Hot Articles

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

2017

Circulation - N-Acetylcysteine & Nitrate Therapy in STEMI


Thorax - Post ICU Rehabilitation

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


JAMA - FAST Scan in Paediatric Trauma


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


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


Critical Care - Supplementary Parenteral Nutrition


JAMA Surgery - Intraoperative Dexmedetomidine & Post-Op Cognitive Dysfunction


Intensive Care Med - AKI Guideline

American Thoracic Society Conference

NEJM - Angiotensin II for Septic Shock


NEJM - Time to Treatment in Sepsis


JAMA - Outcome Prediction ICU



Thorax - BTS Oxygen Use Guideline


Crit Care Medicine - Paediatric & Neonatal Septic Shock Guideline


Neurology - Brain Injury after CPR Guideline


Chest - Positioning for Endotracheal Intubation


Resuscitation - Video versus Direct Laryngoscopy for Paramedic Endotracheal Intubation


European Journal of Anaesthesiology - Severe Perioperative Bleeding Guideline


Annals of Intensive Care - Post Extubation High Flow Nasal Oxygen


Crit Care Medicine - Stress Ulcer Prophylaxis


American Heart Journal - Nitric Oxide in Acute PE


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

Lancet - Tranexamic Acid for Post Partum Haemorrhage


Lancet Haematology - FFP vs Coagulation Factor Concentrates for Traumatic Coagulopathy


JAMA Internal Medicine - Antiviral Therapy for CMV Reactivation


Annals of Thoracic Surgery - Corticosteroids in Neonatal Cardiac Operations


JAMA - Postoperative Troponin Elevation in Noncardiac Surgery


Intensive Care Medicine - Immunoglobulin for Necrotising Soft Tissue Infection


New England Journal of Medicine - Ularitide in Acute Heart Failure


Intensive Care Medicine - NIV Post Extubation in Chronic Respiratory Disorders


Intensive Care Medicine - IV Chloride Restriction in Cardiac Surgery

Critical Care Medicine - Transfusion in Critically Ill Oncology Patients


J Trauma - Damage Control Resuscitation Guideline


J Crit Care - Tracheostomy Guideline


Intensive Care Med - Condolence Letter


JPEN J Parenter Enteral Nutr - Parenteral Nutrition Guideline


Intensive Care Medicine - Early Enteral Nutrition Guideline


Critical Care Medicine - Contrast-Induced Nephropathy


Critical Care - Pseudomonas Vaccine

Society of Critical Care Medicine Annual Congress

JAMA - Video vs Direct Laryngoscopy for Intubation in ICU

N Engl J Med - Therapeutic Hypothermia for Paediatric Cardiac Arrest

N Engl J Med - Paediatric Glycaemic Control

JAMA - Intubation during Cardiac Arrest


Crit Care Med - Surviving Sepsis Campaign Guidelines


Crit Care Med - Family-Centred Care Guidelines


Chest - Liberation from Mechanical Ventilation Guidelines

2016

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 - HFNO vs NIV

JAMA - OXYGEN-ICU

JAMA - EMPIRICUS

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

2015

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

2014

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!

2013

 

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 Cr