text:
Hot Articles
The following articles have been chosen as the most noteworthy publications in critical care since December 2011.
American Thoracic Society Conference
NEJM - Angiotensin II for Septic Shock
- Khanna. Angiotensin II for the Treatment of Vasodilatory Shock (ATHOS-3 Trial). N Engl J Med 2017;epublished May 21st
NEJM - Time to Treatment in Sepsis
- Seymour. Time to Treatment and Mortality during Mandated Emergency Care for Sepsis. N Engl J Med 2017;epublished May 21st
JAMA - Outcome Prediction ICU
- Detsky. Discriminative Accuracy of Physician and Nurse Predictions for Survival and Functional Outcomes 6 Months After an ICU Admission. JAMA 2017;epublished May 21st
Thorax - BTS Oxygen Use Guideline
- O'Driscoll. BTS guideline for oxygen use in adults in healthcare and emergency settings. Thorax 2017; 72:ii1-ii90
Crit Care Medicine - Paediatric & Neonatal Septic Shock Guideline
- American College of Critical Care Medicine Clinical Practice Parameters for Hemodynamic Support of Pediatric and Neonatal Septic Shock. Crit Care Med 2017;45(6):1061-1093
Neurology - Brain Injury after CPR Guideline
- Geocadin. Practice guideline summary: Reducing brain injury following cardiopulmonary resuscitation. Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology 2017;epublished May 10th
Chest - Positioning for Endotracheal Intubation
- Semler. A Multicenter, Randomized Trial of Ramped Position versus Sniffing Position during Endotracheal Intubation of Critically Ill Adults. Chest 2017;epublished May 12th
Resuscitation - Video versus Direct Laryngoscopy for Paramedic Endotracheal Intubation
- Abstract: Ducharme. A pilot, prospective, randomized trial of video versus direct laryngoscopy for paramedic endotracheal intubation. Resuscitation 2017;114:121–126
European Journal of Anaesthesiology - Severe Perioperative Bleeding Guideline
- Kozek-Langenecker. Management of severe perioperative bleeding: guidelines from the European Society of Anaesthesiology: First update 2016. European Journal of Anaesthesiology 2017;34(6):332–395
Annals of Intensive Care - Post Extubation High Flow Nasal Oxygen
- Fernandez. High-flow nasal cannula to prevent postextubation respiratory failure in high-risk non-hypercapnic patients: a randomized multicenter trial. Annals of Intensive Care 2017;7:47
Crit Care Medicine - Stress Ulcer Prophylaxis
- Alhazzani. Withholding Pantoprazole for Stress Ulcer Prophylaxis in Critically Ill Patients: A Pilot Randomized Clinical Trial and Meta-Analysis. Crit Care Med 2017;epublished April 27th
American Heart Journal - Nitric Oxide in Acute PE
- Kline. Randomized trial of inhaled nitric oxide to treat acute pulmonary embolism: The iNOPE trial. Am Heart J 2017;186:100-110
N Eng J Med - Bystander Efforts in Out-of-Hospital Cardiac Arrest
Lancet - Tranexamic Acid for Post Partum Haemorrhage
- WOMAN Trial Collaborators. Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial. Lancet 2017;epublished April 26th
Lancet Haematology - FFP vs Coagulation Factor Concentrates for Traumatic Coagulopathy
- Innerhofer. Reversal of trauma-induced coagulopathy using first-line coagulation factor concentrates or fresh frozen plasma (RETIC): a single-centre, parallel-group, open-label, randomised trial. Lancet Haematology 2017;epublished April 27th
JAMA Internal Medicine - Antiviral Therapy for CMV Reactivation
- Cowley. Safety and Efficacy of Antiviral Therapy for Prevention of Cytomegalovirus Reactivation in Immunocompetent Critically Ill Patients: A Randomized Clinical Trial. JAMA Intern Med 2017;epublished April 24th
Annals of Thoracic Surgery - Corticosteroids in Neonatal Cardiac Operations
- Suominen. Stress-Dose Corticosteroid Versus Placebo in Neonatal Cardiac Operations: A Randomized Controlled Trial. Ann Thorac Surg 2017;epublished April 20th
JAMA - Postoperative Troponin Elevation in Noncardiac Surgery
- VISION Study Investigators. Association of Postoperative High-Sensitivity Troponin Levels With Myocardial Injury and 30-Day Mortality Among Patients Undergoing Noncardiac Surgery. JAMA 2017;317(16):1642-1651
Intensive Care Medicine - Immunoglobulin for Necrotising Soft Tissue Infection
- Madsen. Immunoglobulin G for patients with necrotising soft tissue infection (INSTINCT): a randomised, blinded, placebo-controlled trial. Intensive Care Med 2017;epublished April 18th
New England Journal of Medicine - Ularitide in Acute Heart Failure
- Packer. Effect of Ularitide on Cardiovascular Mortality in Acute Heart Failure (TRUE-AHF). N Engl J Med 2017;epublished April 12th
Intensive Care Medicine - NIV Post Extubation in Chronic Respiratory Disorders
- Vargas. Intermittent noninvasive ventilation after extubation in patients with chronic respiratory disorders: a multicenter randomized controlled trial (VHYPER). Intensive Care Med 2017;epublished April 9th
Intensive Care Medicine - IV Chloride Restriction in Cardiac Surgery
International Symposium on Intensive Care & Emergency Medicine
N Engl J Med - Levosimendan post Cardiac Surgery
- Landoni. Levosimendan for Hemodynamic Support after Cardiac Surgery (CHEETAH Study). N Engl J Med 2017;epublished March 21st
JAMA - Intraoperative Alveolar Recruitment
- Leme. Effect of Intensive vs Moderate Alveolar Recruitment Strategies Added to Lung-Protective Ventilation on Postoperative Pulmonary Complications. A Randomized Clinical Trial. JAMA 2017;epublished March 21st
JAMA - Dexmedetomidine Sedation in Sepsis
- Yu Kawazoe. Effect of Dexmedetomidine on Mortality and Ventilator-Free Days in Patients Requiring Mechanical Ventilation With Sepsis. A Randomized Clinical Trial (DESIRE Trial). JAMA 2017;epublished March 21st
N Engl J Med - Early Goal-Directed Therapy in Sepsis
- The PRISM Investigators. Early, Goal-Directed Therapy for Septic Shock — A Patient-Level Meta-Analysis. N Engl J Med 2017;epublished March 21st
JAMA - Noradrenaline Shortage
- Vail. Association Between US Norepinephrine Shortage and Mortality Among Patients With Septic Shock. JAMA 2017;epublished March 21st
N Engl J Med - Levosimendan for Cardiac Surgery
Critical Care Medicine - Transfusion in Critically Ill Oncology Patients
- Bergamin. Liberal Versus Restrictive Transfusion Strategy in Critically Ill Oncologic Patients: The Transfusion Requirements in Critically Ill Oncologic Patients Randomized Controlled Trial. Crit Care Med 2017;epublished February 24th
J Trauma - Damage Control Resuscitation Guideline
- Cannon. Damage control resuscitation in patients with severe traumatic hemorrhage: A practice management guideline from the Eastern Association for the Surgery of Trauma. J Trauma Acute Care Surg 2017;82(3):605-617
J Crit Care - Tracheostomy Guideline
- Raimondi. Evidence-based guidelines for the use of tracheostomy in critically ill patients. J Crit Care 2017;38:304–318
JPEN J Parenter Enteral Nutr - Parenteral Nutrition Guideline
- Worthington. When Is Parenteral Nutrition Appropriate? JPEN J Parenter Enteral Nutr 2017;epublished February 1st
Intensive Care Medicine - Early Enteral Nutrition Guideline
- Blaser. Early enteral nutrition in critically ill patients: ESICM clinical practice guidelines. Intensive Care Med 2017;epublished February 6th
Critical Care Medicine - Contrast-Induced Nephropathy
- Valette. Sodium Bicarbonate Versus Sodium Chloride for Preventing Contrast-Associated Acute Kidney Injury in Critically Ill Patients: A Randomized Controlled Trial. Crit Care Med 2017;epublished February 7th
Critical Care - Pseudomonas Vaccine
Society of Critical Care Medicine Annual Congress
JAMA - Video vs Direct Laryngoscopy for Intubation in ICU
- Lascarrou. Video Laryngoscopy vs Direct Laryngoscopy on Successful First-Pass Orotracheal Intubation Among ICU PatientsA Randomized Clinical Trial. JAMA 2017;epublished January 24th
N Engl J Med - Therapeutic Hypothermia for Paediatric Cardiac Arrest
- Moler. Therapeutic Hypothermia after In-Hospital Cardiac Arrest in Children (THAPCA-IH Trial). N Engl J Med 2017;epublished January 24th
N Engl J Med - Paediatric Glycaemic Control
- Agus. Tight Glycemic Control in Critically Ill Children (HALF-PINT Study). N Engl J Med 2017;epublished January 24th
JAMA - Intubation during Cardiac Arrest
- Andersen. Association Between Tracheal Intubation During Adult In-Hospital Cardiac Arrest and Survival. JAMA 2017;epublished January 24th
Crit Care Med - Surviving Sepsis Campaign Guidelines
- Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Crit Care Med 2017;epublished January 17th
Crit Care Med - Family-Centred Care Guidelines
- Davidson. Guidelines for Family-Centered Care in the Neonatal, Pediatric, and Adult ICU. Crit Care Med. 2017;45(1):103-128
Chest - Liberation from Mechanical Ventilation Guidelines
- Ouellette. Liberation From Mechanical Ventilation in Critically Ill Adults: An Official American College of Chest Physicians/American Thoracic Society Clinical Practice Guideline: Inspiratory Pressure Augmentation During Spontaneous Breathing Trials, Protocols Minimizing Sedation, and Noninvasive Ventilation Immediately After Extubation. Chest 2017;151(1):166-180
NEJM - Hypothermia for Status Epilepticus
- Legriel. Hypothermia for Neuroprotection in Convulsive Status Epilepticus (HYBERNATUS Study). N Engl J Med 2016;375:2457-2467
Chest - Inhaled Fosfomycin in Gram Negative VAP
Circulation - Exenatide in Out-of-Hospital Cardiac Arrest
- Wiberg. Neuroprotective Effects of the Glucagon-Like Peptide-1 Analog Exenatide After Out-of-Hospital Cardiac Arrest: A Randomized Controlled Trial. Circulation 2016;epublished November 12th
J Am Coll Cardiol - Impella vs IABP in post MI Cardiogenic Shock
- Ouweneel. Impella CP Versus Intra-Aortic Balloon Pump in Acute Myocardial Infarction Complicated by Cardiogenic Shock: The IMPRESS trial. J Am Coll Cardiol 2016;epublished October 27th
Am J Respir Crit Care Med - Neuroprognostication post Cardiac Arrest
NEJM - Age of Transfused Blood
- Heddle. Effect of Short-Term vs. Long-Term Blood Storage on Mortality after Transfusion. N Engl J Med 2016;epublished October 24th
NEJM - Tranexamic Acid for Coronary Artery Surgery
- Myles. Tranexamic Acid in Patients Undergoing Coronary-Artery Surgery (ATACAS). N Engl J Med 2016;epublished October 23rd
Intensive Care Medicine - High Flow Nasal Oxygen post Abdominal Surgery
- Futier. Effect of early postextubation high-flow nasal cannula vs conventional oxygen therapy on hypoxaemia in patients after major abdominal surgery: a French multicentre randomised controlled trial (OPERA). Intensive Care Med 2016;epublished October 22nd
Intensive Care Medicine - Balanced versus Unbalanced Crystalloids
- Semler. Balanced Crystalloids versus Saline in the Intensive Care Unit: The SALT Randomized Trial. Am J Respir Crit Care Med 201;epublished October 17th
Intensive Care Medicine - HFNO vs NIV for Pre-Oxygenation in Hypoxic ICU patients
- Jaber. Apnoeic oxygenation via high-flow nasal cannula oxygen combined with non-invasive ventilation preoxygenation for intubation in hypoxaemic patients in the intensive care unit: the single-centre, blinded, randomised controlled OPTINIV trial. Intensive Care Med 2016;epublished October 11th
Critical Care - Steroids in Early Sepsis-Associated ARDS
- Tongyoo. Hydrocortisone treatment in early sepsis-associated acute respiratory distress syndrome: results of a randomized controlled trial. Critical Care 2016;20:329
Am J Respir Crit Care Med - Helium / Oxygen in Exacerbations of COPD
- Jolliet. A Multicenter Randomized Trial Assessing the Efficacy of Helium/Oxygen in Severe Exacerbations of Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med 2016;epublished October 13th
Intensive Care Medicine - Intravascular Catheter Dressings
- Günther. Complications of intravascular catheters in ICU: definitions, incidence and severity. A randomized controlled trial comparing usual transparent dressings versus new-generation dressings (the ADVANCED study). Intensive Care Med 2016;epublished October 12th
J Crit Care - Intensity of Feeding
- Rugeles. High-protein hypocaloric vs normocaloric enteral nutrition in critically ill patients: A randomized clinical trial. J Crit Care 2016;35:110–114
NEJM - Levosimendan in Sepsis
- Gordon. Levosimendan for the Prevention of Acute Organ Dysfunction in Sepsis. N Engl J Med 2016;epublished October 5th
JAMA - HFNO vs NIV
- Hernández. Effect of Postextubation High-Flow Nasal Cannula vs Noninvasive Ventilation on Reintubation and Postextubation Respiratory Failure in High-Risk PatientsA Randomized Clinical Trial. JAMA 2016;epublished October 5th
- Girardis. Effect of Conservative vs Conventional Oxygen Therapy on Mortality Among Patients in an Intensive Care Unit. The Oxygen-ICU Randomized Clinical Trial. JAMA 2016;epublished October 5th
- Timsit. Empirical Micafungin Treatment and Survival Without Invasive Fungal Infection in Adults With ICU-Acquired Sepsis, Candida Colonization, and Multiple Organ FailureThe EMPIRICUS Randomized Clinical Trial. JAMA 2016;epublished October 5th
JAMA - Intubation during Paediatric Cardiac Arrest
- Andersen. Association Between Tracheal Intubation During Pediatric In-Hospital Cardiac Arrest and Survival. JAMA 2016;epublished October 4th
Therapeutic Hypothermia & Cardiac Arrest
- Chan. Association Between Therapeutic Hypothermia and Survival After In-Hospital Cardiac Arrest. JAMA 2016;316(13):1375-1382
JAMA - Steroids in Sepsis
Intensive Care Medicine - Fluid Resuscitation in Sepsis
Hjortrup. Restricting volumes of resuscitation fluid in adults with septic shock after initial management: the CLASSIC randomised, parallel-group, multicentre feasibility trial. Intensive Care Med 2016;epublished September 30th
Intensive Care Medicine - Nitric Oxide during Cardiopulmonary Bypass
James. Nitric oxide administration during paediatric cardiopulmonary bypass: a randomised controlled trial. Intensive Care Med 2016;epublished September 30th
Intensive Care Medicine - NAVA
Demoule. Neurally adjusted ventilatory assist as an alternative to pressure support ventilation in adults: a French multicentre randomized trial. Intensive Care Med 2016;epublished September 30th
Intensive Care Medicine - IV Iron for Anaemia
Litton. Intravenous iron or placebo for anaemia in intensive care: the IRONMAN multicentre randomized blinded trial. Intensive Care Med 2016;epublished September 30th
Intensive Care Medicine - Recovery Programme
Jensen. A recovery program to improve quality of life, sense of coherence and psychological health in ICU survivors: a multicenter randomized controlled trial, the RAPIT study. Intensive Care Med 2016;epublished September 30th
Lancet - Early, Goal-Directed Mobilisation
- Schaller. Early, goal-directed mobilisation in the surgical intensive care unit: a randomised controlled trial. Lancet 2016;388(10052):1377–1388
Critical Care Medicine - Dopamine vs Adrenaline in Septic Shock
- Ramaswamy. Double-Blind Randomized Clinical Trial Comparing Dopamine and Epinephrine in Pediatric Fluid-Refractory Hypotensive Septic Shock. Pediatr Crit Care Med 2016;epublished September 23rd
Neurosurgery - 4th Brain Trauma Foundation TBI Guideline
- Carney. Guidelines for the Management of Severe Traumatic Brain Injury, Fourth Edition. Neurosurgery 2016;epublished September 22nd (Executive Summary)
- Complete Guideline - Guidelines for the Management of Severe Traumatic Brain Injury 4th Edition
NEJM - High Flow Nasal Oxygen for Preterm Infants
- Roberts. Nasal High-Flow Therapy for Primary Respiratory Support in Preterm Infants (HIPSTER Trial). N Engl J Med 2016;375:1142-1151
Crit Care Med - Stress Ulcer Prophylaxis
- Selvanderan. Pantoprazole or Placebo for Stress Ulcer Prophylaxis (POP-UP): Randomized Double-Blind Exploratory Study. Crit Care Med 2016;44(10):1842-1850
Liver International - Vasopressor Support for Cirrhosis & Septic Shock
- Choudhury. A randomized trial comparing terlipressin and noradrenaline in patients with cirrhosis and septic shock. Liver Int 2016;epublished September 16th
NEJM - Decompressive Craniotomy
- Hutchinson. Trial of Decompressive Craniectomy for Traumatic Intracranial Hypertension (RESCUEicp). N Engl J Med 2016;epublished September 7th
Am J Respir Crit Care Med - Sevoflurane for Sedation ARDS
- Jabaudon. Sevoflurane for Sedation in ARDS: A Randomized Controlled Pilot Study. Am J Respir Crit Care Med 2016;epublished September 9th
Chinese Medical Journal - Evaluation of Coma after Cardiac Arrest
- Neurocritical Care Committee of the Chinese Society of Neurology (NCC/CSN). The Chinese Expert Consensus on Evaluation of Coma after Cardiopulmonary Resuscitation. Chin Med J 2016;129:2123-7
N Engl J Med - Factor Xa Inhibitor Related Bleeding
Circulation - Therapeutic Hypothermia during Out-of-Hospital Cardiac Arrest
- Bernard. Induction of Therapeutic Hypothermia During Out-of-Hospital Cardiac Arrest Using a Rapid Infusion of Cold Saline (The RINSE Trial). Circulation 2016;epublished August 25th
Lancet - Dexmedetomidine for Prevention of Post-Operative Delirium
- Su. Dexmedetomidine for prevention of delirium in elderly patients after non-cardiac surgery: a randomised, double-blind, placebo-controlled trial. Lancet 2016;epublished August 16th
Burns - Burns Care Guideline
JAMA Surgery - Thrombelastography-Based Dosing of Enoxaparin
- Connelly. Thrombelastography-Based Dosing of Enoxaparin for Thromboprophylaxis in Trauma and Surgical Patients: A Randomized Clinical Trial. JAMA Surg 2016;epublished August 3rd
JAMA - VANISH Trial
- Gordon. Effect of Early Vasopressin vs Norepinephrine on Kidney Failure in Patients With Septic Shock. The VANISH Randomized Clinical Trial. JAMA 2016;316(5):509-518
Journal of Korean Medical Science - Compression Rates during CPR
Lancet Respiratory Medicine - Sedation & Analgesia
- Walsh. Staff education, regular sedation and analgesia quality feedback, and a sedation monitoring technology for improving sedation and analgesia quality for critically ill, mechanically ventilated patients: a cluster randomised trial. Lancet Respir Med 2016;epublished July 26th
JAMA Cardiology - Nonshockable Out-of-Hospital Cardiac Arrest
- Argaud. Effect of Cyclosporine in Nonshockable Out-of-Hospital Cardiac Arrest: The CYRUS Randomized Clinical Trial (CYRUS Study). JAMA Cardiol 2016;epublished July 13th
Shock - Hydrocortisone in Septic Shock
- Hervé. Effects of Increasing Hydrocortisone to 300 MG per Day in the Treatment of Septic Shock: A Pilot Study. Shock 2016;epublished July 11th
JAMA Internal Medicine - Sodium Selenite & Procalcitonin in Sepsis
- Bloos. Effect of Sodium Selenite Administration and Procalcitonin-Guided Therapy on Mortality in Patients With Severe Sepsis or Septic Shock. A Randomized Clinical Trial. JAMA Intern Med 2016;epublished July 18th
Journal of Critical Care - Heparin for Pneumonia in Ventilated Patients
- IPHIVAP investigators of the ANZICS CTG. Is inhaled prophylactic heparin useful for prevention and management of pneumonia in ventilated ICU patients? J Crit Care 2016;epublished July 15th
European Heart Journal - Acute Heart Failure Guideline
- Ponikowski. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Eur Heart J 2016;37:2129-2200
Clinical Infectious Diseases - HAP & VAP Guideline
- Kalil. Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis 2016;epublished July 14th
Am J Respir & Crit Care Med - Burnout Syndrome in Critical Care Professionals
- Moss. A Critical Care Societies Collaborative Statement: Burnout Syndrome in Critical Care Health-care Professionals. A Call for Action. Am J Respir Crit Care Med 2016;194(1):106-113
JAMA - Palliative Care-Led Meetings
Intensive Care Medicine - Protein C Zymogen in Sepsis
- Pappalardo. Protein C zymogen in severe sepsis: a double-blinded, placebo-controlled, randomized study. Intensive Care Med 2016;epublished June 25th
Lancet - PanScan in Trauma
- Sierink. Immediate total-body CT scanning versus conventional imaging and selective CT scanning in patients with severe trauma (REACT-2): a randomised controlled trial. Lancet 2016;epublished June 28th
NEJM - Haemorrhage Stroke
- Qureshi. Intensive Blood-Pressure Lowering in Patients with Acute Cerebral Hemorrhage (ATCH-2). N Eng J Med 2016;epublished June 8th
JAMA - Rehabilitation in Acute Respiratory Failure
- Morris. Standardized Rehabilitation and Hospital Length of Stay Among Patients With Acute Respiratory Failure. A Randomized Clinical Trial. JAMA 2016;315(24):2694-2702
Journal of the American College of Cardiology - Erythropoietin in Out-of-Hospital Cardiac Arrest
- Cariou. Early High-Dose Erythropoietin Therapy After Out-of-Hospital Cardiac Arrest: A Multicenter, Randomized Controlled Trial. J Am Coll Cardiol 2016;68(1):40
JAMA - Mental Health Post Sepsis
Lancet - Platelet Transfusion in Haemorrhagic Stroke
- Baharoglu. Platelet transfusion versus standard care after acute stroke due to spontaneous cerebral haemorrhage associated with antiplatelet therapy (PATCH): a randomised, open-label, phase 3 trial (PATCH Trial). Lancet 2016;epublished May 10th
JAMA - Timing of Renal Replacement Therapy in AKI
- Zarbock. Effect of Early vs Delayed Initiation of Renal Replacement Therapy on Mortality in Critically Ill Patients With Acute Kidney Injury. The ELAIN Randomized Clinical Trial. JAMA 2016;epublished May 22nd
American Thoracic Society Meeting
New England Journal of Medicine: Timing of Renal Replacement Therapy in AKI
- Gaudry. Initiation Strategies for Renal-Replacement Therapy in the Intensive Care Unit (AKIKI Study). N Engl J Med 2016;epublished May 15th
JAMA: Aspirin for the Prevention of ARDS
- Kor. Effect of Aspirin on Development of ARDS in At-Risk Patients Presenting to the Emergency DepartmentThe LIPS-A Randomized Clinical Trial (LIPS-A Trial). JAMA 2016;epublished May 15th
JAMA: Helmet NIV for ARDS
- Patel. Effect of Noninvasive Ventilation Delivered by Helmet vs Face Mask on the Rate of Endotracheal Intubation in Patients With Acute Respiratory Distress Syndrome. A Randomized Clinical Trial. JAMA 2016;epublished May 15th
American Journal of Kidney Disease: Renal Replacement Therapy Dose
- Park. High-Dose Versus Conventional-Dose Continuous Venovenous Hemodiafiltration and Patient and Kidney Survival and Cytokine Removal in Sepsis-Associated Acute Kidney Injury: A Randomized Controlled Trial (HICORES Trial). Am J Kidney Dis 2016;epublished April 12th
Journal of the American College of Cardiology: Early Aldosterone Blockade in Acute MI
- Beygui. Early Aldosterone Blockade in Acute Myocardial Infarction. The ALBATROSS Randomized Clinical Trial. J Am Coll Cardiol 2016;67(16):1917-1927
Resuscitation: Video Laryngoscopy during CPR
- Kim. Video laryngoscopy vs. direct laryngoscopy: which should be chosen for endotracheal intubation during cardiopulmonary resuscitation?: A prospective randomized controlled study of experienced intubators. Resuscitation 2016;epublished April 16th
Critical Care: European Guideline on Bleeding & Coagulopathy post Trauma
- Rossaint. The European guideline on management of major bleeding and coagulopathy following trauma: fourth edition. Critical Care 2016;20:100
JAMA: Checklists
- BRICNet. Effect of a Quality Improvement Intervention With Daily Round Checklists, Goal Setting, and Clinician Prompting on Mortality of Critically Ill Patients. A Randomized Clinical Trial (CHECKLIST-ICU). JAMA 2016;315(14):1480-1490
Resuscitation: Hypercapnoea post Cardiac Arrest
- Eastwood. Targeted therapeutic mild hypercapnia after cardiac arrest: A phase II multi-centre randomised controlled trial (the CCC trial). Resuscitation 2016;epublished April 7th
NEJM: Antiarrhythmics in Out-of-Hospital Cardiac Arrest
- Kudenchuk. Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest. N Engl J Med 2016;epublished April 4th
Critical Care: Steroids for Refractory Shock post Cardiac Arrest
- Donnino. Corticosteroid therapy in refractory shock following cardiac arrest: a randomized, double-blind, placebo-controlled, trial. Critical Care 2016;20:82
Intensive Care Medicine: Probiotics for the Prevention of VAP
Brussel's International Symposium on Intensive Care & Emergency Medicine
JAMA: Dexmedetomidine Sedation in ICU
- Full Text: Reade. Effect of Dexmedetomidine Added to Standard Care on Ventilator-Free Time in Patients With Agitated DeliriumA Randomized Clinical Trial (DahLIA Trial). JAMA 2016;epublished March 15th
JAMA: High-Flow Nasal Oxygen post Extubation
- Full Text: Hernández. Effect of Postextubation High-Flow Nasal Cannula vs Conventional Oxygen Therapy on Reintubation in Low-Risk PatientsA Randomized Clinical Trial. JAMA 2016;epublished March 15th
JAMA: Non-Invasive Ventilation post Extubation after Abdominal Surgery
- Full Text: Jaber. Effect of Noninvasive Ventilation on Tracheal Reintubation Among Patients With Hypoxemic Respiratory Failure Following Abdominal Surgery: A Randomized Clinical Trial (NIVAS). JAMA 2016;epublished March 15th
JAMA: Secondary Infections post Sepsis
- Full Text: van Vught. Incidence, Risk Factors, and Attributable Mortality of Secondary Infections in the Intensive Care Unit After Admission for Sepsis. JAMA 2016;epublished March 15th
NEJM: Early TPN in Childern
- Full Text: Fivez. Early versus Late Parenteral Nutrition in Critically Ill Children (PEPaNIC Trial). N Engl J Med 2016;epublished March 15th
Critical Care Medicine: Fragility Index in Critical Care
- Ridgeon. The Fragility Index in Multicenter Randomized Controlled Critical Care Trials. Critical Care Med 2016;epublished March 9th
Journal of Infection - UK Meningitis Guidelines
- McGill. The UK joint specialist societies guideline on the diagnosis and management of acute meningitis and meningococcal sepsis in immunocompetent adults. Journal of Infection 2016;72:405-438
JAMA - Sepsis Definition
- Singer. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016;315(8):801-810
- Seymor. Assessment of Clinical Criteria for Sepsis: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016;315(8):762-774
- Shankar-Hari. Developing a New Definition and Assessing New Clinical Criteria for Septic Shock: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 2016;315(8):775-787
JAMA - Statins for AKI
- Billings. High-Dose Perioperative Atorvastatin and Acute Kidney Injury Following Cardiac Surgery. A Randomized Clinical Trial. JAMA 2016;epublished February 23rd
JAMA - ARDS Epidemiology
Lancet Respiratory Medicine - Effect of Light on Delirium
- Abstract: Simons. Dynamic light application therapy to reduce the incidence and duration of delirium in intensive-care patients: a randomised controlled trial. Lancet Respir Med 2016;epublished February 16th
Intensive Care Medicine - Blood Pressure Targets in Shock
- Abstract: Lamontagne. Higher versus lower blood pressure targets for vasopressor therapy in shock: a multicentre pilot randomized controlled trial. (OVATION). Intensive Care Med 2016;epublished February 18th
NICE Trauma Guideline
- NICE. Major trauma: assessment and initial management. NICE 2016;epublished February
- NICE. Major trauma: service delivery. NICE 2016;epublished February
JAMA - Acetazolamide for COPD
- Abstract: Faisy. Effect of Acetazolamide vs Placebo on Duration of Invasive Mechanical Ventilation Among Patients With Chronic Obstructive Pulmonary Disease: A Randomized Clinical Trial. JAMA 2016;315(5):480
Intensive Care Medicine - Percutaneous Dilational Tracheostomy
- Abstract: Gobatto. Ultrasound-guided percutaneous dilational tracheostomy versus bronchoscopy-guided percutaneous dilational tracheostomy in critically ill patients (TRACHUS): a randomized noninferiority controlled trial. Intensive Care Med 2016;epublished February 1st
Pediatric Crit Care Med - Aminophylline for Prevention of AKI
Blue Journal - End-of-Life Communication
- Abstract: Curtis. Randomized Trial of Communication Facilitators to Reduce Family Distress and Intensity of End-of-Life Care. Am J Respir Crit Care Med 2016;193(2):154-162
JPEN J Parenter Enteral Nutr - Nutritional Support in the Critically Ill
- Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) JPEN J Parenter Enteral Nutr 2016;40(2):159-211
Intensive Care Medicine - Continuous vs Intermittent Beta Lactam Infusion
- Abstract: Abdul-Aziz. Beta-Lactam Infusion in Severe Sepsis (BLISS): a prospective, two-centre, open-labelled randomised controlled trial of continuous versus intermittent beta-lactam infusion in critically ill patients with severe sepsis. Intensive Care Med 2016;epublished January 11th
Chest - Antithrombotic Therapy for VTE
- Antithrombotic Therapy for VTE Disease : CHEST Guideline and Expert Panel Report. Chest 2016;epublished January 7th
Resuscitation - TTM post Cardiac Arrest
- Canadian Guidelines for the use of targeted temperature management (therapeutic hypothermia) after cardiac arrest: A joint statement from The Canadian Critical Care Society (CCCS), Canadian Neurocritical Care Society (CNCCS), and the Canadian Critical Care Trials Group (CCCTG). Resuscitation 2016;98:48-63
German Medical Society - Delirium, Analgesia & Sedation Guideline
- Evidence and consensus based guideline for the management of delirium, analgesia, and sedation in intensive care medicine. Revision 2015 (DAS-Guideline 2015) - short version. Ger Med Sci 2015;12;13
Annals of Intensive Care - Renal Replacement Therapy Guideline
- Vinsonneau. Renal replacement therapy in adult and pediatric intensive care : Recommendations by an expert panel from the French Intensive Care Society (SRLF) with the French Society of Anesthesia Intensive Care (SFAR) French Group for Pediatric Intensive Care Emergencies (GFRUP) the French Dialysis Society (SFD). Ann Intensive Care 2015;5(1):58
ANZICS - Acute Pain Management Scientific Evidence
Journal of Thrombosis and Haemostasis - Guideline on Antidotes for Direct Oral Anticoagulants
- Levy. When and how to use antidotes for the reversal of direct oral anticoagulants: guidance from the SSC of the ISTH. Journal of Thrombosis and Haemostasis 2015;2015;epublished December 15th
American Journal of Respiratory & Critical Care Medicine: Physical Therapy for Respiratory Failure
- Moss. A Randomized Trial of an Intensive Physical Therapy Program for Acute Respiratory Failure Patients. Am J Respir Crit Care Med 2015;epublished December 10th
NICE Guideline on Acute Heart Failure
NICE Guideline on IV Fluid Therapy in Young People
- NICE. Intravenous fluid therapy in children and young people in hospital. NICE 2015;epublished December 9th
Journal of Trauma: Western Trauma Guidelines
- Feliciano. Western Trauma Association Critical Decisions in Trauma: Management of abdominal vascular. J Trauma Acute Care Surg 2015;79(6):1079-1088
- Biffl. Western Trauma Association Critical Decisions in Trauma: Diagnosis and management of esophageal injuries. J Trauma Acute Care Surg 2015;79(6):1089–1095
- Malhotra. Western Trauma Association Critical Decisions in Trauma: Diagnosis and management of duodenal injuries. J Trauma Acute Care Surg 2015;79(6):1096–1101
Critical Care Medicine: SCCM Guideline on Ultrasound in Critical Care
- Frankel. Guidelines for the Appropriate Use of Bedside General and Cardiac Ultrasonography in the Evaluation of Critically Ill Patients—Part I: General Ultrasonography. Crit Care Med 2015;43(11):2479-2502
Critical Care Medicine: SCCM Guideline on Organ Procurement
- Kotloff. Management of the Potential Organ Donor in the ICU: Society of Critical Care Medicine/American College of Chest Physicians/Association of Organ Procurement Organizations Consensus Statement. Crit Care Med 2015;43(6):1291-325
Critical Care Medicine: SCCM Guideline on ICU Process & Structures
- Weled. Critical Care Delivery: The Importance of Process and ICU Structure to Improved Outcomes. Crit Care Med 2015 Jul;43(7):1520-5
Lancet Infectious Diseases: Body Surface Decolonization & UTIs
- Huang. Effect of body surface decolonisation on bacteriuria and candiduria in intensive care units: an analysis of a cluster-randomised trial. Lancet Infect Dis 2015;epublished November 26th
JAMA: Transfusion in Anaemic Children with Elevated Lactate
Lancet Respiratory Medicine: Refeeding Syndrome
- Doig. Restricted versus continued standard caloric intake during the management of refeeding syndrome in critically ill adults: a randomised, parallel-group, multicentre, single-blind controlled trial. Lancet Respir Med 2015;epublished November 16th
Respiratory Care: High Flow Nasal Oxygen
- Jones. Randomized Controlled Trial of Humidified High-Flow Nasal Oxygen for Acute Respiratory Distress in the Emergency Department: The HOT-ER Study. Respir Care 2015;epublished November 17th
New England Journal of Medicine: Continuous vs Interrupted CPR
- Nichol. Trial of Continuous or Interrupted Chest Compressions during CPR. New Eng J Med 2015;epublished November 9th
Difficult Airway Society Guideline
- Frerk. Difficult Airway Society 2015 guidelines for management of unanticipated difficult intubation in adults. Br J Anaesth 2015;epublished November 10th
World Allergy Organisation Anaphylaxis Guideline
Intensive Care Medicine: Post-Resuscitation Care Guideline
- Nolan. European Resuscitation Council and European Society of Intensive Care Medicine 2015 guidelines for post-resuscitation care. Resuscitation 2015;95:202-222
American Heart Association: ST-Elevation MI Guideline Update
- 2015 ACC/AHA/SCAI Focused Update on Primary Percutaneous Coronary Intervention for Patients With ST-Elevation Myocardial Infarction: An Update of the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention and the 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction. Circulation 2015;epublished October 21st
American Heart Association: Infective Endocarditis Guideline
- Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications. A Scientific Statement for Healthcare Professionals From the American Heart Association. Circulation 2015;132:00-00
2015 Cardiac Arrest Guidelines
- Part 1: Executive Summary: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015;132:S315-S367
- 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
- Part 3: Ethical Issues: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015;132:S383-S396
- 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
- 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
- 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
- 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
- Part 8: Post–Cardiac Arrest Care: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015;132:S465-S482
- Part 9: Acute Coronary Syndromes: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015;132:S483-S500
- Part 10: Special Circumstances of Resuscitation: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015;132:S501-S518
- 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
- Part 12: Pediatric Advanced Life Support: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care
- Circulation 2015;132:S526-S542
- Part 13: Neonatal Resuscitation: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015;132:S543-S560
- 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
- Young. Effect of a Buffered Crystalloid Solution vs Saline on Acute Kidney Injury Among Patients in the Intensive Care Unit (SPLIT Trial). JAMA 2015;epublished October 7th
JAMA: Paracetamol for Fever in Critically ill with Suspected Infection
- Young. Acetaminophen for Fever in Critically Ill Patients with Suspected Infection (HEAT Trial). N Eng J Med 2015;epublished October 5th
Lancet: Erythropoietin for Traumatic Brain Injury
- Nichol. Erythropoietin in traumatic brain injury (EPO-TBI): a double-blind randomised controlled trial. Lancet 2015;epublished October 7th
N Engl J Med: Hypothermia for Intracranial Hypertension in Traumatic Brain Injury
- Andrews. Hypothermia for Intracranial Hypertension after Traumatic Brain Injury (Eurotherm3235 Trial). N Engl J Med 2015;epublished October 7th
Am J Respir Crit Care Med: Apnoeic Oxygenation
JAMA: ICU Admission for Older Adults with Pneumonia
- Valley. Association of Intensive Care Unit Admission With Mortality Among Older Patients With Pneumonia. JAMA 2015;314(12):1272-1279
JAMA: Do-Not-Resuscitate Status
- Fendler. Alignment of Do-Not-Resuscitate Status With Patients' Likelihood of Favorable Neurological Survival After In-Hospital Cardiac Arrest. JAMA 2015;314(12):1264-1271
NEJM: CVC Insertion Site
- Parienti. Intravascular Complications of Central Venous Catheterization by Insertion Site (3SITES Study). N Engl J Med 2015;373:1220-1229
Clinical Drug Investigation: Esmolol for Sepsis
- Wang. Combination Therapy with Milrinone and Esmolol for Heart Protection in Patients with Severe Sepsis: A Prospective, Randomized Trial. Clinical Drug Investigation 2015;epublished September 19th
Lancet: Methylprednisolone for Cardiopulmonary Bypass
- Whitlock. Methylprednisolone in patients undergoing cardiopulmonary bypass (SIRS): a randomised, double-blind, placebo-controlled trial. Lancet 2015;386(10,000):1243–1253
Lancet: Sigmoid Diverticulitis
- Vennix. Laparoscopic peritoneal lavage or sigmoidectomy for perforated diverticulitis with purulent peritonitis: a multicentre, parallel-group, randomised, open-label trial (Ladies trial). Lancet 2015;386(10000):1269–1277
Lancet: CVC Line Infection Prevention
- Mimoz. Skin antisepsis with chlorhexidine–alcohol versus povidone iodine–alcohol, with and without skin scrubbing, for prevention of intravascular-catheter-related infection (CLEAN): an open-label, multicentre, randomised, controlled, two-by-two factorial trial (CLEAN trial). Lancet 2015;epublished September 17th
American Journal of Respiratory & Crit Care Med: End-of-Life Care
- Curtis. Randomized Trial of Communication Facilitators to Reduce Family Distress and Intensity of End-of-life Care. Am J Respir Crit Care Med 2015;epublished September 17th
Critical Care: Laxative Therapy
- de Azevedo. Daily laxative therapy reduces organ dysfunction in mechanically ventilated patients: a phase II randomized controlled trial. Critical Care 2015;19:329
Lancet: Oxyenation Target in Bronchiolitis
- Cunningham. Oxygen saturation targets in infants with bronchiolitis (BIDS): a double-blind, randomised, equivalence trial. Lancet 2015;386(9998):1041–1048
Lancet: Bubble CPAP for Paediatric Pneumonia
- Chisti. Bubble continuous positive airway pressure for children with severe pneumonia and hypoxaemia in Bangladesh: an open, randomised controlled trial. Lancet 2015;386(9998):1057-1065
European Journal of Anesthesiology: Pre-Oxygenation
- Hanouz. Preoxygenation by spontaneous breathing or noninvasive positive pressure ventilation with and without positive end-expiratory pressure: A randomised controlled trial. Eur J Anaesthesiol 2015;epublished July 29th
Critical Care Medicine: Vasopressors for Paediatric Septic Shock
- Ventura. Double-Blind Prospective Randomized Controlled Trial of Dopamine Versus Epinephrine as First-Line Vasoactive Drugs in Pediatric Septic Shock. Crit Care Med 2015;epublished August 28th
Blue Journal: Oxygenation Targets in Mechanically Ventilated Patients
- Panwar. Conservative Versus Liberal Oxygenation Targets for Mechanically Ventilated Patients - a Pilot Multicenter Randomized Controlled Trial (CLOSE Study). Am J Respir Crit Care Med 2015;epublished September 3rd
Journal of Hepatology: Plasma Exchange for Acute Liver Failure
- Larsen. High-volume plasma exchange in patients with acute liver failure: An open randomised controgenation lled trial. J Hepatol 2015;epublished August 29th
Circulation: ESC Guidelines on Pulmonary Hypertension | Pericardial Disease | Non-Persistent ST Elevation Coronary Syndromes | Infective Endocarditis
- Galiè. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Circulation 2015;epublished August 29th
- Adler. 2015 ESC Guidelines for the diagnosis and management of pericardial diseases. Circulation 2015;epublished August 29th
- Roffi. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Circulation 2015;epublished August 29th
- Habib. 2015 ESC Guidelines for the management of infective endocarditis. Circulation 2015;epublished August 29th
British Journal of Haematology: Guideline on Admission for Haematology Cancer Patients
- Wise. Guidelines on the management and admission to intensive care of critically ill adult patients with haematological malignancy in the UK. British Journal of Haematology 2015;epublished August 19th
Journal of Trauma: Early Surgery in Traumatic Brain Injury
- Mendelow. Early Surgery versus Initial Conservative Treatment in Patients with Traumatic Intracerebral Hemorrhage (STITCH (Trauma)): The First Randomized Trial. Journal of Neurotrauma 2015;32(17):1312-1323
Annals of Surgery: Cryopreserved Packed Red Cells
- Schreiber. Transfusion of Cryopreserved Packed Red Blood Cells Is Safe and Effective After Trauma: A Prospective Randomized. Trial. Annals of Surgery 2015;262(3):426–433
NEJM / Lancet: Idarucizumab for Dabigatran
- Pollack. Idarucizumab for Dabigatran Reversal. N Engl J Med 2015;373(6):511-20
- Glund. Safety, tolerability, and efficacy of idarucizumab for the reversal of the anticoagulant effect of dabigatran in healthy male volunteers: a randomised, placebo-controlled, double-blind phase 1 trial. Lancet 2015;386(9994):680–690
Lancet: Bioprosthetic Total Artificial Heart Heart
- Carpentier. First clinical use of a bioprosthetic total artificial heart: report of two cases. Lancet 2015;epublished July 28th
New England Journal of Medicine: Hypothermia for Deceased Kidney Donor Graft
JAMA: Bystander CPR
- Nakahara. Association of Bystander Interventions With Neurologically Intact Survival Among Patients With Bystander-Witnessed Out-of-Hospital Cardiac Arrest in Japan. JAMA 2015;314(3):247-254
Blue Journal: β-Lactam Infusion in Severe Sepsis
- Dulhunty. A Multicenter Randomized Trial of Continuous versus Intermittent β-Lactam Infusion in Severe Sepsis. Am J Respir Crit Care Med 2015;epublished July 22nd
Perioperative Medicine: Stroke Volume Variation
- Jammer. Stroke volume variation to guide fluid therapy: is it suitable for high-risk surgical patients? A terminated randomized controlled trial. Perioperative Medicine 2015;4:6
Critical Care Medicine: Critical Care Interventions
- Landoni. Mortality in Multicenter Critical Care Trials: An Analysis of Interventions With a Significant Effect. Crit Care Med 2015;43(8):1559–1568
Blue Journal: Haemofiltration for Postcardiac Surgery Shock
- Combes. Early High-volume Hemofiltration vs. Standard Care for Postcardiac Surgery Shock (The HEROICS Study). Am J Respir Crit Care Med 2015;epublished July 13th
Annals of Surgery: Abdominal Vacuum Therapy post Laparotomy
- Kirkpatrick. Active Negative Pressure Peritoneal Therapy After Abbreviated Laparotomy: The Intraperitoneal Vacuum Randomized Controlled Trial. Ann Surg 2015;262(1):38–46
Annals of Intensive Care: Guideline on Cardiogenic Shock
Journal of Trauma: Guideline on ED Thoracotomy
- Seamon. An evidence-based approach to patient selection for emergency department thoracotomy: A practice management guideline from the Eastern Association for the Surgery of Trauma. J Trauma 2015;79(1):159–173
Critical Care Medicine: Hypothermia for Paediatric Traumatic Brain Injury
- Beca. Hypothermia for Traumatic Brain Injury in Children—A Phase II Randomized Controlled Trial. Crit Care Med 2015;43(7):1458–1466
Circulation: Targeted Temperature Management
- Deye. Endovascular versus External Targeted Temperature Management for Out-of-Hospital Cardiac Arrest Patients: A Randomized Controlled Study. (ICEREA Study). Circulation 2015;epublished June 19th
New England Journal of Medicine: Out-of-Hospital CPR
- Hasselqvist-Ax. Early Cardiopulmonary Resuscitation in Out-of-Hospital Cardiac Arrest. N Engl J Med 2015;372:2307-2315
- Ringh. Mobile-Phone Dispatch of Laypersons for CPR in Out-of-Hospital Cardiac Arrest. N Engl J Med 2015;372:2316-2325
New England Journal of Medicine: Stroke Thrombolysis
- Saver. Stent-Retriever Thrombectomy after Intravenous t-PA vs. t-PA Alone in Stroke (SWIFT PRIME study). N Engl J Med 2015;372:2285-2295
New England Journal of Medicine: Stroke Thrombectomy
- Jovin. Thrombectomy within 8 Hours after Symptom Onset in Ischemic Stroke. (REVASCAT Trial). N Engl J Med 2015;372:2296-2306
Blue Journal: Guideline on Requests for Inappropriate ICU Therapy
- Bosslet. An Official ATS/AACN/ACCP/ESICM/SCCM Policy Statement: Responding to Requests for Potentially Inappropriate Treatments in Intensive Care Units. Am J Respir Crit Care Med 2015;191(11):1318-1330
Blue Journal: Guideline on Managing Conscientious Objections in ICM
- Lewis-Newby. An Official American Thoracic Society Policy Statement: Managing Conscientious Objections in Intensive Care Medicine. Am J Respir Crit Care Med 2015;191(2):219-227
Journal of Cardiac Failure: Statement on Percutaneous Mechanical Circulatory Support
- Rihal. 2015 SCAI/ACC/HFSA/STS Clinical Expert Consensus Statement on the Use of Percutaneous Mechanical Circulatory Support Devices in Cardiovascular Care (Endorsed by the American Heart Association, the Cardiological Society of India, and Sociedad Latino Americana de Cardiologia Intervencion; Affirmation of Value by the Canadian Association of Interventional Cardiology-Association Canadienne de Cardiologie d'intervention). J Card Fail 2015;21(6):499-518
European Heart Journal: Guideline on Acute Heart Failure
- Mebazaa. Recommendations on pre-hospital and early hospital management of acute heart failure: a consensus paper from the Heart Failure Association of the European Society of Cardiology, the European Society of Emergency Medicine and the Society of Academic Emergency Medicine – short version. European Heart Journal 2015;epublished May 21st
Stroke: Guideline on Spontaneous Intracerebral Haemorrhage
- Hemphill. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2015;epublished May 28th
Critical Care Medicine: Talactoferrin for Sepsis
- Vincent. Talactoferrin in Severe Sepsis: Results From the Phase II/III Oral tAlactoferrin in Severe sepsIS Trial. Crit Care Med 2015;epublished May 22nd
New England Journal of Medicine: Intra-Abdominal Infection
- Sawyer. Trial of Short-Course Antimicrobial Therapy for Intraabdominal Infection (STOP-IT trial). N Engl J Med 2015; 372:1996-2005
American Thoracic Society Meeting 2015
New England Journal of Medicine: Underfeeding
- Arabi. Permissive Underfeeding or Standard Enteral Feeding in Critically Ill Adults (PermiT Trial). N Engl J Med 2015;epublished May 20th
New England Journal of Medicine: High Flow Nasal Oxygen
- Frat. High-Flow Oxygen through Nasal Cannula in Acute Hypoxemic Respiratory Failure (FLORALI study). N Eng J Med 2015;epublished May 17th
Journal of the American Medical Association: High Flow Nasal Oxygen
- Stéphan. High-Flow Nasal Oxygen vs Noninvasive Positive Airway Pressure in Hypoxemic Patients After Cardiothoracic Surgery: A Randomized Clinical Trial. JAMA 2015;epublished May 17th
Lancet: Red Cell Transfusion in Upper GI Haemorrhage
- Jairath. Restrictive versus liberal blood transfusion for acute upper gastrointestinal bleeding (TRIGGER): a pragmatic, open-label, cluster randomised feasibility trial. Lancet 2015;epublished May 5th
British Medical Journal: MRSA Therapy
- Paul. Trimethoprim-sulfamethoxazole versus vancomycin for severe infections caused by meticillin resistant Staphylococcus aureus: randomised controlled trial. BMJ 2015;350:h2219
AJRCCM: GUIDELINE - Conscientious Objections in ICU
Intensive Care Society: Provision of Intensive Care Servces
- Intensive Care Society. Guidelines for the Provision of Intensive Care Services 2015;epublished April 21st
Neurocritical Care: Hemispheric Infarction
- Torbey. Evidence-Based Guidelines for the Management of Large Hemispheric Infarction. A Statement for Health Care Professionals from the Neurocritical Care Society and the German Society for Neuro-Intensive Care and Emergency Medicine. Neurocrit Care 2015;22:146–16
Neurocritical Care: Devastating Brain Injury
- Souter. Recommendations for the Critical Care Management of Devastating Brain Injury: Prognostication, Psychosocial, and Ethical Management. A Position Statement for Healthcare Professionals from the Neurocritical Care Society. Neurocrit Care 2015;epublished April 18th
Swiss Medical Weekly: Ethics in ICU
- Swiss Academy of Medical Sciences. Medical ethical guidelines: Intensive-care interventions. Swiss Med Wkly 2015;145:w14109
New England Journal of Medicine: Paediatric Therapeutic Hypothermia post Cardiac Arrest
- Moler. Therapeutic Hypothermia after Out-of-Hospital Cardiac Arrest in Children (THAPCA Trial). N Engl J Med 2015;epublished April 25th
New England Journal of Medicine: Alcoholic Hepatitis
- Thursz. Prednisolone or Pentoxifylline for Alcoholic Hepatitis (STOPAH Trial). N Engl J Med 2015;372:1619-1628
Intensive Care Medicine: High Flow Nasal Cannulae Oxygen for Intubation
- Vourc'h. High-flow nasal cannula oxygen during endotracheal intubation in hypoxemic patients: a randomized controlled clinical trial. Intensive Care Med 2015;epublished April 14th
JAMA Internal Medicine: Post ICU Rehabilitation
- Walsh. Increased Hospital-Based Physical Rehabilitation and Information Provision After Intensive Care Unit DischargeThe RECOVER Randomized Clinical Trial. JAMA Intern Med 2015;epublished April 13th
Intensive Care Medicine: Polymyxin B Hemoperfusion
- Payen. Early use of polymyxin B hemoperfusion in patients with septic shock due to peritonitis: a multicenter randomized control trial (ABDOMIX study). Intensive Care Med 2015;epublished April 11th
Chest: Surfactant in ARDS
- Willson. The Adult Calfactant in Acute Respiratory Distress Syndrome (CARDS) Trial. Chest 2015;epublished April 9th
Intensive Care Medicine: Early Rehabilitation
- Kayambu. Early physical rehabilitation in intensive care patients with sepsis syndromes: a pilot randomised controlled trial. Intensive Care Med 2015;epublished April 8th
Critical Care Medicine: Regional Citrate Anticoagulation for RRT
- Gatas. A Randomized Controlled Trial of Regional Citrate Versus Regional Heparin Anticoagulation for Continuous Renal Replacement Therapy in Critically Ill Adults. Crit Care Med 2015;epublished April 6th
NEJM: Age of Transfused Red Cells
International Symposium on Intensive Care and Emergency Medicine Update
NEJM: Early Goal-Directed Sepsis Therapy
- Mouncey. Trial of Early, Goal-Directed Resuscitation for Septic Shock. (ProMISe Trial). N Engl J Med 2015;epublished March 17th
NEJM: Age of Transfused Red Cells
- Lacroix. Age of Transfused Blood in Critically Ill Adults (ABLE Study). N Engl J Med 2015;epublished March 17th
NEJM: ANZICS SIRS Criteria in Sepsis
- Kaukonen. Systemic Inflammatory Response Syndrome Criteria in Defining Severe Sepsis. N Engl J Med 2015;epublished March 17th
NEJM: Transfusion Thresholds in Cardiac Surgery
NEJM: ARDS Driving Pressure
- Amato. Driving Pressure and Survival in the Acute Respiratory Distress Syndrome. N Engl J Med 2015; 372:747-755
JAMA: Steroids for Community-Acquired Pneumonia
- Abstract: Torres. Effect of Corticosteroids on Treatment Failure Among Hospitalized Patients With Severe Community-Acquired Pneumonia and High Inflammatory Response. A Randomized Clinical Trial. JAMA 2015;313(7):677-686
Acta Anaesthesiologica Scandinavica: Fluid Resuscitation Guideline
- Perner. Scandinavian clinical practice guideline on choice of fluid in resuscitation of critically ill patients with acute circulatory failure. Acta Anaesthesiologica Scandinavica 2015;59:274–285
NEJM: Endovascular Stroke Therapy
- Full Text: Campbell. Endovascular Therapy for Ischemic Stroke with Perfusion-Imaging Selection. N Engl J Med 2015;epublished February 11th
- Full Text: Goyal. Randomized Assessment of Rapid Endovascular Treatment of Ischemic Stroke. N Engl J Med 2015;epublished February 11th
Journal of Trauma: EAST Guideline on Clearing the Cervical Spine in the Obtunded Patient
- Patel. Cervical Spine Collar Clearance in the Obtunded Adult Blunt Trauma Patient. J Trauma 2015;78(2):430-441
NEJM: Stroke Neuroprotection
- Abstract: Saver. Prehospital Use of Magnesium Sulfate as Neuroprotection in Acute Stroke (FAST-MAG study). N Engl J Med 2015;372:528-536
JAMA: Trauma Transfusion Ratios
Society of Critical Care Medicine Congress
JAMA: Paediatric Sedation
- Curley. Protocolized Sedation vs Usual Care in Pediatric Patients Mechanically Ventilated for Acute Respiratory Failure. A Randomized Clinical Trial (RESTORE Study). JAMA 2015;epublished January 20th
JAMA: Infection Control
Lancet Respiratory Medicine: Perioperative Goal-Directed Oxygen Delivery
- Ackland. Individualised oxygen delivery targeted haemodynamic therapy in high-risk surgical patients: a multicentre, randomised, double-blind, controlled, mechanistic trial (POM-O Study). Lancet Respir Med 2014;epublished December 15th
JAMA: Hypoxaemic Ischaemic Encephalopathy
- Shankaran. Effect of Depth and Duration of Cooling on Deaths in the NICU Among Neonates With Hypoxic Ischemic Encephalopathy: A Randomized Clinical Trial. JAMA 2014;312(24):2629-2639
New England Journal of Medicine: Endovascular Stroke Therapy
- Berkhemer. A Randomized Trial of Intraarterial Treatment for Acute Ischemic Stroke (MR CLEAN Trial). N Engl J Med 2014;epublished December 17th
New England Journal of Medicine: Traumatic Brain Injury
- Wright. Very Early Administration of Progesterone for Acute Traumatic Brain Injury (PROTECT III Trial) Investigators. N Engl J Med 2014;epublished December 10th
- Skolnick. A Clinical Trial of Progesterone for Severe Traumatic Brain Injury (SYNAPSE Trial). N Engl J Med 2014;epublished December 10th
Stroke: Statins for Subarachnoid Haemorrhage
- Wong. High-Dose Simvastatin for Aneurysmal Subarachnoid Hemorrhage: Multicenter Randomized Controlled Double-Blinded Clinical Trial. Stroke 2014;epublished December 16th
Lancet: Red Cell Transfusion Triggers
- Carson. Liberal versus restrictive blood transfusion strategy: 3-year survival and cause of death results from the FOCUS randomised controlled trial. Lancet 2014;epublished December 9th
Lancet: IV Fluid Therapy
- McNab. 140 mmol/L of sodium versus 77 mmol/L of sodium in maintenance intravenous fluid therapy for children in hospital (PIMS): a randomised controlled double-blind trial. Lancet 2014;epublished November 1st
Intensive Care Medicine: Therapeutic Hypothermia for Cardiac Arrest
Intensive Care Medicine: Intra-Cardiac Arrest Therapeutic Hypothermia
- Abstract: Debaty. Impact of intra-arrest therapeutic hypothermia in outcomes of prehospital cardiac arrest: a randomized controlled trial. Intensive Care Med 2014;40(12):1832-1842
Lancet: Mechanical Chest Compression Device
- Abstract: Perkins. Mechanical versus manual chest compression for out-of-hospital cardiac arrest (PARAMEDIC): a pragmatic, cluster randomised controlled trial. Lancet 2014;epublished November 16th
Intensive Care Medicine: Post Cardiac Arrest Prognostication
- Full Text: Sandroni. Prognostication in comatose survivors of cardiac arrest: An advisory statement from the European Resuscitation Council and the European Society of Intensive Care Medicine. Intensive Care Med 2014;epublished November 15th
Intensive Care Medicine: Shock & Haemodynamic Monitoring Guideline
- Full Text: Cecconi. Consensus on circulatory shock and hemodynamic monitoring. Task force of the European Society of Intensive Care Medicine. Intensive Care Med 2014;epublished November 13th
New England Journal of Medicine: Ebola
Intensive Care Medicine: Balanced Crystalloid Solutions
- Full Text: Shaw. Association between intravenous chloride load during resuscitation and in-hospital mortality among patients with SIRS. Intensive Care Med 2014;epublished October 8th
Cell Transplantation: Spinal Cord Regeneration
- Full Text: Tabakow. Functional regeneration of supraspinal connections in a patient with transected spinal cord following transplantation of bulbar olfactory ensheathing cells with peripheral nerve bridging. Cell Transplantation 2014;epublished October 21st
Resuscitation: Refractory Cardiac Arrest
- Full Text: Stub. Refractory Cardiac Arrest Treated with Mechanical CPR, Hypothermia, ECMO and Early Reperfusion (the CHEER Trial). Resuscitation 2014;epublished September 30th
Journal of Clinical Epidemiology: Fragility Index
- Full Text: Walsha. The statistical significance of randomized controlled trial results is frequently fragile: a case for a Fragility Index. Journal of Clinical Epidemiology 2014;67(6):622-628
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:
- groups were similar at baseline
- 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
- 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
- ICU stay
- 90 day mortality
- 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
- vasopressors
- greater fluid administration in the first 6 hours
- Full Text: The ARISE Investigators. Goal-Directed Resuscitation for Patients with Early Septic Shock. New Engl J Med 2014;epublished October 1st
- Vodcast: Presentation & Interview with Chief Investigator Sandra Peake
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
- both groups were similar at baseline (≤ 7 g/d vs <9 g/dL)
- SOFA median 10 vs 10; SAPS II median 51 vs 52
- the more restrictive transfusion trigger was associated with
- less units of transfused red cells (median/IQR)
- 1 (0-3) vs 4 (2-4)
- less units of transfused red cells (median/IQR)
- 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
- 90 day mortality
- Full Text: Holst. Lower versus Higher Hemoglobin Threshold for Transfusion in Septic Shock. TRISS Trial Group and the Scandinavian Critical Care Trials Group. New Engl J Med 2014;epublished October 1st
- Editorial: Hebert. Transfusion Threshold of 7 g per Deciliter — The New Normal. New Engl J Med 2014;epublished October 1st
- Vodcast: Interview with Chief Investigator Lars Holst
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:
- groups were similar at baseline
- 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
- 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
- thrombosis
New England Journal of Medicine: CALORIES
- Full Text: Harvey. Trial of the Route of Early Nutritional Support in Critically Ill Adults (CALORIES Study). New Engl J Med 2014;epublished October 1st
- Editorial: Cook. The Route of Early Nutrition in Critical Illness. New Engl J Med 2014;epublished October 1st
- Vodcast: Presentation and Interview with Chief Investigator Kathy Rowan
Journal of the American Medical Association: SDD vs SOD
- Full Text: Oostdijk. Effects of Decontamination of the Oropharynx and Intestinal Tract on Antibiotic Resistance in ICUsA Randomized Clinical Trial. JAMA 2014;epublished October 1st
- Editorial: Kollef. Rational Use of Antibiotics in the ICU. Balancing Stewardship and Clinical Outcomes. JAMA 2014;epublished October 1st
- Vodcast: Presentation and Interview with Chieft Investigator Evelien Oostdijk
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:
- 475 patients were included in the final analysis (vit D n=237; placebo n=238)
- 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
- hospital
- length of hospital stay
- 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
- length of hospital stay
- 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
- hospital mortality
- no significant differences in
- Full Text: Amrein. Effect of High-Dose Vitamin D3 on Hospital Length of Stay in Critically Ill Patients With Vitamin D DeficiencyThe VITdAL-ICU Randomized Clinical Trial. JAMA 2014;epublished September 30th
- Vodcast: Presentation and Interview with Chief Investigator Karin Amrein
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:
- most patients had either community-acquired pneumonia (≈60%) or hospital-acquired pneumonia (≈10%)
- 77% had a PaO2 /FiO2 < 200 mmHg
- 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
- SOT 46.8 % vs HFNO 37.7% vs NIV/HFNO 50%; p=0.17
- 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
- ICU mortality
- Full Text: McAuley. Simvastatin in ARDS. New Engl J Med 2014;epublished September 30th
- Full Text: Bove. Effect of Fenoldopam on Use of Renal Replacement Therapy Among Patients With Acute Kidney Injury After Cardiac Surgery: A Randomized Clinical Trial. JAMA 2014;epublished September 29th
New England Journal of Medicine: Ebola Virus Disease
- Full Text: WHO Ebola Response Team. Ebola Virus Disease in West Africa — The First 9 Months of the Epidemic and Forward Projections. New Engl J Med 2014;epublished September 23rd
Critical Care Medicine: Fatty Acid Supplementation
- Abstract: Grau-Carmona. Influence of n-3 Polyunsaturated Fatty Acids Enriched Lipid Emulsions on Nosocomial Infections and Clinical Outcomes in Critically Ill Patients: ICU Lipids Study. Crit Care Med 2014;epublished September 15th
Anesthesiology: Erythropoietin & Acute Kidney Injury
- Abstract: Dardashti. Erythropoietin and Protection of Renal Function in Cardiac Surgery (the EPRICS Trial). Anesthesiology 2014;121(3):582-590
European Heart Journal: STEMI
- Full Text: Schulz. Prasugrel plus bivalirudin vs. clopidogrel plus heparin in patients with ST-segment elevation myocardial infarction. Eur Heart J 2014;35(34):2285-2294
- Abstract: Montalescot. Early eplerenone treatment in patients with acute ST-elevation myocardial infarction without heart failure: The Randomized Double-Blind Reminder Study (REMINDER Study). Eur Heart J 2014;35:2295-2302
European Heart Journal: Guidelines
- Ristić. Triage strategy for urgent management of cardiac tamponade: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J 2014;35(34):2279-2284
European Journal of Anaesthesiology: Cardiovascular Assessment & Management for Non-Cardiac Surgery
- Kristensen. 2014 ESC/ESA Guidelines on non-cardiac surgery: cardiovascular assessment and management: The Joint Task Force on non-cardiac surgery: cardiovascular assessment and management of the European Society of Cardiology (ESC) and the European Society of Anaesthesiology (ESA). Eur J Anaesthesiol 2014;517-573
Canadian Medical Association Journal: Melatonin for Delirium
- Full Text: de Jonghe. Effect of melatonin on incidence of delirium among patients with hip fracture: a multicentre, double-blind randomized controlled trial. CMAJ 2014;epublished September 2nd
ESC Congress Studies
- Full Text: Fox. Ivabradine in Stable Coronary Artery Disease without Clinical Heart Failure (SIGNIFY Study). New Engl J Med 2014;epublished August 31st
- Full Text: Montalescot. Prehospital Ticagrelor in ST-Segment Elevation Myocardial Infarction (ATLANTIC study). New Engl J Med 2014;epublished September 1st
- Full Text: Lagerqvist. Thrombus Aspiration for Myocardial Infarction. New Engl J Med 2014;epublished September 1st
- Full Text: De Bruyne. Fractional Flow Reserve and PCI. New Engl J Med 2014;epublished September 1st
ESC Congress Studies
- Full Text: McMurray. Angiotensin–Neprilysin Inhibition versus Enalapril in Heart Failure (PARADIGM-HF trial). New Engl J Med 2014;epublished August 30th
- Full Text: Imazio. Colchicine for Prevention of Postpericardiotomy Syndrome and Postoperative Atrial Fibrillation. The COPPS-2 Randomized Clinical Trial. JAMA 2014;epublished August 30th
- Full Text: O'Donoghue. Effect of Darapladib on Major Coronary Events After an Acute Coronary SyndromeThe SOLID-TIMI 52 Randomized Clinical Trial. JAMA 2014;epublished August 31st
European Heart Journal: ESC Guidelines
- Konstantinides. 2014 ESC Guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J 2014;epublished August 29th
- Windecker. 2014 ESC/EACTS Guidelines on myocardial revascularization. Eur Heart J 2014;epublished August 29th
- Erbel. 2014 ESC Guidelines on the diagnosis and treatment of aortic diseases. Eur Heart J 2014;epublished August 29th
Infection Control and Hospital Epidemiology: Healthcare-Associated Infection Guidelines
- Yokoe. Introduction to "A Compendium of Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals: 2014 Updates". Infect Control Hosp Epidemiol 2014;35(S2):S21-S31
- Marschall. Strategies to Prevent Central Line–Associated Bloodstream Infections in Acute Care Hospitals: 2014 Update. Infect Control Hosp Epidemiol 2014;35(7):753-771
- Lo. Strategies to Prevent Catheter-Associated Urinary Tract Infections in Acute Care Hospitals: 2014 Update. Infect Control Hosp Epidemiol 2014;35(S2):S32-47
- Dubberke. Strategies to Prevent Clostridium difficile Infections in Acute Care Hospitals: 2014 Update. Infect Control Hosp Epidemiol 2014;35(S2):S48-56
- Anderson. Strategies to Prevent Surgical Site Infections in Acute Care Hospitals: 2014 Update. Infect Control Hosp Epidemiol 2014;35(S2):S66-88
- Marschall. Strategies to Prevent Central Line–Associated Bloodstream Infections in Acute Care Hospitals: 2014 Update. Infect Control Hosp Epidemiol 2014;35(S2):S89-107
- Calfee. Strategies to Prevent Methicillin-Resistant Staphylococcus aureus Transmission and Infection in Acute Care Hospitals: 2014 Update. Infect Control Hosp Epidemiol 2014;35(S2):S108-132
- Klompas. Strategies to Prevent Ventilator-Associated Pneumonia in Acute Care Hospitals: 2014 Update. Infect Control Hosp Epidemiol 2014;35(S2):133-S154
- Ellingson. Strategies to Prevent Healthcare-Associated Infections through Hand Hygiene. Infect Control Hosp Epidemiol 2014;35(S2):S155-S178
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
- Editorial: Dellinger. Crystalloids for Fluid Resuscitation in Sepsis: Where Is the Balance? 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)
- an increase in the number of
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:
- no interaction between erythropoietin and hemoglobin transfusion threshold
- 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
- between placebo and erythropoietin
- 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:
- 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
- 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:
- 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%
- incidence of favourable modified Rankin Scale (mRS) score, obtained by questionnaire at 6 months (1° outcome)
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:
- 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)
- morbidity on day 7
- a trend towards a reduction in composite outcome of 30-day complications and mortality (1° outcome)
- 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
- hospital / 28-day / 30-day
- fewer complications
- perioperative goal-directed therapy was associated with
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:
- 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%)
- KPNC cohort
- 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.
- of 14, 206 inpatient deaths
- 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%)
- of 143,312 deaths
- KPNC cohort
- 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
- patients with sepsis meeting criteria for EGDT (n = 2,536)
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:
- the study was stopped early for futility
- 745 out of a planned 1000 patients were recruited
- both groups were similar for
- demographics
- physiology
- 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
- 60-day in-hospital mortality
- 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)
- renal failure to day 14
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:
- 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%)
- 2973 patients (29·5%) had sepsis on admission or during the ICU stay
- mortality rates
- 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)
- 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)
- a stepwise increase in the adjusted risk of in-hospital death according to decrease in global national income
- Abstract: Vincent. Assessment of the worldwide burden of critical illness: the Intensive Care Over Nations (ICON) audit. Lancet Respiratory Medicine 2014;epublished April 14th
- Commentary: Cerro. Global analysis of critical care burden. Lancet Respiratory Medicine 2014;epublished April 14th(free registration required)
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:
- 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
- increased 90-day mortality
- 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)
- duration
- increased
- modified Glasgow Coma Scale score at 72 hours (10 [8-11] vs 7 [4-9], p < 0.001)
- decreased
- Abstract: Kumar. Randomized Controlled Trial Comparing Cerebral Perfusion Pressure-Targeted Therapy Versus Intracranial Pressure-Targeted Therapy for Raised Intracranial Pressure due to Acute CNS Infections in Children. Critical Care Med 2014;epublished April 1st
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:
- 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
- extracranial bleeding
- reduced rate of death or haemodynamic decompensation (1° outcome)
- 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)
- day 7
- Abstract: Meyer. Fibrinolysis for Patients with Intermediate-Risk Pulmonary Embolism (PEITHO study). N Engl J Med 2014;370:1402-1411
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:
- 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
- of the 1° outcome components, only hospitalization for heart failure had a significantly lower incidence in the spironolactone group
- 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%
- higher rate of hyperkalemia
- no significant differences in the
- incidence of serious adverse events
- serum creatinine level of 265 μmol/l (3.0 mg/dl) or higher
- dialysis
- Abstract: Pitt. Spironolactone for Heart Failure with Preserved Ejection Fraction (TOPCAT study). N Engl J Med 2014;370:1383-1392
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:
- 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
- ICU mortality
- mechanical devices, in comparison with no VTE prophylaxis, were not associated with a reduced mortality risk
- 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
- ICU sub-hazard ratio
- prophylactic anticoagulation was associated with a lower risk of death than those receiving only mechanical device prophylaxis
- Abstract: Lilly. Thrombosis Prophylaxis and Mortality Risk among Critically Ill Adults. Chest 2014;epublished April 10th
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:
- baseline data
- median age of 61 years (IQR 51—71)
- assessment post discharge
- 448 patients at 3 months
- 382 patients at 12 months
- 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
- depressive symptoms were common among individuals without a history of depression
- 30% at 3 months
- 29% at 12 months
- post-traumatic distress disorder was present in
- 7% at 3 and 12 months
- 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
- basic activities of daily living
- Abstract: Jackson. Depression, post-traumatic stress disorder, and functional disability in survivors of critical illness in the BRAIN-ICU study: a longitudinal cohort study. Lancet Respiratory Medicine 2014;epublished April 7th
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:
- 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
- increased major bleeding with aspirin
- 4.6% vs 3.8%, hazard ratio 1.23; 95% CI 1.01 to 1.49; P=0.04
- no differences in 1° or 2° outcomes between aspirin strata
- Full Text: Devereaux. Aspirin in Patients Undergoing Noncardiac Surgery (POISE-2 Trial). New Engl J Med 2014;epublished March 31st
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:
- 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
- the primary endpoint, a composite of death or nonfatal myocardial infarction at 30 days
- 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
- myocardial infarction
- Abstract: Devereaux. Clonidine in Patients Undergoing Noncardiac Surgery (POISE 2 trial). N Engl J Med 2014;epublished March 31st
March 2014
New England Journal of Medicine: Stroke Hemicraniectomy
- Abstract: Jüttler. Hemicraniectomy in Older Patients with Extensive Middle-Cerebral-Artery Stroke (Destiny II). N Engl J Med 2014;370:1091-1100
PLoS One: Acute Respiratory Distress Syndrome
- Full Text: Cornet. Recombinant human activated protein C in the treatment of acute respiratory distress syndrome: a randomized clinical trial. PLoS One 2014;14;9(3):e90983
European Heart Journal: Myocardial Infarction
- Full Text: Siddiqi. Intravenous sodium nitrite in acute ST-elevation myocardial infarction: a randomized controlled trial (NIAMI). Eur Heart J 2014;epublished March 17th
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:
- protocol-based early goal-directed therapy (n=439, based on the Rivers GDT protocol)
- protocol-based standard therapy (not requiring the placement of a central venous catheter, administration of inotropes, or blood transfusions, n=446)
- usual care (n=456)
and found:
- 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.
- 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
- There were no significant differences in
- 90-day mortality
- 1-year mortality
- need for organ support
- Full Text: The ProCESS Investigators. A Randomized Trial of Protocol-Based Care for Early Septic Shock (ProCESS study). New Engl J Med 2014;epublished March 18th
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:
- 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
- high target group 36.6% versus low target group 34.0%
- 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
- high target group 43.8% versus low target group 42.3%
- 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
- 28 day mortality
- Full Text: Asfar. High versus Low Blood-Pressure Target in Patients with Septic Shock (SEPSISPAM study). New Engl J Med 2014;epublished March 18th
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:
- 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
- albumin group 31.8% versus crystalloid group 32.0%
- 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
- albumin group 41.1% versus crystalloid group 43.6%
- 28 day mortality (primary outcome)
- no significant differences in other secondary outcomes
- organ dysfunction:
- number of patients
- degree of dysfunction
- length of stay
- hospital
- organ dysfunction:
- during the first 7 days, albumin therapy was associated with
- higher mean arterial pressure (P=0.03)
- lower net fluid balance (P<0.001)
- no significant difference in total daily administered fluid (P=0.10)
- Full Text: Caironi. Albumin Replacement in Patients with Severe Sepsis or Septic Shock (ALBIOS study). New Engl J Med 2014;epublished March 18th
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:
- 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
- overall mortality decrease of 16.7% (95% CI 14.8% to 18.6%)
- an annual rate of absolute decrease of 1.3%
- relative risk reduction of 47.5% (95% CI 44.1% to 50.8%)
- 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)
- 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
- 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
- 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
- in the absence of comorbidities and older age, mortality was less than 5%
- Full Text: Kaukonen. Mortality Related to Severe Sepsis and Septic Shock Among Critically Ill Patients in Australia and New Zealand, 2000-2012. JAMA 2014;epublished March 18th
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:
- 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
- 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%
- sustained ROSC (emergency department admittance)
- 20 minutes CPR fraction
- iA-CPR 80.4% vs M-CPR: 80.2%
- Abstract: Wik. Manual vs. integrated automatic load-distributing band CPR with equal survival after out of hospital cardiac arrest. The randomized CIRC trial. Resuscitation 2014;epublished March 15th
Nephrology Dialysis Transplantation: Hyponatraemia Guideline
- Spasovski. Clinical practice guideline on diagnosis and treatment of hyponatraemia. Nephrol Dial Transplant 2014;0:1–39
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:
- 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)
- a lower incidence of delirium (3% vs 32%; RR 0.09, 95% CI 0.01 to 0.069; p=0.003)
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:
- the study was stopped after the recruitment of 79 patients
- success at NGT placement
- in the presence of cricoid pressure - 0%
- in the absence of cricoid pressure - 100%
- oesophageal patency was observed
- in the presence of cricoid pressure - 0%
- in the absence of cricoid pressure - 100%
- 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:
- 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)
- 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
- 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:
- 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)
- 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)
- 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
- Abstract: Mahjoub. Evaluation of pulse pressure variation validity criteria in critically ill patients: a prospective observational multicentre point-prevalence study. Br J Anaesth 2013;epublished December 29th
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:
- 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
- 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
- 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
- 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
- Editorial: Rittenberger. Temperature Management and Modern Post–Cardiac Arrest Care. N Eng 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:
- 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
- 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%)
- VF patients (P=0.69)
- 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%)
- VF patients (P=0.69)
- 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
- increased rearrest in the field (P=0.008)
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
- Editorial: Granger. Randomized Clinical Trial Progress to Inform Care for Out-of-Hospital Cardiac Arrest. 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:
- 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
- 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%
- intensive care unit discharge
- 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:
- 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%
- at 6 - 8 days (P=0.31)
- 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.
- Commentary: Stiles. Nitrites No Cure for Reperfusion Injury From MI Stenting. Medscape 2013;epublished November 17th(free registration required)
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:
- 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
- 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
- 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
- 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
Journal of the American College of Cardiology: Cardiovascular Risk
- Goff. 2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;():
October 2013
Canadian Journal of Anaesthesia: Difficult Airway
- Law. The difficult airway with recommendations for management – Part 1 – Difficult tracheal intubation encountered in an unconscious/induced patient. Can J Anesth 2013;60:1089-1118
- Law. The difficult airway with recommendations for management – Part 2 – The anticipated difficult airway. Can J Anesth 2013;60:1119-1138
Canadian Journal of Anaesthesia: Difficult Airway
- Law. The difficult airway with recommendations for management – Part 1 – Difficult tracheal intubation encountered in an unconscious/induced patient. Can J Anesth 2013;60:1089-1118
- Law. The difficult airway with recommendations for management – Part 2 – The anticipated difficult airway. Can J Anesth 2013;60:1119-1138
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:
- the overall compliance rate in both groups was 91%
- regarding fluid therapy
- no apparent difference in administered volume (intervention 4190 ml versus control 4024 ml)
- the intervention group received more colloid (colloid therapy was part of the interventional protocol)
- 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)
- primary outcome
- 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:
- 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)
- 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
- Editorial: Seymour. Making a Pragmatic Choice for Fluid Resuscitation in Critically Ill Patients. 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:
- mean APACHE II score was 23.5 (95% CI 21.9-25.2)
- 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)
- 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%)
- 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)
- myofiber necrosis occurred in 20 of 37 patients (54.1%).
- 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:
- targeted heart rates were achieved in all patients in the esmolol group compared with those in the control group
- 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:
- the study was stopped for futility at the first scheduled interim analysis
- 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%)
- 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%)
- 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:
- 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)
- 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
- Editorial: Brilakis. Patient With Coronary Stents Needs Surgery: What to Do? 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:
- 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
- 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
- Commentary: Malani. Preventing Infections in the ICU: One Size Does Not Fit All. JAMA 2013;epublished October 4th
- Video Interview: Prof Harris Discusses his study "Universal Glove and Gown Use and Acquisition of Antibiotic-Resistant Bacteria in the ICU: A Randomized Trial"
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:
- cognitive impairment was present in 6% at baseline
- delirium developed in 74% during the hospital stay
- 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)
- 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
- 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)
- 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:
- 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)
- 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)
- 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: 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
- Tenner. American College of Gastroenterology Guideline: Management of Acute Pancreatitis. Am J Gastroenterol 2013;108:1400-1415
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:
- 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
- Editorial: Hylek. Dabigatran and Mechanical Heart Valves — Not as Easy as We Hoped. 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:
- 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).
- 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)
- 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)
- 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:
- 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)
- 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)
- 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)
- 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
- Editorial: Byrne. Unmet Aspirations — Where To Now for Catheter Thrombectomy? New Eng J Med 2013;epublished September 1st
- Commentary: Lauer. The Randomized Registry Trial — The Next Disruptive Technology in Clinical Research? 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:
- 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)
- 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)
- 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
- Editorial: Keaney. P2Y12 Inhibition in Patients with NSTEMI — Can Later Be Better? 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:
- after a mean follow up of 23 months, the trial was terminated early by the data and safety monitoring committee
- 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)
- 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
- Editorial: Mauri. Nonculprit Lesions — Innocent or Guilty by Association. 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:
- 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)
- 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:
- 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)
- no differences in secondary outcomes, including procedural thrombotic complications
- 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:
- 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)
- Numerically more oversedation with haloperidol (11 patients versus 6)
- No difference in rates of QTc prolongation (haloperidol 7 patients versus placebo 6).
- 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
- Original Study: 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 2012;307(8):795-803
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
- Retter. Guidelines on the management of anaemia and red cell transfusion in adult critically ill patients. British Committee for Standards in Haematology. Br J Haematol 2013;160(4):445-64
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
- Editorial: Frontera. Blood Pressure in Intracerebral Hemorrhage — How Low Should We Go? 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
- Editorial: Edmond. Screening Inpatients for MRSA — Case Closed. 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
- Editorial: Sin. Steroids for Treatment of COPD Exacerbations: Less Is Clearly More. 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
- Editorial: Azoulay. Music Therapy for Reducing Anxiety in Critically Ill Patients. 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
- Editorial: Ochoa Gautier. Early Nutrition in Critically Ill Patients: Feed Carefully and in Moderation. 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
- Editorial: Soo Hoo. In Prone Ventilation, One Good Turn Deserves Another. 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
- Kozek-Langenecker. Management of severe perioperative bleeding: Guidelines from the European Society of Anaesthesiology. Eur J Anaesthesiol 2013;30:270–382
April 2013
Critical Care: European Haemorrhage Guideline
- Spahn. Management of bleeding and coagulopathy following major trauma: an updated European guideline. Critical Care 2013;17:R76
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
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
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.
Critical Care Medicine: Surviving Sepsis Campaign Guidelines 2012
- Dellinger. Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2012. Crit Care Med 2013;41:580–637
Critical Care Medicine: Pain, Agitation & Delirium
- Barr. Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the Intensive Care Unit. Crit Care Med 2013; 41:263–306
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 Text: Díaz-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
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).
Abstract: Morrison. 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 difficile–associated 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.
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
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
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
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