Newsletter 129 / May 25th 2014




Welcome to the 129th 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 is the second newsletter of the week, with the major studies from the American Thoracic Society meeting included in a supplemental edition last Monday.

This week's research studies include randomized controlled trials on contrast-induced acute kidney injury, subarachnoid haemorrhage, COPD and hepatic encephalopathy; one meta analysis on high frequecy oscillatory ventilation; and observational studies on ventilator-associated conditons and renal replacement therapy. Additional studies investigate postoperative pancreatic fistulae, surgical checklists, stroke, analphylaxis, super-refractory staus epilepticus, fluid resuscitation, intraoperative cardiac arrest and ARDS phenotypes.

This week there are two guidelines on atrial fibrillaton and ultrasound training, and one study critique looking at β blockade in septic shock. Editorials address nursing and carbapenemase gram negative bacteria;  commentaries focus on MERS-CoV, defensive medicine, big data and physician involvement in execution.  Amongst the clinical review articles are numerous papers from an open access journal Current Emergency and Hospital Medicine Reports, as well as papers on subarachnoid haemorrhage, dexmedetomidine, inotropes, mineralocorticoid receptor antagonists, respiratory mechanics, pneumatosis intestinalis, liver failure, diabetic ketoacidosis, intraoperative hypothermia, frostbite, dengue shock syndrome and diagnostic errors.

A single basic science review article discusses sample size, while a non-clinical review discusses professionalism.

The topic for This Week's Papers is asthma, starting with a paper on mechanical ventilation in tomorrow's Paper of the Day.


Critical Care Reviews Meeting 2015

Following on from the results of SAILS at the ATS last Sunday, I'm delighted to announce the second guest speaker at the 2015 Critical Care Reviews Meeting will be local Professor, Danny McAuley, PI of the multi-centre HARP-2 study, investigating simvastatin in ARDS. HARP-2 will hopefully be presented towards the end of 2014, putting the 2015 Critical Care Reviews Meeting in prime position for a discussion not just on statins in ARDS, but given the plethora of statin studies in the past 12 months, including 3 in this newsletter alone, a discussion on statins in general in the critically ill. Prof McAuley joins Dr Niklas Nielsen, PI of the Targeted Temperature Management Study, on a high powered faculty giving cutting edge insights into the most recent critical care advances. This is arguably one of the most contemporary critical care meetings around, and is entirely not-for-profit.

SMACC Chicago

The incredible SMACC conference team continue to deliver superb, free critical care education, with the first presentations from the smaccGOLD conference now online - check out their vimeo channel or the Intensive Care Network for these, and other upcoming videos. Also, the official flyer for the third installment of this conference is now out, as the venue moves from Australia to the USA.

  • Save the date - May 19th to 22nd 2015, McCormick Place, Chicago. See you there.

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Randomized Controlled Trials

Brar and colleagues completed a randomised, parallel-group, comparator-controlled, single-blind phase 3 trial, comparing a left ventricular end-diastolic pressure-guided fluid administration protocol with a standard fluid administration protocol in 396 adults undergoing cardiac catheterisation with an estimated glomerular filtration rate of 60 mL/min/1·73 m2 or less, and one or more of several risk factors, and found:

  1. the new fluid protocol was associated with
    • a reduced incidence of contrast-induced acute kidney injury 
    • 6·7% vs. 16·3%; RR 0·41, 95% CI 0·22 to 0·79; p=0·005
  2. hydration treatment was terminated prematurely because of shortness of breath in three patients in each group

Abstract:  Brar. Haemodynamic-guided fluid administration for the prevention of contrast-induced acute kidney injury: the POSEIDON randomised controlled trial. Lancet 2014;383(9931):1814-1823

Kirkpatrick and colleagues completed an international, multicentre, randomised, double-blind trial, comparing simvastatin 40 mg (n=391) with placebo (n=412) once a day for up to 21 days, in 803 adults within 96 hours of  subarachnoid haemorrhage, and found:

  1. no between-group difference in
    • incidence of favourable modified Rankin Scale (mRS) score, obtained by questionnaire at 6 months (1° outcome)
      • simvastatin 271 vs placebo 289
      • OR 0·97, 95% CI 0·75 to 1·25; p=0·803
    • mortality at 6 months
      • simvastatin 10% (n=37) vs placebo 9% (n=35); log-rank p=0·592
    • serious adverse events
      • 18% vs 18%

Abstract:  Kirkpatrick. Simvastatin in aneurysmal subarachnoid haemorrhage (STASH): a multicentre randomised phase 3 trial. Lancet Neurology 2014;epublished May 16th

Criner and colleagues completed a multi-centre trial compared simvastatin 40mg once daily with placebo in 885 adults aged 40 to 80 years with COPD, and found:

  1. basic data
    • 44% were female
    • age: 62.2±8.4 years (mean (±SD))
    • FEV1: 41.6±17.7% of the predicted value
    • smoking history of 50.6±27.4 pack-years
  2. there was no between group difference in
    • mean number of exacerbations per person-year
      • simvastatin 1.36±1.61 exacerbations vs placebo 1.39±1.73 exacerbations (P=0.54)
    • median number of days to first exacerbation
      • simvastatin 223 days (95% CI 195 to 275) vs placebo 231 days (95% CI 193 to 303) (P=0.34)
    • number of nonfatal serious adverse events per person-year
      • simvastatin 0.63 events vs placebo 0.62 events
    • mortality
      • simvaststin n=28 vs placebo n=30 (P=0.89)

Full Text:  Criner. Simvastatin for the Prevention of Exacerbations in Moderate-to-Severe COPD (STATCOPE Study). New Eng J Med 2014;epublished May 18th

Lunia and colleagues performed a single-centre, randomized controlled trial in India, evaluating probiotics (1 × 108 colony-forming units, 3 times daily; n=86) in 160 patients with cirrhosis without overt hepatic encephalopathy, and found

  1. demographics
    • age 48.6 ± 11.1 years
    • gender: 96 men / 64 women
    • Child–Turcotte–Pugh (CTP)
      • class A: n=25 / class B: n=51 / class C: n=84
  2. groups were similar at baseline
  3. mean follow ups
    • probiotics 38.6 ± 8.80 weeks vs controls 40.3 ± 9.8 weeks
  4. probiotics were associated with
    • a significant reduction in
      • the development of overt hepatic encephalopathy (1° outcome)
      • hazard ratio 2.1; 95% CI 1.31 to 6.53; P<0.05
  5. there was no difference in
    • mortality
      • probiotics n=6 vs controls n=7 (P = 0.81)
  6. compared with baseline, three months of probiotic administration was associated with significantly
    • reduced levels of
      • arterial ammonia
      • small intestinal bacterial overgrowth
      • orocecal transit time
    • increased
      • psychometric hepatic encephalopathy scores
      • increased critical flicker fusion threshold assessment

Full Text:  Lunia. Probiotics Prevent Hepatic Encephalopathy in Patients With Cirrhosis: A Randomized Controlled Trial. Clinical Gastroenterology and Hepatology 2014;12(6):1003–1008.e1

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Meta Analysis

Huang et al pooled data from five randomized controlled trials, evaluating high frequency oscillatory ventilation in 1,508 adult patients with acute respiratory distress syndrome, and found:

  1. HFOV was associated with
    • improved oxygenation on day one of therapy
      • 4 studies; 24% higher; 95% CI 11 to 40%; P <0.01
    • no mortality reduction
      • 5 studies; risk ratio 1.04; 95% CI 0.83 to 1.31; P = 0.71
    • potential harm
      • 2 studies terminated early; RR 1.33; 95% CI 1.09 to 1.62; P <0.01
    • no difference in risk of
      • barotrauma
        • 5 studies; RR 1.19; 95% CI 0.83 to 1.72; P = 0.34
      • unfavorable hemodynamics
        • 5 studies; RR 1.16; 95% CI 0.97 to 1.39; P = 0.12

Full Text:  Huang. Efficacy and adverse events of high frequency oscillatory ventilation in adult patients with acute respiratory distress syndrome: a meta-analysis. Critical Care 2014;18:R102

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 Observational Studies

André et al undertook a cohort study, consisting of 81 episodes of antimicrobial treatment for ventilator-associated pneumonia, investigating whether delays in antimicrobial administration, after patients meet ventilator-associated complications (VAC) criteria, leads to worse outcomes, and found:

  1. 60% of patients with VAC had a delay of 48 hours before the initiation of antimicrobials
  2. delayed antimicrobial administration, in comparison with immediate administration, was not associated with
    • ICU mortality
      • OR 0.71, 95% CI 0.11 to 4.48, p = 0.701
    • risk of treatment failure or superinfection 
      • HR 0.95, 95% CI 0.42 to 2.19, p = 0.914

Full Text:  André. Timing of Antimicrobial Therapy after Identification of Ventilator-Associated Condition Is Not Associated with Mortality in Patients with Ventilator-Associated Pneumonia: A Cohort Study. PLoS One 2014;9(5):e97575

Ronco and colleagues developed the world's first miniaturised continuous renal replacement therapy machine (CARPEDIEM - Cardio-Renal Pediatric Dialysis Emergency Machine) for neonates and small infants, and reported:

  1. main characteristics of CARPEDIEM 
    • low circuit priming volume (< 30 mL)
    • miniaturised roller pumps
    • accurate ultrafiltration control via calibrated scales with a precision of 1 g
  2. in the treatment of a 2·9 kg neonate with haemorrhagic shock, multiple organ dysfunction, and severe fluid overload for more than 400 h with the CARPEDIEM
    • using
      • continuous venovenous haemofiltration
      • single-pass albumin dialysis
      • blood exchange
      • plasma exchange
    • the following were all managed safely and effectively
      • fluid overload (65%)
      • raised creatinine
      • bilirubin concentrations
    • the neonate survived and was discharged from hospital with only mild renal insufficiency that did not require renal replacement therapy

Abstract:  Ronco. Continuous renal replacement therapy in neonates and small infants: development and first-in-human use of a miniaturised machine (CARPEDIEM). Lancet 2014;383(9931):1807-1813

Boyer and colleagues completed a 12 month prospective cohort study on 1,209 patients ventilated for two or more calendar days, seeking to determine the clinical utility of the new Centers for Disease Control and Prevention ventilator-associated conditions (VACs) criteria, and found:

  1. VAC
    • incidence 5.5% (n=67)
      • 7.0 per 1000 ventilator days
    • of which
      • infection-related VAC (IVAC) 50.7% (n=34)
        • 3.6 per 1,000 ventilator days
    • associated with
      • increased mortality
        • 65.7% vs 14.4%; P < 0.001
    • 37.3% adjudicated to represent potentially preventable events
    • The most common cause of VACs included
      • IVACs (50.7%),
      • acute respiratory distress syndrome (16.4%)
      • pulmonary edema (14.9%)
      • atelectasis (9.0%).
  2. IVAC
    • probable VAP: 44.1%
    • possible VAP: 17.6%.
  3. VAP
    • 86 episodes of VAP occurred in 84 patients
      • 10 per 1,000 ventilator days
    • sensitivity of the VAC criteria for the detection of VAP
      • 25.9% (95% CI 16.7% to 34.5%)

Abstract:  Boyer. A prospective evaluation of ventilator-associated conditions and infection-related ventilator-associated conditions. Chest 2014;epublished May 22nd

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Additional Studies

Randomized Controlled Trials

Meta Analysis

Observational Studies

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Guidelines & Position Statements












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Basic Science 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