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Newsletter 139 / August 3rd 2014



Welcome to the 139th 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.

In news this week, the ebola outbreak in West Africa continues to spread. This week's research studies include randomized controlled trials on steroid therapy for the prevention of hospital-acquired pneumonia in traumatic brin injury, distributive septc shock therapy, and microcirculation-directed therapy; meta analyses on adrenaline use for out-of-hospital cardiac arrest, perioperative β blockade and thoracic epidural analgesia for general surgery, and open lung biopsy in ARDS; plus observational studies on  adrenal insufficiency, steroid therapy for septic shock, appropriate antimicrobial therapy, and mortality from severe sepsis. There are 8 additional studies including investigations on a simplified severe sepsis protocol and thoracic trauma.

This month's new Cochrane reviews address sedation interruption, mannitol vs hypertonic saline for ICP control, physician anaesthetists, antibody therapy post liver transplantation, and thoracic epidural technique, whilst updated reviews look at peritoneal dialysis, endovascular therapy for ruptured abdominal aortic aneurysm and stroke thrombolysis. This week's guidelines include papers from both Europe and America on perioperative cardiovascular evaluation and management for non-cardiac surgery, as well as guidance on management of stable ischaemic heart disease. There are editorials on routine preoxygenation, malaria therapy and education in anaesthesia; commentaries on defensive medicine and education, plus case reports on prolonged CPR, haemodialysis catheter insertion, cardiac trauma and cerebral salt wasting syndrome.

Amongst the clinical review articles are papers on neurological monitoring, pacemakers, perioperative β blockade, airway anatomy for bronchoscopy, interruptions to enteral nutrition, acute kidney injury, melatonin, sepsis-associated liver dysfunction, MERS, acute compartment syndrome, and postpartum infective endocarditis. There is a single basic science review article on the physics and equipment of ultrasound. The beginning of each month marks the addition of recently made open access articles from the major critical care journals, with papers from the American Journal of Respiratory and Critical Care Medicine, Chest, Critical Care, Anesthesiology and Anesthesia & Analgesia. Continuing our focus on excellent open access critical care journals, the This Week's Papers is a selection of papers from the the International Journal of Critical Illness and Injury Science, starting with a paper on videolaryngoscopy in tomorrow's Paper of the Day.

Unfortunately, as the British Medical Journal has returned its excellent statistics series, containing over 200 articles, behind its paywall, I have taken these popular links down from the site. Critical Care Reviews promotes open access to scientific advancement and doesn't feature subscription requiring material, apart from major research findings.

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Upcoming Meetings

Critical Care Reviews Meeting 2015

The 2015 Critical Care Reviews Meeting, being held in association with the Northern Ireland Intensive Care Society, is on Friday January 23rd, at the Galgorm Resort and Spa, outside Belfast, Northern Ireland. Further details will follow over the next couple of months, with registration opening the first week in October. The impressive list of speakers includes Clifford Deutschman (USA), the immediate past president of the Society of Critical Care Medicine, Niklas Nielsen (Sweden), Eddy Fan (Canada), Kathy Rowan (England), Danny McAuley, Eamon McCoy, and John Hinds (Northern Ireland), plus a host of local intensivists. The theme of the meeting is to discuss the biggest research findings of the past year, with the aim of deciding whether you should implement these results into your current practice.

SMACC Chicago

The next SMACC conference will be held June 23rd to 26th, in Chicago, USA. Just like the Critical Care Reviews Meeting, this is a not-for-profit event, run by a team interested in sharing knowledge in a fun, modern way. It's a conference like no other. Further details will be out soon on the SMACC website.

Intensive Care Society State-of-the-Art Meeting

The 2014 ICS State-of-the-Art Meeting is on December 8th to 10th at the Excel Arena in London. The speakers have been announced, with further details available from the ICS website.

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Critical Care Horizons

Critical Care Horizons is a fresh new voice in the critical care literature, offering thought-provoking, cutting-edge commentary and opinion papers, plus state-of-the-art review articles. The journal is free to publish with and free to read, opening authorship opportunity to all. The energetic editorial board consists of a deliberate mix of clinicians active in social media and world renowned academics, all driven by a desire to improve the care we offer our patients, and operate without financial gain or incentive. A call for papers has been issued, so if you have something interesting to say, and can say it in an engaging manner, please get in touch. The first issue will be released on January 1st 2015. We also need peer reviewers - if you would like to contribute to this altruistic initiative, please register on the site.

COI - I am the editor-in-chief of this new journal, but work in a voluntary capacity, as do all the editors.

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Randomized Controlled Trials

Asehnoune and colleagues completed a phase 3, stratified, blinded, randomized controlled trial in 19 French ICUs, comparing combined steroid therapy (n=168; hydrocortisone 200 mg per day tapered plus fludrocortisone 50 μg per day) with matching placebo (n=168) for 10 days, on the development of hospital-acquired pneumonia, in 336 adults aged 15 to 65 years within 24 hours of suffering a severe traumatic brain injury. Adrenal function was investigated with a short corticotropin test prior to drug administration, which was stopped if adrenal insufficiency was absent. The authors found:

  1. 8 patients withdrew consent
  2. combined hydrocortisone / fludrocortisone therapy was associated with
    • no statistically significant difference in
      • intention-to-treat analysis
        • development of hospital-acquired pneumonia at day 28 (1° outcome)
          • steroid group 45% (74/165) vs placebo 53% (87/163); HR 0·75, 95% CI 0·55 to 1·03, p=0·07
          • steroid group 86 episodes HAP vs placebo group 110 episodes HAP 
            • (median 0, IQR 0—1 vs median 1, IQR 0—1 cases per patient, p=0·07)
      • modified intention-to-treat analysis, steroids versus placebo
        • in patients with adrenal insufficiency
          • HR 0·80 (95% CI 0·56 to 1·14, p=0·22)
        • in patients with normal adrenal function
          • HR 0·48 (0·23 to 1·01; p=0·05)
  3. there were no adverse events related to treatment
  4. the study was underpowered due to a lower than expected incidence of hospital-acquired pneumonia in the placebo group

Abstract: Asehnoune. Hydrocortisone and fludrocortisone for prevention of hospital-acquired pneumonia in patients with severe traumatic brain injury (Corti-TC): a double-blind, multicentre phase 3, randomised placebo-controlled trial. Lancet Respiratory Medicine 2014;epublished July 24th

Vincent and colleagues performed an international, open-label, multicentre, randomized, placebo controlled trial in 337 patients with distributive septic shock receiving vasopressor therapy, comparing the hemoglobin-based nitric oxide scavenger pyridoxalated hemoglobin polyoxyethylene (n=183; 0.25 mL/kg/hr; 20 mg Hb/kg/hr) with an equal volume of placebo (n=194), infused for up to 150 hours, and found:

  1. the groups were similar at baseline
  2. the study was stopped after an interim analysis showed
    • in the pyridoxalated hemoglobin polyoxyethylene group
      • a non-statistically significant higher 28 day mortality
        • 44.3% vs 37.6%; OR 1.29, 95% CI 0.85 to 1.95; p = 0.227
      • in patients with higher organ dysfunction scores (SOFA score > 13)
        • a statistically significant higher 28 day mortality
          • 60.9% vs 39.2%; p = 0.014
      • an increased prevalence of adverse events
      • survivors had a longer vasopressor-free time (21.3 vs 19.7 d; p = 0.035)

Abstract:  Vincent. Multicenter, Randomized, Placebo-Controlled Phase III Study of Pyridoxalated Hemoglobin Polyoxyethylene in Distributive Shock (PHOENIX). Critical Care Med 2014;epublished July 31st

Trzeciak and colleagues undertook a single-centre, randomized, sham-controlled clinical trial in 50 patients with septic shock, comparing the effects on the microcirculation of 6 hours of inhaled nitric oxide (n=40 ppm) or sham inhaled nitric oxide on the microculation, administered after achievement of macrocirculatory resuscitation, and found:

  1. of the 50 patients
    • 56% (28/50) required vasopressors
    • 30% (15/50) died
  2. inhaled nitric oxide was associated with
    • statistically significantly higher
      • plasma nitrite levels
    • no statistically significant improvement in
      • microcirculatory flow
      • lactate clearance
      • organ dysfunction

Abstract:  Trzeciak. Randomized Controlled Trial of Inhaled Nitric Oxide for the Treatment of Microcirculatory Dysfunction in Patients With Sepsis. Crit Care Med 2014;epublished July 30th

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Meta Analyses

Atiksawedparit et al pooled data from 13 observational studies (n ranging from 2,381 to 421,459), examining the effects of prehospital adrenaline administration on out-of-hospital cardiac arrest outcomes, and found:

  1. prehospital adrenaline administration was associated with:
    • increased prehospital return of spontaneous circulation
      • RR 2.89; 95% CI 2.36 to 3.54
    • no statistically significant effects on
      • overall return of spontaneous circulation
        • RR 0.93, 95% CI 0.5 to 1.74
      • admission
        • RR 1.05, 95% CI 0.80 to 1.38
      • survival to discharge
        • RR 0.69, 95% CI 0.48 to 1.00

Full TextAtiksawedparit. Effects of prehospital adrenaline administration on out-of-hospital cardiac arrest outcomes: a systematic review and meta-analysis. Critical Care 2014; 18:463

Wijeysundera evaluated 17 studies {16 RCTs (n=12,043), 1 cohort study (n=348)}, investigating whether initiation of β blockade within 45 days prior to noncardiac surgery reduces 30-day cardiovascular morbidity and mortality, and found:

  1. in the RCTS
    • β blockade
      • decreased
        • nonfatal myocardial infarction 
          • RR 0.69; 95% CI 0.58 to 0.82
      • increased
        • nonfatal stroke
          • RR 1.76; 95% CI 1.07 to 2.91
        • hypotension
          • RR 1.47; 95% CI 1.34 to 1.60
        • bradycardia
          • RR: 2.61; 95% CI 2.18 to 3.12
      • these findings were qualitatively unchanged after exclusion of the DECREASE and POISE-1 trials
  2. the effect of β blockade on
    • all-cause mortality was:
      • uneffected in the DECREASE trials (RR: 0.42; 95% CI: 0.15 to 1.22)
      • increased in other trials (RR: 1.30; 95% CI: 1.03 to 1.64)
    • cardiovascular mortality
      • decreased in the DECREASE trials (RR:0.17; 95% CI: 0.05 to 0.64)
      • uneffected in other trials (RR: 1.25; 95% CI: 0.92 to 1.71)
    • these differences were qualitatively unchanged after the POISE-1 trial was excluded

Full Text:  Wijeysundera. Perioperative Beta Blockade in Noncardiac Surgery: A Systematic Review for the 2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014;epublished August 1st

Shi et al pooled 12 randomized controlled trials (n=650) comparing thoracic epidural analgesia (n=331) with systemic analgesia (n=319) on the recovery of gastrointestinal function in patients following GI surgery, and found:
  1. thoracic epidural analgesia was associated with:
    • shorter time to
      • first passage of flatus by 31.3 h, 95% CI −33.2 to −29.4, P < 0.01
      • first passage of stool by 24.1 h, 95% CI −27.2 to −20.9, P  < 0.001
    • higher postoperative hypotension, RR 7.9, 95% CI 2.4 to 26.5, P = 0.001
    • no difference between the groups in the incidence of
      • anastomotic leakage
      • ileus
      • other side effects
        • pruritus
        • vomiting

Abstract:  Shi. Recovery of gastrointestinal function with thoracic epidural vs. systemic analgesia following gastrointestinal surgery. Acta Anaesthesiologica Scandinavica 2014;epublished July 24th

Libby et al reviewed 24 articles examining the utility of open lung biopsy in ARDS, and found the procedure:

  1. provided a specific diagnosis in 84% of patients
  2. altered management in 73%
  3. hospital mortality was 43%
  4. the complication rate was 22%
  5. death from OLB was rare

Abstract:  Libby. Surgical Lung Biopsy in Adult Respiratory Distress Syndrome: A Meta-Analysis. Ann Thorac Surg 2014;epublished July 25th

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Observational Studies

Boonen and colleagues harvested adrenal glands within 24 hours of death from 13 long-stay ICU patients, 27 short-stay ICU patients and 13 controls, evaluating whether longer duration of critical illness was associated with subnormal ACTH adrenocortical stimulation, predisposing to adrenal insufficiency, and found:

Abstract:  Boonen. Impact of duration of critical illness on the adrenal glands of human intensive care patients. Journal of Clinical Endocrinology & Metabolism 2014;epublished July 25th

Funk et al completed an international, retrospective, multicenter, propensity-matched cohort study from 1996 to 2007, in 6,663 patients with septic shock, of whom 1,838 received IV low-dose corticosteroid treatment within 48 hours of the diagnosis of septic shock and were matched to a comparable group who did not receive low-dose corticosteroid, and found:

  1. corticosteroid therapy was associated with
    • no statistically significant improvement in 30-day mortality 
      • 35.5% vs 34.9%; HR 0.98; 95% CI 0.88 to 1.10; p = 0.77
    • lower 30 day mortality
      • in the subgroup of patients with the APACHE II score quartile ≥30
        • 50.6% vs 55.8%; HR 0.81; 95% CI 0.68 to 0.97; p = 0.02
    • corticosteroid therapy was not associated with
      • reductions in ICU (30.3% vs 30.4%; OR 0.99; 95% CI 0.86 to 1.15; p = 0.94)
      • hospital mortality (43.4% vs 42.1%; odds ratio 1.05; 95% CI 0.93 to 1.20; p = 0.42)
      • ventilator-free days (medians 13  vs 15; p = 0.8)
      • pressor/inotrope-free days (medians 25 vs 24; p = 0.63

Abstract:  Funk. Low-Dose Corticosteroid Treatment in Septic Shock: A Propensity-Matching Study.Crit Care Med 2014;epublished July 28th

Vazquez-Guillamet and colleagues performed a retrospective, single-centre, cohort study examining the appropriateness of antimicrobial therapy as an outcome determinant in 2,594 patients with severe sepsis and septic shock using the number needed to treat, and found:
  1. overall mortality rate was 30.3%
  2. inappropriate antimicrobial treatment had the greatest adjusted odds ratio for hospital mortality
    • aOR 3.4; 95% CI 2.8 to 4.1; p < 0.001
  3. inappropriate antimicrobial treatment was associated with
    • resistance to
      • cefepime
      • meropenem
    • presence of multidrug resistance
    • nonabdominal surgery
    • prior antibiotic use 
  4. the number needed to treat with appropriate antimicrobial therapy to prevent one patient death was 4.0 (95% CI 3.7 to 4.3)
  5. the prevalence-adjusted pathogen-specific number needed to treat (PNNT) with appropriate antimicrobial therapy to prevent one patient death was
    • multidrug-resistant bacteria (PNNT = 20)
    • Candida species (PNNT = 34)
    • methicillin-resistant Staphylococcus aureus (PNNT = 38)
    • Pseudomonas aeruginosa (PNNT = 38)
    • Escherichia coli (PNNT = 40)
    • methicillin-susceptible S. aureus (PNNT = 47)

Abstract:  Vazquez-Guillamet. Using the Number Needed to Treat to Assess Appropriate Antimicrobial Therapy as a Determinant of Outcome in Severe Sepsis and Septic Shock. Crit Care Med 2014;epublished July 28th

Linder and colleagues completed a single centre, prospective cohort study in 2,289 patients comparing the 1- to 10-year mortality rates of previously healthy patients with severe sepsis with patients with nonseptic critical illness and the local general population using life tables, and found:

  1. patients with severe sepsis without comorbidities
    • compared with the general population
      • overall had higher mortality from 1 to 10 years
        • 1- to 5-year mortality: HR 4.5, 95% CI 2.2 to 9.1
        • 5- to 10-year mortality: HR 2.2, 95% CI 0.9 to 14.7
      •  younger patients (< 60 yr) with severe sepsis
        • had higher mortality from 1 to 10 years
          • 1- to 5-year mortality (HR 17.8, 95% CI 13.4 to 24.8)
          • 5- to 10-year mortality (HR 6.0, 95% CI 4 to 9)
    • compared with patients with nonseptic critical illness
      • had higher 1- to 10-year mortality rates (30.5% vs 22.1%)
    • compared with patients who have undergone cardiovascular surgery
      • had higher 1- to 10-year mortality rates (30.5% vs 15.9%)

Abstract:  Linder. Long-Term (10-Year) Mortality of Younger Previously Healthy Patients With Severe Sepsis/Septic Shock Is Worse Than That of Patients With Nonseptic Critical Illness and of General Population. Critical Care Med 2014;epublished July 22nd

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Additional Studies

Randomized Controlled Trial

Meta Analysis

Observational Studies

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Cochrane Reviews



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Guidelines & Positional Statements

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Case Reports


Clinical Review Articles











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Recently Made Open Access Articles from the Major Journals

American Journal of Respiratory & Critical Care Medicine

Review Articles



Review Articles

Case Reports

Critical Care

Review Articles



Anesthesia & Analgesia

Review Articles

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Basic Science Review Articles

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I hope you find these brief summaries and links useful.

Until next week