. Nephrotoxicity occurred more frequently with vancomycin (18.2% vs 8.4%). At the end of the study period, in a subgroup evaluation, in patients evaluated by protocol, 95 of 165 (57.6%) linezolid-treated patients and 81 of 174 (46.6%) vancomycin-treated patients achieved clinical success (95% CI: 0.5%–21.6%; P = .042).

Abstract: Wunderink. Linezolid in Methicillin-Resistant Staphylococcus aureus Nosocomial Pneumonia: A Randomized, Controlled Study. Clin Infect Dis 2012 published 2 February 2012


European Journal of Heart Failure:     Vitamin D Supplementation in Heart Failure

Gotsman et al evaluated the effects of vitamin D deficiency and supplementation in heart failure. In a health maintenance organization, 3009 patients with heart failure were compared with the remaining 46,825 subjects in the organization. Patients with heart failure had a lower median vitamin D level: 36.9 nmol/L (interquartile range 23.2–55.9) vs. 40.7 nmol/L (26.7–56.9), P < 0.00001. The percentage of patients with vitamin D deficiency [vitamin )D <25 nmol/L] was higher in patients with HF compared with the control group (28% vs. 22%, P < 0.00001). Only 8.8% of the heart failure patients had optimal vitamin D levels (≥75 nmol/L). Vitamin D deficiency was an independent predictor of mortality in both patients with HF [hazard ratio 1.52, 95% CI 1.21–1.92, P < 0.001] and the control group (HR 1.91, 95% CI 1.48–2.46, P < 0.00001). Vitamin D supplementation was independently associated with reduced mortality in HF patients (HR 0.68, 95% CI 0.54–0.85, P < 0.0001).

Abstract: Gotsman. Vitamin D deficiency is a predictor of reduced survival in patients with heart failure; vitamin D supplementation improves outcome. Eur J Heart Fail 2012 published 3 February 2012


American Journal of Respiratory and Critical Care Medicine:     Red Cell Transfusion

Kor et al report a double-blind, randomized, clinical trial comparing fresh (≤ 5 days storage) versus standard issue single-unit RBC transfusion in 100 adult patients receiving invasive mechanically ventilation. Median storage age was 4.0 days (IQR 3.0 - 5.0) versus 26.5 days (IQR 21.0 - 40.0). No differences were noted in the primary outcome of ∆ PaO2/FiO2 (difference between the mean ∆ PaO2/FiO2 in the standard issue RBC group vs. the fresh RBC group = -11.5; 95% CI = -35.3 to 12.3; p = 0.22) or secondary outcomes of markers of immunologic or coagulation status.

Abstract: Kor. Fresh Red Blood Cell Transfusion and Short-term Pulmonary, Immunologic, and Coagulation Status: a Randomized Clinical Trial. Am J Respir Crit Care Med 2012; published January 26


American Journal of Respiratory and Critical Care Medicine:     ICU Readmission

In a retrospective cohort study utilizing 196,202 patients in 156 medical and surgical ICUs in 106 community and academic hospitals, Brown examined the pattern of readmissions to American ICU. 3,905 patients (2.0%) were readmitted to the ICU within 48 hours; 7,171 (3.7%) within 120 hours. Medical patients in academic hospitals are more likely to be readmitted than patients in community hospitals without residents.

Abstract: Brown. The Epidemiology of Intensive Care Unit Readmissions in the United States. Am J. Respir Crit Care Med 2012; published 26 January


JAMA:    Nutrition in Acute Lung Injury

Rice et al publish the EDEN study, a randomized, open-label, multicenter trial, comparing full versus trophic (20% target) enteral feeding for 6 days, in 1000 adults within 48 hours of developing acute lung injury requiring mechanical ventilation. The aim of achieving a difference calorific intake was achieved, with about 1300 kcal/d compared with 400 kcal/d (P < .001) being delivered. Initial trophic feeding did not increase the number of ventilator-free days (14.9 [95% CI, 13.9 to 15.8] vs 15.0 [95% CI, 14.1 to 15.9]; difference, −0.1 [95% CI, −1.4 to 1.2]; P = .89) or reduce 60-day mortality (23.2% [95% CI, 19.6% to 26.9%] vs 22.2% [95% CI, 18.5% to 25.8%]; difference, 1.0% [95% CI, −4.1% to 6.3%]; P = .77) compared with full feeding. There were no differences in infectious complications between the groups. Despite receiving more prokinetic agents, the full-feeding group experienced more vomiting, elevated gastric residual volumes, and constipation, and had higher plasma glucose values and average hourly insulin administration.

Abstract: The National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network. Initial Trophic vs Full Enteral Feeding in Patients With Acute Lung Injury: The EDEN Randomized Trial. JAMA Published online February 5, 2012.


American Heart Journal:     Myocardial Infacrtion

Ranchord and colleagues performed a pilot, randomized controlled trial evaluation titrated oxygen therapy (SpO2 93-96%) versus 6 L/min O2 in 136 patient with uncomplicated NSTEMI. There was no difference in mortality or infarct size between the 2 groups, although confidence intervals were wide.

Abstract:  Ranchord. High-concentration versus titrated oxygen therapy in ST-elevation myocardial infarction: A pilot randomized controlled trial. American Heart Journal 2012;163(2):168-175


January 2012

Journal of Enteral and Parenteral Nutrition:     Parenteral Nutrition

Pontes-Arruda report the results of an international, multicenter, prospective, randomized, open-label, controlled trial which investigated the differences in bacteraemias associated with 2 different parenteral nutrition systems. In 406 patients receiving PN via either a multi-chamber delivery system (n=202), or compounded PN (2 groups, n=101 and n=103 ) the incidence of bacteraemias was significantly lower with the multi-chamber delivery system ( 34 vs 46; p = 0.03). Central line-associated bacteraemias were also significantly lower with the multi-chamber delivery system (10.3 vs 13.2; p < 0.0001).

Abstract: Pontes-Arruda. Influence of Parenteral Nutrition Delivery System on the Development of Bloodstream Infections in Critically Ill Patients: An International, Multicenter, Prospective, Open-Label, Controlled Study—EPICOS Study. JPEN J Parenter Enteral Nutr published 23 January 2012.


European Heart Journal:     Contrast-Induced Nephropathy

Klima et al conducted a prospective, randomized trial in 258 consectutive patients with renal insufficiency undergoing contrast procedures. Patients received intravenous volume supplementation with either (A) sodium chloride 0.9% 1 mL/kg/h for at least 12h prior and after the procedure or (B) sodium bicarbonate (166 mEq/L) 3 mL/kg for 1h before and 1 mL/kg/h for 6h after the procedure or (C) sodium bicarbonate (166 mEq/L) 3 mL/kg over 20min before the procedure plus sodium bicarbonate orally (500 mg per 10 kg). GFR was least affected with sodium chloride therapy, with both sodium bicarbonate therapies being similar. The incidence of contrast-induced nephropathy was significantly smaller with sodium chloride, at 3%, but higher with the bicarbonate therapies at 9% and 10%, respectively.

Abstract: Klima. Sodium chloride vs. sodium bicarbonate for the prevention of contrast medium-induced nephropathy: a randomized controlled trial. Eur Heart J 2012 epublished ahead of print


American Journal of Respiratory and Critical Care Medicine:     24 Hour Intensivist Cover

Epublished ahead of print in the American Journal of Respiratory and Critical Care Medicine, Garland and colleagues report a Canadian pilot study suggesting 24 hour Intensivist cover in ICU makes little difference on clinical outcomes for patients or family satisfaction, results in greater conflicts with nurses and less autonomy for resident staff. However, Intensivists suffered less burnout.

Abstract. Garland.24 Hour Intensivist Presence: A Pilot Study of Effects on ICU Patients, Families, Doctors and Nurses. Am J Resp Crit Care Med 2012 Jan 12; epub ahead of print


JAMA:     Potassium levels in Myocardial Infarction

In this week's issue of JAMA Goyal et al describe the results of a retrospective study over 9 years in 38,689 patients with acute myocardial infarction. Those with either a higher or lower potassium level (< 3.5, >4.5 mEq/L) had increased rates of death (10% v 4.8%), while rates of ventricular fibrillation or cardiac arrest were only higher in those with more extreme potassium levels (<3, >5 mEq/L).

Abstract. Goyal. Serum Potassium Levels and Mortality in Acute Myocardial Infarction. JAMA 2012;307(2):157-164



December 2011 

NEJM:     Venous Thromboembolism Proplylaxis

An international double-blind, placebo-controlled, randomized trial in 8307 acutely ill medical patients was performed to assess the effect of subcutaneous enoxaparin (40 mg daily) as compared with placebo — both administered for 10±4 days in patients who were wearing elastic stockings with graduated compression — on the rate of death from any cause.  There was no difference in either the rate of death at 30 days (4.9% versus 4.8%, p=0.83) or major bleeding (0.4% versus 0.3%, p=0.35). (The LIFENOX study)

Abstract. Kakkar. Low-Molecular-Weight Heparin and Mortality in Acutely Ill Medical Patients. N Engl J Med 2011; 365:2463-2472


JAMA:     Appropriateness of Critical Care

As intensivists who perceive the care they provide as inappropriate experience moral distress and are at risk for burnout, a point-prevalence survey of 1953 intensivists and critical care nurses in 82 adult ICUs in 9 European countries and Israel was performed to determine the prevalence of perceived inappropriateness of care. Perceptions of inappropriate care, including futile therapy and poor distribtion of resources were frequently reported and were inversely associated with factors indicating good teamwork. (APPROPRICUS study)

Abstract. Piers. Perceptions of Appropriateness of Care Among European and Israeli Intensive Care Unit Nurses and Physicians. JAMA 2011; 306:2694-2703


JAMA:    Immunosuppression in Critical Illness

In this week's JAMA, Boomer and colleagues, in a pathological case-control study, compared the immune phenotype of spleen and lungs in subjects who either died of active sepsis (n=40) or had their spleens removed after trauma or brain death (n=20) or lungs from transplant donors or lung cancer resection. Cytokine secretion in sepsis patients was generally less than 10% that in controls, independent of age, duration of sepsis, corticosteroid use, and nutritional status, and was consistent with immunosuppression.

Abstract. Boomer. Immunosuppression in Patients Who Die of Sepsis and Multiple Organ Failure. JAMA 2011;306(23):2594-2605


Anesthesia & Analgesia:     Hydroxyethyl Starch Meta-Analysis

Following the Boldt scandel, Gattas and colleagues performed a systematic analysis comparing the effects of 6% Hydroxyethyl Starch 130/0.4 with other colloid or crystalloid solutions on mortality, acute kidney injury/failure, and bleeding in acutely ill or perioperative patients. 36 studies had initially been reported, of which 11 were subsequently retracted, leaving 19 studies (n = 1246) which were conducted in perioperative patients and 6 (n = 362) in critically ill patients. Published studies were of poor quality and reported too few events to reliably estimate the benefits or risks of administering 6% HES 130/0.4. This same conclusion was reached with or without the retracted studies.

Abstract. Gattas. Fluid Resuscitation with 6% Hydroxyethyl Starch (130/0.4) in Acutely Ill Patients: An Updated Systematic Review and Meta-Analysis. Anesth Analg 2012;114:159-169


Critical Care Medicine:     Acute Lung Injury 

A double-blind, placebo-controlled randomized trial in 130 patients with acute lung injury of 3 days duration failed to demonstrate an effect from human recombinant granulocyte-macrophage colony stimulating factor on ventilator-free days, organ failure-free days or 28 day mortality.

Abstract. Paine. A randomized trial of recombinant human granulocyte-macrophage colony stimulating factor for patients with acute lung injury. Crit Care Med 2012;40(1):90-97


NEJM:     Red Cell Transfusion

Although not a critical care study, The FOCUS study, reported in this week's New England Journal of Medicine further informs the field of transfusion triggers. 2016 patients aged 50 years or older and post hip fracture surgery, with either a history of or risk factors for cardiovascular disease, were randomly assigned to a liberal transfusion strategy (a hemoglobin threshold of 10 g/dl) or restrictive transfusion strategy (symptoms of anemia or at physician discretion for a hemoglobin level of <8 g/dl). There was a mean 2 unit transfusion per patient in the liberal group versus 0 in the restrictive group. No differences were noted between groups for the primary outcome (death or inability to walk across a room;  liberal group 35.2% vs restrictive group 34.7%; odds ratio, 1.01; 95% CI, 0.84 to 1.22),  acute coronary syndromes, or other outcomes.

Abstract:  Carson. Liberal or Restrictive Transfusion in High-Risk Patients after Hip Surgery. N Engl J Med 2011;10.1056/NEJMoa1012452


Lancet:     Acute Lung Injury Therapy

Smith and colleagues report the findings of the BALTI-2 study which assesed the impact of intravenous beta-2 agonist therapy on the outcome of acute lung injury. Previously the BALTI study had demonstrated beta-2 agonist therapy decreased EVLW and plateau pressures in ALI. 162 patients were randomly assigned to the salbutamol group and 164 to the placebo group. Recruitment was stopped after the second interim analysis because of safety concerns. Salbutamol increased 28-day mortality (55 [34%] of 161 patients died in the salbutamol group vs 38 (23%) of 163 in the placebo group; risk ratio [RR] 1·47, 95% CI 1·03—2·08). These findings were consistent with the ALTA study, recently completed by the ARDSnet group.

Abstract: Smith. Effect of intravenous β-2 agonist treatment on clinical outcomes in acute respiratory distress syndrome (BALTI-2): a multicentre, randomised controlled trial. Lancet epub ahead of print December 12 2011


Lancet:     Organogenesis

Is this the future of critical care - extracorporeal organ support whilst a replacement organ is grown?

In today's Lancet Jungebluth and colleagues report a proof-of-concept study detailing the replacement of a cancerous trachea and bronchus with a a stem-cell-seeded bioartificial nanocomposite augmented with growth hormone therapy. The bioartificial nanocomposite had patent anastomoses, lined with a vascularised neomucosa, and was partly covered by nearly healthy epithelium.

Abstract: Jungebluth. Tracheobronchial transplantation with a stem-cell-seeded bioartificial nanocomposite: a proof-of-concept study. Lancet 2011;378(9808):1997-2004