Newsletter 98 / October 20th 2013




Welcome to the 98th Critical Care Reviews Newsletter, bringing you the best critical care research published in the past week, plus a wide range of free full text review articles and guidelines from over 300 clinical and scientific journals. It's a small newsletter this week, reflecting a relative paucity of publications over the past 7 days.

In news, the World Medical Association mark the 50th anniversary of the Declaration of Helsinki with the release of its 7th revision, published yesterday. This week's research studies include randomized controlled trials investigating quality of life after coronary revascularization, MARS therapy, and prothrombin complex concentrate. Meta analyses examine nitric oxide and selenium, while observational studies evaluate central venous catheterization infection risk, early parenteral nutrition, carbapenamase-producing bacteria, out-of-hospital cardiac arrest, cost of dialysis, tension pneumothorax and anaphylaxis.

There are editorials on carabpenemase-prodcuing bacteria and impact factor, as well as commentaries on peer review and gastric varices. This week there is a single guideline, from the European Society of Cardiology, concerning diabetes.

Amongst the clinical review articles are papers on viral myocarditis, COPD, acute liver injury, hypoglycaemia, meningococcal disease, aspergillosis, and post-surgical complications.

The topic for This Week's Papers is septic shock, starting with a paper on its pathogenesis in tomorrow's Paper of the Day.


There are three meetings coming up that might be of interest to you:

Critical Care Reviews Meeting January 24th, 2014 - Belfast, Northern Ireland

  • If you are in Ireland or Great Britain (or a short flight away), Critical Care Reviews will be hosting it's second meeting outside Belfast, Northern Ireland. It's an all-day event with a fantastic programme consisting of local intensivists, local non-critical care specialists, and outstanding international guest speakers. The programme has been finalised and approved for 5 CPD points by the Royal College of Anaesthetists. Registration is now open. 


Intensive Care Society State-of-the-Art Meeting, December  16th - 18th, London

  • The ICS will be holding their annual State-of-the-Art meeting in London this December. It's the largest meeting of its kind in the UK and attracts a host of big names from the world of critical care.


SMACC GOLD March 19-21st, 2014 Gold Coast, Queensland, Australia

  • This major international conference, also in it's second year, is a must for those active in the online critical care community. Webmasters of the most prominent critical care websites and blogs will descend on the beautiful Gold Coast for an amazing get together of like-minded people in a totally different style of conference. Registration is currently open.



Journal of the American Medical Association:     Declaration of Helsinki



Interventional Trials

Journal of the American Medical Association:     Coronary Revascularization

In a further analysis of the FREEDOM trial, Abdallah and colleagues compared the health status of diabetic patients with multivessel coronary artery disease who underwent revascularization with either CABG (n=935) or PCI (n=945), and found:

  1. at 2 years, there were small but statistically significant improvements with CABG over PCI (mean (SD))
    • angina frequency: 96.0 (11.9) versus 94.7 (14.3); mean treatment benefit 1.3 (95% CI 0.3-2.2); P < 0.01 
    • physical limitations: 87.8 (18.7) versus 86.0 (19.3); mean treatment benefit 4.4 (95% CI 2.7-6.1); P < 0.01
    • quality-of-life subscales of the Seattle Angina Questionnaire:  82.2 (18.9) versus 80.4 (19.6); mean treatment benefit 2.2 (95% CI 0.7-3.8); P < 0.01
      • for each scale, scores range from 0 to 100, with higher scores representing better health
  2. after 2 years, both interventions had similar outcomes

Abstract:  Abdallah. Quality of Life After PCI vs CABG Among Patients With Diabetes and Multivessel Coronary Artery Disease. A Randomized Clinical Trial. JAMA 2013;310(15):1581-1590 


Annals of Internal Medicine:     MARS

Saliba and colleagues compared albumin dialysis with the Molecular Adsorbent Recirculating System (MARS, n=53) with standard therapy (n=49) in French patients with acute liver failure, stratified according to whether paracetamol induced or not, and found:

  1. in the modified intention-to-treat population:
    • demographics:
      • 102 patients
      • mean age 40.4 years (SD 13) 
    • there was no difference in six-month survival (P = 0.28)
      • MARS: 84.9% (95% CI 71.9% - 92.8%)
      • standard therapy 75.5% (95% CI 60.8% to 86.2%) 
    • in patients with paracetamol-related ALF, there was also no difference in 6-month survival rate (P = 0.46) 
      • MARS 85.0% (95% CI 61.1% - 96.0%)
      • standard therapy 68.4% (95% CI 43.5% - 86.4%)
  2. in the per-protocol analysis
    • there was no difference in six-month survival (P = 0.50)
      • MARS (n=39) 82.9% (95% CI 65.9% - 91.9%) (at least 1 MARS session ≥ 5 hours)
      • standard therapy (n=49) 75.5% (95% CI 60.8% - 86.2%)
  3. 66 of 102 patients had transplantation (41.0% among paracetamol-induced ALF; 79.4% among non–paracetamol-induced ALF; P < 0.001)
  4. a short delay from randomization to liver transplantation (median 16.2 hours) precluded definitive efficacy or safety evaluations
  5. there was no difference in adverse between therapies

Abstract:  Saliba. Albumin Dialysis With a Noncell Artificial Liver Support Device in Patients With Acute Liver Failure: A Randomized, Controlled Trial. Ann Intern Med 2013;159(8):522-531 


Circulation:     Prothrombin Complex Concentrate

Sarode and colleagues completed a phase IIIb, multicenter, open-label, noninferiority trial in 202 nonsurgical patients (intention-to-treat efficacy population) receiving vitamin K antagonist anticoagulants and having a major haemorrhage, comparing nonactivated 4-factor prothrombin complex concentrate (4F-PCC, n=98) with plasma (n=104) for urgent vitamin K antagonist reversal, and found:

  1. baseline international normalized ratios (median (range))
    • 4F-PCC group  3.90 (1.8–20.0)
    • plasma group: 3.60 (1.9–38.9)
  2. no difference in achievement of effective hemostasis, demonstrating noninferiority (difference 7.1%; 95% CI –5.8 to 19.9)
    • 4F-PCC:  72.4%
    • plasma:  65.4%
  3. more rapid INR reduction with 4F-PCC, demonstrating 4F-PCC superiority (difference 52.6%; 95% CI 39.4 to 65.9)
    • 4F-PCC:  62.2% 
    • plasma:  9.6%
  4. higher assessed coagulation factors with 4F-PCC therapy from 0.5 to 3 hours after infusion start (P<0.02)
  5. no difference in safety profiles (adverse events, serious adverse events, thromboembolic events, and deaths), with similar numbers experiencing ≥1 adverse event
    • 4F-PCC:  66 of 103
    • plasma:  71 of 109

Full Text:  Sarode. Efficacy and Safety of a 4-Factor Prothrombin Complex Concentrate in Patients on Vitamin K Antagonists Presenting With Major Bleeding: A Randomized, Plasma-Controlled, Phase IIIb Study.  Circulation. 2013 Sep 10;128(11):1234-43 


Meta Analysis

Critical Care Medicine:     Nitric Oxide

Adhikari and colleagues updated a previous meta analysis, including 9 studies (n=1,142), appraising the efficacy of inhaled nitric oxide in patients with severe ARDS (PaO2/FiO2 <= 100 mm Hg), but not patients with mild-moderate ARDS (100 < PaO2/FIO2 <= 300 mm Hg), at the time of randomization, and found:

  1. nitric oxide did not reduce mortality in 
    • severe ARDS (RR 1.01, 95% CI 0.78-1.32; p = 0.93; n = 329, six trials) 
    • mild-moderate ARDS (RR 1.12; 95% CI 0.89-1.42; p = 0.33; n = 740, seven trials)
  2. risk ratios were similar between subgroups (interaction p = 0.53)
  3. no between-trial heterogeneity in any analysis (I2 = 0%)
  4. varying the PaO2/FiO2 threshold between 70 and 200 mm Hg, in increments of 10 mm Hg, did not identify any threshold at which the nitric oxide-treated patients had lower mortality relative to controls

Abstarct:  Adhikari. Inhaled Nitric Oxide Does Not Reduce Mortality in Patients With Acute Respiratory Distress Syndrome Regardless of Severity: Systematic Review and Meta-Analysis. Crit Care Med 2013;epublished Oct 15th 


Journal of Critical Care:     Selenium

Landucci and colleagues pooled data from nine randmized controlled trials comparing selenium supplementation with standard therapy in critically ill adults, and found selenium administration was associated with:

  1. reduced
    • 28 day mortality (RR = 0.84, 95% CI 0.71–0.99, P = 0.04)
  2. no effect on
    • 6-month mortality (2 studies)
    • hospital length of stay
    • pulmonary infections
    • renal failure

Abstract:  Landucci. Selenium supplementation in critically ill patients: A systematic review and meta-analysis. J Crit Care 2013;epublished October 16th


Observational Studies

American Journal fo Respiratory and Critical Care Medicine:     Central Venous Catherisation

Timsit and colleagues reviewed data from 2 multicenter studies (2,527 catheters and 19,481 catheter-days), comparing femoral and internal jugular vein central venous catheterisation for the risks of catheter-related-bloodstream infection, major-catheter-related infection and catheter-tip colonization, and found:
  1. no difference in 
    • catheter-related-bloodstream infection (internal jugular 1.0 versus femoral 1.1/1000-catheter-days, HR 0.63, 95% CI 0.25 - 1.63; p=0.34)
    • major-catheter-related infection (internal jugular 1.8 versus femoral 1.4/1000-catheter-days, HR 0.91, 0.38 - 2.18; p=0.34)
    • colonization (internal jugular 11.6 vs. femoral 12.9/1000-catheter-days, HR 0.80, 0.25 - 1.63; p=0.15)
  2. colonization was higher with femoral catheterization
    • for females (HR 0.39, 95% CI 0.24 - 0.63, p<0.001)
    • when maintained for more than 4 days (HR 0.73, 95% CI 0.53 to 1.01, p=0.05)
  3. chlorhexidine impregnated dressings reduced differences in cutaneous and catheter colonization between internal jugular and femoral vein catheterization

Abstract:  Timsit. Jugular vs. Femoral Short-Term Catheterization and Risk of Infection in ICU Patients: Causal Analysis of 2 Randomized Trials. Am J Respir Crit Care 2013; epublished October 15th 


Lancet Respirtory Medicine:     Early Parenteral Nutrition

In a prospectively planned subanalysis of the EPaNIC trial, Hermans and colleagues examined whether early (n=295) or late (n=305) parenteral nutrition differentially affected muscle weakness and autophagic quality control of myofibres in 600 awake, cooperative patients, and found late parenteral nutrition was associated with: 
  1. less weakness on first assessment (median day 9 post-randomisation)
    • 34% versus 43%; absolute difference −9%, 95% CI −16 to −1; p=0·030
  2. faster recovery from weakness (p=0·021)
  3. improved autophagosome formation based on
    • higher LC3 (microtubule-associated protein light chain 3) II to LC3I ratio (p=0·026)
    • with values almost double those in the healthy control group (p=0·0016)
    • coinciding with less ubiquitin staining (p=0·019) 
  4. myofibre cross-sectional area was less and density was lower in critically ill patients than in healthy controls, similarly with early PN and late PN
  5. expression of mRNA encoding contractile myofibrillary proteins was lower and E3-ligase expression higher in muscle biopsies from patients than in control participants (p≤0·0006), but was unaffected by nutrition

Abstract:  Hermans. Effect of tolerating macronutrient deficit on the development of intensive-care unit acquired weakness: a subanalysis of the EPaNIC trial. The Lancet Respiratory Medicine 2013;1(8):621-629 


International Journal of Antimicrobial Agents:     Carbapenemase-Producing Bacteria

Pontikisa and colleagues completed a multicentre, prospective case-series of 68 consecutive patients with fosfomycin-susceptible extensively drug-resistant or pandrug-resistant Pseudomonas aeruginosa (n=41) or Klebsiella pneumoniae (n=17) carbapenemase-producing strains, and found:

  1. fosfomycin was administered intravenously at a median dose of 24 g/day for a median of 14 days, mainly in combination with colistin or tigecycline
  2. at day 14
    • 54.2% were successfully treated
    • 33.3% had therapeutc failure
    • 6.3% had an indeterminate outcome
    • 6.3% suffered superinfection
  3. 28-day mortality was 37.5%.
  4. bacterial eradication was observed in 56.3% of cases
  5. fosfomycin resistance developed in three cases
  6. the main adverse event was reversible hypokalaemia

Abstract:  Pontikisa. Outcomes of critically ill intensive care unit patients treated with fosfomycin for infections due to pandrug-resistant and extensively drug-resistant carbapenemase-producing Gram-negative bacteria. International Journal of Antimicrobial Agents 2013;epublished October 16th


Other studies of interest

Critical Care:     Out-of-Hospital Cardiac Arrest

Full Text:  Goto.  Termination-of-resuscitation rule for emergency department physicians treating out-of-hospital cardiac arrest patients: an observational cohort study. Critical Care 2013;17:R235


Nephrology Dialysis Transplantation:     Dialysis

Full Text:  Karopadi. Cost of peritoneal dialysis and haemodialysis across the world. Nephrol Dial Transplant 2013;28(10):2553-2569


Journal of Cardiothoracic Surgery:     Tension Pneumothorax

Abstract:  Yoon. Tension pneumothorax, is it a really life-threatening condition? Journal of Cardiothoracic Surgery 2013;8:197  


Allergy:     Anaphylaxis

Full Text:  Panesar. The epidemiology of anaphylaxis in Europe: a systematic review. Allergy 2013;epublished October 14th



European Heart Journal:    Diabetes Mellitus



Journal of the Scientific Society:     Impact Factor


Annals of Nigerin Medicine:     Carbapenemase-Producing Bacteria



Gastrointestinal Endoscopy:     Gastric Varices


Journal of the American Medical Association:     Peer Review


Review - Clinical


Middle East Journal of Anaesthesiology:     Airtraq



Open Journal of Anesthesiology:     Acute Normovolaemic Haemodilution


Methodist Debakey Cardiovascular Journal:     Myocardial Infarction Definition


Hellenic Journal of Cardiology:     Viral Myocarditis



Journal of Clinical Investigation:     COPD


Thorax:     Community-Acquired Pneumonia



Frontiers in Physiology:     Acute Liver Injury


International Journal of Hepatology:     Oncological Therapy-Induced Liver Injury


International Journal of Hepatology:     Extrahepatic Portal Venous Obstruction Bleeding



Journal of the Scientific Society:     Hypoglycaemia



Revista Brasileira de Anestesiologia:     Burns



Open Journal of Anesthesiology:     Thromboelastography



Arquivos de Neuro-Psiquiatria:     Meningococcal Disease


Journal of Antimicrobial Chemotherapy:     Aspergillosis


Digestive and Liver Disease:     Post-Surgical Complications


Revista Brasileira de Anestesiologia:     Practice of Anaesthesia


Indian Journal of Dermatology:     Acrocyanosis


Medical Gas Research:     Argon


Postgraduate Medical Journal:     Cancer Therapies



I hope you find these brief summaries and links useful.

Until next week