Newsletter 127 / May 11th 2014




Welcome to the 127th 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, guidelines, commentaries and editorials from hundreds of clinical and scientific journals.

This week's research studies include randomized controlled trials on IV iron supplementation, intermittent sedation, Clostridium difficile therapy and eplerenone in acute STEMI; one meta analysis addresses the significance of echocardiographic right ventricular dysfunction in PE; observational studies focus on  use of analgesics, sedatives and neuromuscular blockade in Canada, and glutamine (in a post hoc analysis of REDOXS). Additional studies include a study related to FEAST, this time investigating red cell transfusion in anaemic Ugandan children, as well as studies on fluconazole prophylaxis in premature infants, lung ultrasound for fluid loading, causes of death in the USA, perioperative mortality in the UK, perioperative TRALI, cardivascular events post acute kidney injury, lactate measurement post cardiac arrest and the development of a new perioperative geriatric fraility score

This month's Cochrane reviews include new reviews on hypoxaemia in mechanical ventilation and subsegmental PE therapy, as well as updated reviews on digoxin therpy for heart failure and fluid therapy in bacterial meningitis.

There are a number of guidelines this week, on the correct measurement of cerebral perfusion pressure (ht @elfyn_thomas), surgical site infection, C. diff infection and hypertension. Commentaries focus on ebola, ultrasound for pneumothorax and transcatheter aortic valve replacement plus pragmatic clinical trials, and there are four interesting case reports.

Amongst the clinical review articles are papers on status epilepticus, mechanical circulatory support, several on myocarditis, ECMO, negative pressure pulmonary oedema, cardiac dysfunction post liver transplantation, uncontrolled sepsis, traumatic haemorrhagic shock, and bioterrorism. Non-clinical reviews discuss social media in education, perioperative physician performance feedback, clinical trials and clinical inertia. 

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

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Randomized Controlled Trial

Pieracci and colleagues compared iron sucrose 100 mg IV with placebo thrice weekly for up to 2 weeks in 150 critically ill trauma patients with anaemia (Hb < 12 g/dL), and found:

  1. at baseline, patient profiles were consistent with functional iron deficiency
    • 89.3% were hypoferremic
    • 34.0% were hyperferritinemic
    • 42.7% had iron-deficient erythropoiesis
    • transferrin saturation was 8% (range, 2-58%)
  2. in the subgroup (n=57) of patients who received all six doses of study drug 
    • iron supplementation was associated with increased serum ferritin concentrations
      • day 7 (808.0 ng/mL vs 457.0 ng/mL, p < 0.01)
      • day 14 (1,046.0 ng/mL vs 551.5 ng/mL, p < 0.01)
  3. there was no significant difference between groups in
    • transferrin saturation
    • erythrocyte zinc protoporphyrin concentration
    • hemoglobin concentration
    • packed RBC transfusion requirement
    • risk of infection
    • length of stay
    • mortality

Abstract:  Pieracci. A Multicenter, Randomized Clinical Trial of IV Iron Supplementation for Anemia of Traumatic Critical Illness. Critical Care Med 2014;epublished May 2nd

Junior and colleagues compared interruption of continuous daily sedation with intermittent sedation in 60 patients critically ill patients expected to need mechanical ventilation for more than 24 hours, in a low nurse staffing ICU, and found:

  1. no differences in
    • ventilator-free days at day 28   (interruption group 24 days vs intermittent group 25 days, P = 0.160)
    • ICU mortality (40 versus 23.3%, P = 0.165)
    • hospital mortality (43.3 versus 30%, P = 0.284)
    • incidence of delirium (30 versus 40%, P = 0.472)
    • self-extubation (3.3 versus 6.7%, P = 0.514)
    • psychological stress six months after ICU discharge
    • nurse workload
  2. interruption of daily sedation was associated with
    • increased total doses of fentanyl and midazolam
  3. intermittent sedation was associated with
    • higher tidal volumes

Full Text:  Junior. Daily sedative interruption versus intermittent sedation in mechanically ventilated critically ill patients: a randomized trial. Annals of Intensive Care 2014;4:14

Johnson and colleagues completed two multinational trials, comparing oral tolevamer (n=563; 9g loading dose, followed by 3 g 8 hourly for 14 days), vancomycin (n=266; 125 mg 6 hourly for 10 days), or metronidazole  (n=289; 375 mg 6 hourly for 10 days) in a 2:1:1 ratio, and found:

  1. in a pooled analysis,
    • clinical success of each drug was
      • tolevamer (44.2%)
      • metronidazole (72.7%)
      • vancomycin (81.1%) 
    • tolevamer was inferior to both metronidazole and vancomycin (P<0.001)
    • metronidazole was inferior to vancomycin (P=0.02)
  2. for patients with severe Clostridium difficile infection
    • metronidazole trended towards being inferior to vancomycin (66.3% vs 78.5%; p=0.059)
  3. no difference in adverse events

Abstract:  Johnson. Vancomycin, Metronidazole, or Tolevamer for Clostridium difficile Infection: Results from Two Multinational, Randomized, Controlled Trials.  Clin Infect Dis 2014;epublished May 5th

Montalescot and colleagues compared eplerenone (25–50 mg once daily) with placebo in 1,012 patients with acute STEMI without heart failure, and found:

  1. eplerenone was associated with
    • reduction in the composite primary outcome
      • 18.2% vs 29.4%; adjusted hazard ratio 0.58; 95% CI 0.45 to 0.76; P < 0.0001
    • the primary endpoint was driven by a high BNP/NT-proBNP level
      • adjusted HR 0.60; 95% CI 0.45 to 0.79; P < 0.0003
    • reduced incidence of hypokalaemia (< 3.5 mmol/L)
      • 1.4 vs. 5.6% (P = 0.0002)
    • a trend towards increased incidence of hyperkalaemia (> 5.5 mmol/L)
      • 5.6 vs. 3.2% (P = 0.09)
  2. no difference in adverse events

Abstract:  Montalescot. Early eplerenone treatment in patients with acute ST-elevation myocardial infarction without heart failure: The Randomized Double-Blind Reminder Study. Eur Heart J 2014;epublished April 29th

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Meta Analysis

Cho et al pooled data from 12 studies investigating right ventricular dysfunction (RVD) on echocardiography in 3,283 hemodynamically stable patients with acute PE, and found:

  1. 37.3% (n=1,223) had RVD
  2. 62.7% (n=2,060) had normal right ventricular function
  3. short-term mortality was reported in
    • 13.7% (167/1223) of patients with RVD
    • 6.5% (134/2060) of patients without RVD
  4. RVD on echocardiogram was associated with a
    • increased in short-term mortality
      • odds ratio 2.29, 95% CI 1.61 to 3.26

Full Text:  Cho. Right ventricular dysfunction as an echocardiographic prognostic factor in hemodynamically stable patients with acute pulmonary embolism: a meta-analysis. BMC Cardiovascular Disorders 2014;14:64

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Observational Studies

Burry and colleagues performed a two week observational study (n=712, 3,620 patient days) in 51 Canadian ICUs aiming to describe analgo-sedation, antipsychotic and neuromuscular blocking drug use, and found:

  1. regarding mechanical ventilation
    • median duration 3.0 days (IQR 2 to 6)
    • during mechanical ventilation
      • 92% received analgo-sedation,
      • 32% received adjunct agent (e.g., acetaminophen),
      • 18% received neuromuscular blockers
      • 10% received antipsychotics
  2. opioids were used more frequently than (P < 0.0001)
    • benzodiazepines (84.8% vs 62.2)
    • propofol (84.8%vs 10.1%)
  3. independent predictors of opioid and benzodiazepine use were
    • longer MV duration
    • assessment scales
    • physical restraints
    • university-affiliated hospital
  4. the use of scales, protocols etc were
    1. sedation scale 53.0%,
    2. pain scale 19.1%,
    3. delirium scale 5.2%,
    4. protocol 25.0%,
    5. daily sedation interruption 42.1%

Abstract:  Burry. Analgesic, sedative, antipsychotic, and neuromuscular blocker use in Canadian intensive care units: a prospective, multicentre, observational study. Can J Anaesth 2014;epublished May 1st

Heyland and colleagues performed a post hoc analysis of the REDOXS study (1,223 critically ill mechanically ventilated patients with multiorgan failure randomized to receive glutamine, antioxidants, both glutamine and antioxidants, or placebo) aiming to reevaluate the effect of supplementation after controlling for baseline covariates and to identify potentially important subgroup effects, and found:

  1. the 28-day mortality rates were
    • placebo 25%
    • glutamine 32%
    • antioxidant 29%
    • combination 33%
  2. adjusted odds ratio of 28-day mortality vs placebo
    • glutamine 1.5 (95% CI 1.0 to 2.1, P = 0.05)
    • antioxidants 1.2 (95% CI 0.8 to 1.8, P = 0.40)
    • glutamine & antioxidants 1.4 (0.9 to 2.0, P = 0.09) 
  3. in subgroup analysis
    • both glutamine and antioxidants appeared most harmful in patients with baseline renal dysfunction.
  4. no subgroups suggested reduced mortality with supplements

Abstract:  Heyland. Glutamine and Antioxidants in the Critically Ill Patient. A Post Hoc Analysis of a Large-Scale Randomized Trial.  JPEN J Parenter Enteral Nutr 2014;epublished May 5th

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Additional Studies

Randomized Controlled Trials

Observational Studies

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Cochrane Reviews



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Guidlines and Position Statements


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Clinical Review Articles











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Non-Clinical Review Articles

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I hope you find these brief summaries and links useful.

Until next week