Newsletter 108 / December 29th 2013

Happy New Year



Welcome to the 108th 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, editorials, commentaries and more from over 300 clinical and scientific journals.

This week there are a number of randomized controlled trials, including investigations into fluids for burns resuscitation, decontamination, alcohol withdrawal, severe sepsis, family presence during brain death testing and hyperproteic feeding. Meta analyses examine prone position ventilation, organ dysfunction post severe sepsis and the relationship between cervical collar use and pressure ulcers. Observational studies focus on the use of diaphragmatic ultrasound to predict extubation success, again prone positioning and pressure ulcers, statins in sepsis, age in emergency thoracotomy, tranexamic acid and seizures, pneumococcal pneumonia, SSRI use and subsequent mortality, polymyxin B haemoperfusion and sepsis biomarker startification.

This week's guidelines look at damage control surgery, circulatory genetics and stroke mortality. A single study critique reviews the recent Mathurin paper on combined pentoxifylline and prednisolone for alcoholic hepatitis.

Editorials address stroke neuroprotection and the ageing, tiring, ailing anaesthetist, while commentaries focus on open access journals, acute renal failure and patience with patients.

Amongst the clinical review articles are papers on stroke, levosimendan, fluid responsiveness, pulmonary embolism, critical care nutrition, non-alcoholic fatty liver disease, urinary tract infection, acute kidney injury, diabetes, new oral anticoagulants, surviving sepsis campaign and paracetamol toxicity, while non-clinical reviews discuss social media for physicians.

There are four statistics papers in the basic science review articles section, including papers on meta analysis and modern statistical methods.

The topic for This Week's Papers is critical care complications of haematological malignancies, starting with a paper on tumour lysis syndrome in tomorrow's Paper of the Day.

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Critical Care Reviews Meeting

It's just 3 weeks to the 2014 Critical Care Reviews Meeting. This year we discuss the major studies from the past 12 months, hear from our international guest speakers, Prof Alistair Nichol (Dublin/Melbourne), Prof Mervyn Singer (London) and Prof John Marshall (Toronto), and have updates on ICU infections, massive haemorrhage and acute liver failure. The evening session provides an opportunity to chat with our guest speakers in a novel, informal setting - beside a blazing log fire in a beautiful lounge - perfect for a cold winters night. This will be followed by dinner and the chance to meet new colleagues and friends.

If you're a drive or short flight away, it would be great to have you come along. Travel on Thursday, attend the meeting on Friday and see some of the local landmarks over the weekend, before returning home on Sunday evening after a great winter break. On Saturday visit the North Coast: the World Heritage site Giants Causeway, Carrick-a-Rede rope bridge, Dunluce Castle and Bushmills Distillary, the oldest distillary in the world; while on Sunday experience Belfast: the new acclaimed Titanic Centre followed by a famous black taxi tour describing the troubled past of one of Europe's now most vibrant cities. The Galgorm Resort and Spa is one of Northern Ireland's premier hotels and is a 30 minute drive from Belfast International Airport. Special room rates are available, by quoting the meeting. Please feel free to contact me if you're thinking about making the trip - it would be great to hear from you.

This year, the meeting will be run in association with the Northern Ireland Intensive Care Society. Further details, the meeting programme, and registration can be accessed via these links.



Randomized Controlled Trials

Béchir and colleagues completed a randomized, controlled, double-blind trial in 48 patients with severe burns, comparing Lactated Ringer's solution plus 6% HES 130/0.4 in a ratio of 2:1, or Lactated Ringer's solution with no colloid supplement, for the first 72 hours, and found:
  1. no difference in
    • median volume of fluid administered at 3 days 
      • HES group: 19,535 ml
      • Lactated Ringer's group: 21,190 ml
      • (HES: -1,213 ml; P = 0.39)
    • creatinine levels day 1 to 3
      • (HES: +0.4 mumol/l; 95% CI -18.7 to 19.5; P = 0.97)
    • urinary output day 1 to 3
      • (HES: -58 ml; 95% CI -400 to 284; P = 0.90)
    • incidence of ARDS
      • (risk ratio 0.96; 95% CI 0.35 to 2.64; P = 0.95)(n=6 each group)
    • ICU length of stay
      • (HES vs. Lactated Ringer's: 28 vs. 24 days; P = 0.80) 
    • hospital length of stay
      • (31 vs. 29 days; P = 0.57)
    • 28-day mortality (n=4 each group)
      • (risk ratio 0.96; 95% CI 0.27 to 4.45; P = 0.95)(n=4 each group)
    • in-hospital mortality
      • ( HES n=8 vs. Lactated Ringer's n=5; hazard ratio 1.86; 95% CI 0.56 to 6.19; P = 0.31)
Camus et al performed a single centre, non-randomized, interrupted times series study, comparing the year before (n=925), with the year after (n=1,022), the implementation of a decontamination regimen of polymyxin/tobramycin/amphotericin B plus mupirocin/chlorhexidine in mechanically ventilated patients, and found:
  1. the intervention was associated with reductions in
    • infection rates  (5.3% vs 11.0%; p < 0.001)
    • incidence rates of total acquired infections (9.4 vs 23.6 per 1,000 patient-days; p < 0.001)
    • intubation-related pneumonia (5.1 vs 17.1 per 1,000 ventilator-days; p < 0.001) 
    • catheter-related bloodstream infections (1.0 vs 3.5 per 1,000 catheter-days; p = 0.03)
    • acquired infections
      • ceftazidime-resistant Enterobacteriaceae (0.8 ‰ vs 3.6 ‰; p < 0.001)
      • ciprofloxacin-resistant Enterobacteriaceae (0.8 ‰ vs 2.5 ‰; p = 0.02)
      • ciprofloxacin-resistant Pseudomonas aeruginosa (0.5 ‰ vs 1.6 ‰; p = 0.05)
      • colistin-resistant Gram-negative bacilli (0.7 ‰ vs 1.9 ‰; p = 0.04)
      • multidrug-resistant aerobic Gram-negative bacilli (p = 0.008)

Mueller and colleagues undertook a prospective, single centre, randomized, double-blind, placebo-controlled trial in 24 patients undergoing severe alcohol withdrawal, comparing lorazepam plus either of dexmedetomidine 1.2 µg/kg/hr (high dose), 0.4 µg/kg/hr (low dose), or placebo as adjunctive therapy for up to 5 days or resolution of withdrawal symptoms, and found:

  1. dexmedetomidine (combined groups) was associated with
    • reduced
      • 24-hour lorazepam requirement after versus before study drug (-56 mg vs -8 mg, p = 0.037)
        • median differences were similar for high dose and low dose dexmedetomidine therapy
    • increased
      • study drug adjustments (50% vs 0%, p = 0.02)
    • no difference in
      • cumulative 7-day lorazepam requirements (dexmedetomidine 159 mg versus placebo 181 mg)
      • rates of agitation within 24 hours of therapy onset
        • severe (dexmedetomidine 13% vs placebo 25%)
        • moderate (dexmedetomidine 27% vs placebo 22%) 
      • incidence of bradycardia  (25% vs 0%, not significant)
        • the majority of bradycardia occurred with high-dose dexmedetomidine (37.5%)
      • endotracheal intubation (n=0 both groups)
      • seizure (n=0 both groups)

Bernard et al completed an international, multi-centre, randomized (1:1:1), double-blind, placebo-controlled phase IIb trial, evaluating AZD9773 (a polyclonal antibody to tumor necrosis factor α) in 300 adults with severe sepsis/septic shock.  Patients received a single loading infusion of AZD9773 250 U/kg followed by 50 U/kg every 12 hours (low dose, n = 100), a single loading infusion of AZD9773 500 U/kg followed by 100 U/kg every 12 hours (high dose, n = 100), or placebo (n = 100) for 5 days. The authors found: 

  1. no difference in
    • mean number of ventilator-free days (primary endpoint)
      • low-dose AZD9773:  19.7 days (one-sided p = 0.18
      • high-dose AZD9773: 17.3 days (one-sided p = 0.74)
      • placebo: 18.3 days 
    • relative risk of death versus placebo at day 29
      • low-dose AZD9773: 0.80 (one-sided p = 0.25)
      • high-dose AZD9773: 1.64 (one sided p = 0.97)
    • incidence of adverse events or laboratory or vital sign abnormalities 

Tawil and colleagues perfromed a single centre, randomized controlled trial investigating whether family presence (n=58) during brain death testing improves understanding of brain death without affecting psychological distress, and found:

  1. 38 family members were present for 11 brain death evaluations and 20 family members were absent for six brain death evaluations
  2. baseline understanding scores were similar between groups  (p = 0.482)
    • present group: median 3.0 vs absent group: median 2.5
  3. presence during brain death testing was associated with
    • increased
      • understanding (p < 0.001)
        • median increase of 2 (IQR 1-2) versus 0 (IQR 0-0)
      • perfect "understanding scores" (p = 0.02)
        • 66% versus 20%
    • no effect on psychological well-being at follow up
      • Impact of Event Scale (p = 0.211)
        • present 20.5 versus absent 23.5
      • General Health Questionnaire (p = 0.250)
        • present 13.5 versus absent 13.0

Rugeles and colleagues undertook a blinded, randomized controlled trial in 80 critically ill adults comparing hyperproteic hypocaloric enteral nutrition (15 kcal/kg with 1.7 g/kg of protein) with isocaloric enteral nutrition (25 kcal/kg with 20% of the calories as protein), and found:

  1. no differences in
    • SOFA score at baseline
      • (7.5 (SD 2.9) vs 6.7 (SD 2.5) P = 0.17)
    • total amount of calories delivered
      • hyperproteic regimen 12 kcal/kg vs 14 kcal/kg in controls
  2. the hyperproteic regimen was associated with
    • increased protein delivery
      • (1.4 vs 0.76 g/kg, respectively P ≤ 0.0001)
    • improved 48 hour SOFA score
      • (delta SOFA 1.7 (SD 1.9) vs 0.7 (SD 2.8) P = 0.04)
    • less hyperglycemic episodes per day
      • (1.0 (SD 1.3) vs 1.7 (SD 2.5) P = 0.017)
    • trends towards reductions in
      • duration of mechanical ventilation days 
      • duration of ICU stay.

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 Meta Analysis

Lee and colleagues pooled data from 11 randomized controlled trials (n=2,246, n=1,142 prone) comparing mortality of prone-versus-supine positioning in patients with acute respiratory distress syndrome, and found prone positioning during ventilation was associated with:
  1. significant reductions in
    • overall mortality
      • (odds ratio 0.77; 95% CI 0.59 to 0.99; p = 0.039; I2 = 33.7%)
    • especially when prone positioning was more than 10 hr/session, compared with < 10 hours per day
      • (odds ratio 0.62; 95% CI 0.48 to 0.79; p = 0.039; p interaction = 0.015)
  2. significant increases in incidence of
    • pressure ulcers
      • (odds ratio 1.49; 95% CI 1.18 to 1.89; p = 0.001; I2 = 0.0%)
    • major airway problems
      • (odds ratio 1.55; 95% CI 1.10-2.17; p = 0.012; I2 = 32.7%)

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 Observational Studies

Di Nino and colleagues examined whether ultrasound derived measures of diaphragm thickening {percent change in diaphragm thickening (tdi) between end-expiration and end-inspiration (Δtdi%)} could be used to predict extubation success (spontaneous breathing for > 48 hours) or failure in 63 mechanically ventilated patients and found:
  1. 27 patients were weaned with spontaneus breathing and 36 were weaned with pressure support
  2. for successful extubation, Δtdi% ≥30% had a
    1. sensitivity:  88%
    2. specificity:  71%
    3. positive predictive value:  91%
    4. negative predictive value:  63%
    5. area under the receiver operating characteristic curve:  0.79

Abstract:  DiNino. Diaphragm ultrasound as a predictor of successful extubation from mechanical ventilation. Thorax 2013;epublished December 23rd

Girard completed an observational substudy of the prospective multicentre randomised controlled PROSEVA study in patients with severe ARDS, comparing supine position (n=229) with prone position (n=237) ventilation for the development of pressure ulcers and found:

  1. no difference in ulcer incidence at baseline
  2. prone positioning was associated with
    • a trend towards increased incidence of pressure ulcers per days of invasive mechanical ventilation (P = 0.061)
      • 20.80 versus 14.26/1,000 days
    • increased incidence of pressure ulcers per ICU days (P = 0.002)
      • 13.92 versus 7.72/1,000 ICU days 
  3. covariates independently associated with the development of pressure ulcers were:
    • position group (OR 1.5408, P = 0.0653)
    • age >60 years (OR 1.5340, P = 0.0019)
    • female gender (OR 0.5075, P = 0.019)
    • body mass index of >28.4 kg/m2 (OR 1.9804, P = 0.0037)
    • Simplified Acute Physiology Score II at inclusion of >46 (OR 1.2765, P = 0.3158)

Other Studies of Interest

Meta Analyses

Observational Studies

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Study Critique

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Clinical Reviews











Non-Clinical Reviews


Basic Science Reviews

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I hope you find these brief summaries and links useful.

Have a great 2014



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