Newsletter 101 / November 10th 2013




Welcome to the 101st 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 big newsletter this week, with a lot of interesting, although not major, research published recently. There is also a host of commentaries and review articles, as well as a position statement and a couple of editorials. In addition, the topic for This Week's Papers is extracorporeal liver support, starting with a general paper in tomorrow's Paper of the Day.

For those preparing for critical care exams, hopefully in 4 to 6 weeks there should be a bank of free multiple choice question exams available on the site. 



It's just 5 weeks to the annual Intensive Care Society State-of-the-Art meeting in London, 11 weeks to the Critical Care Reviews meeting outside Belfast, and 18 weeks to SMACC gold in Australia. The deadline for SAMCC gold abstracts is Friday 22nd November.



Interventional Trials

American Journal of Respiratory and Critical Care Medicine:     Asthma

Busse and colleagues undertook a randomized, placebo-controlled trial, evaluating brodalumab (140, 210, or 280 mg), a human anti-IL-17 receptor A monoclonal antibody, in 302 subjects with inadequately controlled moderate-severe asthma taking regular inhaled corticosteroids, and found:

  1. both groups were similar at baseline
  2. there were no differences in treatment effects between groups
  3. in prespecified subgroup analysis, uncorrected for multiple testing, Asthma Control Questionnaire (ACQ) score was
    1. slightly improved in the high reversibility subgroup, 210 mg group (estimated treatment difference 0.53)
    2. not improved in the higher 280 mg group (estimated treatment difference 0.38)
  4. there was no difference in adverse effects

Abstract:  Busse. Randomized, Double-blind, Placebo-controlled Study of Brodalumab, a Human Anti-IL-17 Receptor Monoclonal Antibody, in Moderate to Severe Asthma. Am J Respir Crit Care Med 2013;epublished November 7th


Systematic Review & Meta Analysis

Chest:     Asthma

Morales and colleagues examined all randomised, blinded, placebo-controlled clinical trials evaluating acute beta-blocker exposure in asthmatic patients, and found:

  1. acute selective beta-blockers
    • decreased mean FEV1 by 6.9% (95% CI -8.5 to -5.2)
      • 1 in 8 patients had a decrease in FEV1 of ≥20% (P=0.03)
      • 1 in 33 patients were affected by symptoms (P=0.18)
    • attenuated concomitant beta2-agonist response by 10.2% (95% CI -14.0 to -6.4)
  2. acute non-selective beta-blockers
    • decreased mean FEV1 by 10.2% (95%CI -14.7 to -5.6)
      • 1 in 9 had a decrease in FEV1 of ≥20% (P=0.02)
      • 1 in 13 patients were affected by symptoms (P=0.14)
    • attenuated concomitant beta2-agonist response by 20.0% (95%CI -29.4 to -10.7)

Abstract:  Morales. Adverse respiratory effect of acute beta-blocker exposure in asthma: a systematic review and meta-analysis of randomized controlled trials. Chest 2013;epublished November 7th


JAMA Surgery:     IVC Filters

Haut and colleagues reviewed 8 controlled studies compared the effectiveness of no IVC filter vs IVC filter on PE, fatal pulmonary embolism, deep vein thrombosis, and/or mortality in trauma patients, and found:

  1. IVC filter placement was associated with
    • a consistent reduction of
      • PE (relative risk 0.20, 95% CI 0.06 to 0.70; I2 = 0%) 
      • fatal PE (relative risk 0.09, 95% CI 0.01 to 0.81; I2  = 0%)
    • no significant difference in the incidence of
      • deep vein thrombosis (relative risk 1.76, 95% CI 0.50 to 6.19; P = 0.38; I2 = 56.8%) 
      • mortality (relative risk 0.70, 95% CI 0.40 to 1.23; I2  = 6.7%)
  2. the number needed to treat to prevent 1 additional PE with IVC filters was estimated to range from 109 (95% CI 93 to 190) to 962 (95% CI 819 to 2565), depending on the baseline PE risk

Abstract: Haut. The Effectiveness of Prophylactic Inferior Vena Cava Filters in Trauma Patients: A Systematic Review and Meta-analysis.  JAMA Surg 2013;epublished November 6th


Journal of Neurotrauma:     Traumatic Brain Injury

Reljic and colleagues undertook a systematic review and proportional meta-analysis (41 studies, 13 prospective and 28 retrospective studies, n=10,501), examing the effects of repeat CT brain on the incidence of altered management (intracranial intervention, change in intracranial pressure monitoring, and/or administration of drug therapy) in traumatic brain injury, and found:

  1. repeat CT brain changed management in
    • 11.4% (95% CI 5.9-18.4; 13 prospective studies)
    • 9.6% (95% CI 6.5-13.2, 28 retrospective studies)
  2. in a subgroup analysis of mild TBI patients (Glasgow Coma Scale score 13 to 15)
    • 2.3% (95% CI 0.3-6.3; 5 prospective studies)
    • 3.9% (95% CI 2.3-5.7; 9 retrospective studies)

Abstract:  Reljic. Value of Repeat Head Computed Tomography after Traumatic Brain Injury: Systematic Review and Meta-Analysis. J Neurotrauma 2013;epublished November 7th


PLoS One:     Stroke

Lin and colleagues compared the benefits and safety of endovascular treatment with intravenous thrombolysis for the treatment of acute ischemic stroke (5 randomized, controlled trials, n=1,106), and found:

  1. no difference in the incidence of
    • good outcomes (ET: 43.06% vs IT: 41.78%; OR 1.14; 95% CI 0.77 to 1.69; P=0.52)
    • excellent outcomes (ET: 30.43% vs IT: 30.42%; OR 1.05; 95% CI 0.80 to 1.38; P=0.72)
  2. endovascular therapy was not associated with increased
    • symptomatic hemorrhage (ET: 6.25% vs. IT: 6.22%; OR 1.03; 95% CI 0.62 to 1.69; P=0.91)
    • all-cause mortality (ET: 18.45% vs. IT: 17.35%; OR 1.00; 95% CI 0.73 to 1.39; P=0.99)

Full Text:  Lin. Efficacy and Safety of Endovascular Treatment versus Intravenous Thrombolysis for Acute Ischemic Stroke: A Meta-Analysis of Randomized Controlled Trials. PLoS ONE 2013;8(10):e77849


Observational Studies

Stroke:     Therapeutic Hypothermia

Hong and colleagues undertook a dual-centre, prospective cohort study in patients with acute anterior circulation ischemic stroke and an initial National Institutes of Health Stroke Scale ≥10 who had successful recanalization, comparing a mild hypothermia (34.5°C) protocol (centre A, n=39), including mechanical ventilation, 48-hour hypothermia and 48-hour rewarming, with standard therapy without cooling (centre B, n=36), and found:

  1. hypothermia was associated
    • with improvements in
      • cerebral edema (P=0.001)
      • hemorrhagic transformation (P=0.016)
      • good outcome (3-month modified Rankin Scale, ≤2) (P=0.017)
    • no improvements in
      • mortality
      • hemicraniectomy rate
      • medical complications
  2. After adjustment for potential confounders, independent predictors for good outcome were
    • therapeutic hypothermia (odds ratio 3.0; 95% CI 1.0–8.9; P=0.047)
    • distal occlusion (odds ratio 7.3; 95% CI 1.3–40.3; P=0.022) 
    • absence of cerebral edema (odds ratio 5.4; 95% CI 1.6–18.2; P=0.006)
    • no medical complications (odds ratio 9.3; 95% CI 2.2–39.9; P=0.003)

Abstract:  Hong. Therapeutic Hypothermia After Recanalization in Patients With Acute Ischemic Stroke. Stroke 2013;epublished November 7th


BMC Nephrology:     Chloride and AKI

Zghang and colleagues completed a single centre, retrospective study examining the association between plasma chloride concentration and renal function in 1,221 critically ill patients, and found:

  1. 357 patients (29.2%) developed AKI
  2. pre-AKI plasma chloride values were significantly higher in AKI than in non-AKI patients
    • maximum plasma chloride  (111.8 ± 8.1 vs 107.9 ±5.4 mmol/l; p < 0.001)
    • mean plasma chloride (104.3 ±5.8 vs 103.4 ± 4.5; p = 0.0047) 
  3. the initial chloride plasma level on admission to ICU was not significantly different between AKI and non-AKI patients
  4. in multivariable analysis, pre-AKI maximum plasma chloride was associated with the development of AKI (OR 1.10, 95% CI 1.08 to 1.13)

Full Text: Zhang. Higher serum chloride concentrations are associated with acute kidney injury in unselected critically ill patients. BMC Nephrology 2013;14:235


Intensive Care Medicine:     Bleeding Risk with Heparin

In an analysis of the international, multi-centre PROTECT study (n=3,746), Lauzier et al evaluated the predictors of major bleeding and the association between bleeding and mortality in medical–surgical critically ill patients receiving heparin thromboprophylaxis, and found:

  1. bleeding occurred in 5.6% (95% CI 4.9–6.3%)
  2. time-dependent predictors were
    • prolonged activated partial thromboplastin time (hazard ratio 1.10, 1.05–1.14 per 10 s increase)
    • lower platelet count (HR 1.16, 1.09–1.24 per 50 × 109/L decrease)
    • therapeutic heparin (HR 3.26, 1.72–6.17)
    • antiplatelet agents (HR 1.38, 1.02–1.88)
    • renal replacement therapy (HR 1.75, 1.20–2.56)
    • recent surgery (HR 1.64, 1.01–2.65)
  3. type of pharmacologic thromboprophylaxis was not associated with bleeding
  4. patients with bleeding had a higher risk of in-hospital death (HR 2.09, 1.69–2.57)

Abstract:  Lauzier. Risk factors and impact of major bleeding in critically ill patients receiving heparin thromboprophylaxis. Intensive Care Med 2013;39(12):2135-2143


Intensive Care Medicine:     Hydroxyethyl Starches

In a post hoc analysis of the 6S study (HES 130/0.42 versus Ringer’s acetate in 798 patients with severe sepsis), Haase and colleagues characterized bleeding in patients treated with hydroxyethyl starch, and found:

  1. HES was associated with an increased incidence of haemorrhage in the ICU
    • overall bleeding
      • 93 (23 %) versus 60 (15 %) patients
      • relative risk 1.55 (95 % CI 1.16 to 2.08; P = 0.003)
      • hazard ratio 1.70 (95 % CI 1.23 to 2.36; P = 0.001)
      • adjusted hazard ratios for death 1.36 (95 % CI 1.04 to 1.79; P = 0.03)
    • severe bleeding (intracranial or concomitant transfusion with three units of red blood cells)
      • 38 versus 25 patients
      • risk ratio 1.52; 95 % CI 0.94 to 2.48; P = 0.09)
      • hazard ratio 1.55 (95 % CI 0.93 to 2.56; P = 0.09)
      • adjusted hazard ratios for death 1.74 (95 % CI 1.20 to 2.53; P = 0.004)
  2. Most patients bled in the first days after randomization when most trial fluid was given

Abstract:  Haase. Bleeding and risk of death with hydroxyethyl starch in severe sepsis: post hoc analyses of a randomized clinical trial. Intensive Care Med 2013;39(12):2126-2134


Critical Care Medicine:     Septic Shock

Pavon et al completed a 3 month multi-centre observational cohort study (n=10.941), examining the mortality of ICU patients after an initial episode of septic shock, and found:

  1. incidence of septic shock was 13.7% (n=1,495)
  2. baseline characteristics
    • median age 68 years (range 58–78)
    • 84% of admissions were medical
    • Simplified Acute Physiological Score II of 56 (45–70) [Median (interquartile range)]
    • Sequential Organ Failure Assessment of 11 (9–14)
  3. mortality
    • ICU 39.4%
    • hospital 48.6%
    • 3 months 52.2%
  4. factors significantly associated with increased risk of death
    • older age
    • male sex
    • comorbidities (immune deficiency, cirrhosis)
    • Knaus C/D score
    • high Sequential Organ Failure Assessment score

Abstract:  Pavon. Profile of the Risk of Death After Septic Shock in the Present Era: An Epidemiologic Study. Critical Care Med 2013;41(11):2600-2609


Other Observational Studies of Interest

Journal of Antimicrobial Chemotherapy:     Vancomycin during CRRT

Abstract:  Beumier. A new regimen for continuous infusion of vancomycin during continuous renal replacement therapy. J Antimicrob Chemother 2013;68:2859-2865


Journal of Antimicrobial Chemotherapy:     Candidaemia

Abstract:  Kim. Clinical impact of time to positivity for Candida species on mortality in patients with candidaemia. J Antimicrob Chemother 2013;68:2890-2897


JAMA:     Testosterone

Full Text:  Vigen. Association of Testosterone Therapy With Mortality, Myocardial Infarction, and Stroke in Men With Low Testosterone Levels. JAMA 2013;310(17):1829


JAMA:     Night-Time Work & Surgical Safety

Abstract:  Vinden. Complications of Daytime Elective Laparoscopic Cholecystectomies Performed by Surgeons Who Operated the Night Before. JAMA 2013;310(17):1837


European Heart Journal: Acute Cardiovascular Care:     Myocardial Infarction

Full Text:  Puymirat. Euro Heart Survey 2009 Snapshot: regional variations in presentation and management of patients with AMI in 47 countries. European Heart Journal: Acute Cardiovascular Care 2013;2:359


JAMA Internal Medicine

Full Text:  Soliman. Atrial Fibrillation and the Risk of Myocardial Infarction. JAMA Intern Med 2013;epublished November 4th


Journal of the American Medical Association:     Acute Kidney Injury

Abstract: Gandhi. Calcium-Channel Blocker–Clarithromycin Drug Interactions and Acute Kidney Injury. JAMA 2013;epublished November 9th



Guideline & Position Statement


Saudi Journal of Anesthesia:     Impact Factor


American Journal of Critical Care:     Electronic Health Record



Neurology Today:     Delirium


Neurology Today:     Dead Donor Rule


Neurology Today:     Subarachnoid Haemorrhage


Nature Medicine:     Placebo Effect


JAMA:     Peer Revew


Emergency Medicine News:     Brain Death


Emergency Medicine News:     Oxygen Administration


Emergency Medicine News:     ET Tube Placement

Emergency Medicine News:     Decision Making

Review - Clinical



















World Journal of Critical Care Medicine:     Computerized Decision Support


New England Journal of Medicine:     Mass Disasters


International Journal of Inflammation:     RAGE


South Africian Journal of Anaesthesia and Analgesia:     Microgravity-Exposed Individuals


Heart, Lung and Vessels:     Perioperative Mortality


ICU Management:     Organ Donation


ICU Management:     French Critical Care


ICU Management:     Interview with Prof Gordon Rubenfeld


Review - Non-Clinical

New England Journal of Medicine:     Medicaid  


South Africian Journal of Anaesthesia and Analgesia:     Research Consent


I hope you find these brief summaries and links useful.

Until next week


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