Newsletter 128 / May 18th 2014




Welcome to the 128th 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 inhaled antibiotics and traumatic brain injury; before-and-after interventional studies on telemedicine and delirium; meta analyses on noninvasive cardiac output monitors and high frequency oscillatory ventilation; and observational studies on perioperative vasoactive therapy for cardiac surgery and ICU-acquired weakness. Additional studies include meta analyses on active learning, neuraminidase inhibitors and central-line associated bloodstream infections, plus observational studies on inappropriate ICU care, vasopressor support in septic shock, preoperative anaemia, lung ultrasound and the Manchester Acute Coronary Syndrome Decision Rule, from Rick Body and colleagues at St Emlyns.

Editorials address REBOA, medical errors, general critical care, and mechanical ventilation. There are numerous commentaries, including papers on sedation, infection control, extracorporeal lung support and clinical informatics. There are also several case reports, including features on brain death and septic ketoacidosis.

Amongst the clinical review articles are papers on sleep in the ICU, acute coronary syndromes, continuous cardiac output monitoring, tetrastarches, pneumoperitoneum, enteral nutrition, estimating renal function, stress hyperglycaemia, hyperammonaemia, malignant hyperthermia, combination antibiotics, trauma and massive blood transfusion, hypotensive resuscitation, bedside ultrasonography, potentially ineffective care and a new section on paediatrics. There's even an entire trauma manual, from the Anaesthesia Trauma and Critical Care Course.

Pre-clinical review articles discuss murine models and neutrophil extracellular traps.

The topic for This Week's Papers is metabolic conditions, starting with a paper on noncirrhotic hyperammonaemic encephalopathy in tomorrow's Paper of the Day.

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Critical Care Reviews Meeting 2015

Next years meeting will be held on Friday, January 23rd, again at the Galgorm Resort and Spa, just outside Belfast. The theme of the meeting is to discuss recent major research and attempt to answer a single question - should we be implementing the results of this study? The Primary Investigators of some of the largest RCTs in the past 18 months will be there to discuss their studies and the implications for our practice. The first speaker to be announced is Niklas Nielsen, from Sweden, who published the Targeted Temperature Management Study (TTM study) in the New England Journal of Medicine last November. More exciting speakers will be announced over the next few weeks.

Free Open Access Medical Education (FOAM) Websites

There has been a number of developments amongst providers of free online medical education over the past week. Steve Mathieu and colleagues in Portsmouth have released a fantastic new site (The Bottom Line), providing structured appraisals of the major critical care studies. New critiques are being added on a daily basis. On a similar theme, the Critical Care Reviews Top 100 Studies has been updated, with further summaries added. Oli Flower and Matt McPartlin from Sydney have updated their superb site the Intensive Care Network, with a host of new podcasts recently added. Chris Nickson has just released a new site from the Alfred ICU in Melbourne, called Intensive. If you haven't checked out the online critical care community, take a look at some of these websites. There's even a major conference (Social Media and Critical Care, SMACC), which is simply fantastic and will be held in Chicago next year, almost one year to the day, May 20th to 22nd.

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Randomized Controlled Trials

Palmer and colleagues compared aerosolized antibiotics (aminoglycoside or vancomycin) with placebo in 42 critically ill, chronically mechanically ventilated patients with signs of respiratory infection, at high risk for respiratory multidrug-resistant organisms, and also receiving systemic antibacterial therapy, and found:
  1. aerosolized antibiotics were associated with
    • greater eradication of
      • bacteria present at randomization
        • 26/27 vs. 2/23 (P<0.001)
      • original resistant bacteria on culture and Gram stain at end of treatment
        • 14/16 vs. 1/11 (P<0.001)
    • no new drug resistance
    • reduced Clinical Pulmonary Infection Score (mean ± SEM)
      • 9.3 ± 2.7 to 5.3 ± 2.6 vs. 8.0 ± 23 to 8.6 ± 2.10; (P = 0.0008)
  2. placebo was associated with
    • increased development of resistant organisms (P=0.03)

Abstract:  Palmer. Reduction of Bacterial Resistance with Inhaled Antibiotics in the Intensive Care Unit. Am J Respir Crit Care Med 2014;189(10):1225-1233

In a multicentre, placebo controlled, European exploratory Phase II study, Schinzel and colleagues evaluated the safety and pharmacodynamics of 4-Amino-tetrahydrobiopterin (VAS203), a NO-synthase inhibitor in 32 patients with traumatic brain injury, and found:

  1. VAS203 was associated with
    • no significant 
      • physiological effects
        • intracranial pressure
        • cerebral perfusion pressure
        • brain metabolism
      • toxic effects
        • hepatic
        • haematological
        • cardiac
    • reduced therapy intensity level on day 6 (p<0.04)
    • higher
      • extended Glasgow Outcome Score at 6 months (p<0.01)
  2. transitory acute kidney injury (stage 2-3)
    • in 4 of 8 patients receiving the highest dose (30mg/kg)

Abstract:  Schinzel. NO-Synthase Inhibition with the Antipterin VAS203 improves Outcome in moderate and severe Traumatic Brain Injury: a Placebo-Controlled Randomised Phase II Trial (NOSTRA). J Neurotrauma 2014;epublished May 15th

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Before and After Studies

Nassar and colleagues compared patients treated in 8 American ICUs (intervention ICUs) before (n=1,708 patients) and after (n=1,647) the implementation of a telemedicine programme, and 3,584 patients treated in concurrent control ICUs that did not implement an telemedicine program, and found:
  1. no differences between intervention and control ICUs during the pre-TM and post-TM periods in
    • patient demographics
    • comorbid illnesses
  2. predicted ICU mortality rates were lower for intervention ICUs compared with control ICUs 
    • pre-TM (3.0% vs 3.6%; P = 0.02) 
    • post-TM (2.8% vs 3.5%; P  < 0.001)
  3. implementation of ICU telemedicine was associated with a
    • no significant decline in mortality (pre vs post TM)
      • unadjusted ICU
        • intervention ICU
          • 2.9% vs 2.8% (P =0 .89)
        • control ICUs
          • 4.0% vs 3.4% (P = 0.31)
      • in-hospital
      • unadjusted 30-day mortality rates 
        • intervention ICU
          • 7.7% vs 7.8% (P = 0.91)
        • control ICUs
          • 12.0% vs 10.2% (P = 0.08)
    • no change in length of stay

Abstract:  Nassar. Impact of an Intensive Care Unit Telemedicine Program on Patient Outcomes in an Integrated Health Care System. JAMA Intern Med 2014;epublished May 12th

Patel and colleagues evaluated delirium and sleep before (n=167) and after (n=171) the implementation of a bundle of non-pharmacological interventions, consisting of environmental noise and light reduction designed to reduce nighttime disturbance, and found:

  1. compliance with the interventions was > 90%
  2. the bundle of interventions was associated with (before vs after; mean/SD)
    • increased
      • sleep efficiency index
        • 60.8 (3.5) vs 75.9 (2.2); p = 0.031
    • reduced
      • sound
        • 68.8 (4.2) dB vs 61.8 (9.1) dB; p = 0.002 
      • light levels
        • 594 (88.2) lux vs 301 (53.5) lux; p = 0.003
      • number of awakenings caused by care activities
        • 11.0 (1.1) vs 9.0 (1.2); p = 0.003
      • incidence of delirium
        • 55/167 (33%) before vs 24/171 (14%); p < 0.001
      • time spent in delirium
        • 3.4 (1.4) days vs 1.2 (0.9) days; p = 0.021
    • increases in sleep efficiency index were associated with a
      • lower odds ratio of developing delirium (OR 0.90, 95% CI 0.84 to 0.97)

Abstract:  Patel. The effect of a multicomponent multidisciplinary bundle of interventions on sleep and delirium in medical and surgical intensive care patients. Anaesthesia 2014;69:540–549

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Meta Analyses

Kim et al pooled data from 28 studies (n=919), comparing continuous noninvasive arterial pressure monitoring with invasive arterial pressure monitoring, and found:
  1. overall random-effect pooled bias and SD
    • systolic arterial pressure:
      • −1.6 ± 12.2 mmHg (95% limits of agreement −25.5 to 22.2 mmHg)
    • diastolic arterial pressure:
      • 5.3 ± 8.3 mmHg (−11.0 to 21.6 mmHg)
    • mean arterial pressure:
      • 3.2 ± 8.4 mmHg (−13.4 to 19.7 mmHg)
  2. In 14 studies focusing on currently commercially available devices, bias and SD were
    • systolic arterial pressure:
      • −1.8 ± 12.4 mmHg (−26.2 to 22.5 mmHg)
    • diastolic arterial pressure:
      • 6.0 ± 8.6 mmHg (−10.9 to 22.9 mmHg) 
    • mean arterial pressure:
      • 3.9 ± 8.7 mmHg (−13.1 to 21.0 mmHg)
  3. The authors concluded
    • the accuracy and precision of continuous noninvasive arterial pressure monitoring devices exceed acceptable limits as defined by the Association for the Advancement of Medical Instrumentation

Abstract:  Kim. Accuracy and Precision of Continuous Noninvasive Arterial Pressure Monitoring Compared with Invasive Arterial Pressure: A Systematic Review and Meta-analysis. Anesthesiology 2014;120(5):1080–1097

Maitra et al reviewed 7 randomized controlled trials comparing high-frequency oscillatory ventilation with conventonal mechanical ventilation in 1,759 patients, and found:
  1. high-frequency oscillatory ventilation was associated with
    • no mortality improvement 
      • in-hospital/30-day mortality benefit 
        • risk ratio 0.96; 95% CI 0.77 to 1.19; P = 0.70
    • a trend to prolonged duration of mechanical ventilation
      • mean difference 1.18 days; 95% CI 0.00 to 2.35 days; P = 0.05
    • no difference in
      • duration of intensive care unit stay
        • mean difference 1.24 days; 95% CI -0.08 to 2.56 days; P = 0.06 
      • requirement for neuromuscular blockerade
      • incidence of barotrauma
      • incidence of refractory hypotension
    • reduced incidence of refractory hypoxemia
      • risk ratio, 0.60; 95% CI 0.39 to 0.93; P = 0.02

Abstract:  Maitra. High-frequency Ventilation Does Not Provide Mortality Benefit in Comparison with Conventional Lung-protective Ventilation in Acute Respiratory Distress Syndrome: A Meta-analysis of the Randomized Controlled Trials. Anesthesiology 2014;epublished May 14th

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Observational Studies

Nielsen and colleagues performed a retrospective propensity-matched cohort study using prospectively collected data from 6,005 consecutive cardiac surgery cases, examining the association between intra- and postoperative use of inotropes and mortality and postoperative complications, and found:

  1. perioperative inotropic/vasopressor exposure
    • exposed - 35% (n=2,097)
    • not exposed - 65% (n=3,908)
  2. in the propensity-matched cohort (n=2,340)
    • mortality
      • 30-day mortality: 3.2% 
      • 1-yr mortality: 7.6%.
    • inotrope exposure was associated with
      • increased mortality
        • 30-day mortality 
          • adjusted hazards ratio 3.7; 95% CI 2.1 to 6.5
        • 1-yr mortality rate
          • adjusted hazards ratio 2.5; 95% CI 1.8 to 3.5
      • increased adverse events
        • myocardial infarction 2.4%
          • adjusted odds ratio 2.1; 95% CI 1.4 to 3.0
        • stroke 2.8%
          • adjusted odds ratio, 2.4; 95% CI 1.4 to 4.3
        • renal replacement therapy 23.9%
          • adjusted odds ratio 7.9; 95% CI 3.8 to 16.4
        • arrhythmia 35%

Hermans et al perfomed a 1:1 propensity-matched analysis evaluating the effects of ICU-acquired weakness in 244 critically ill patients enrolled in a randomized controlled trial, and staying ≥ 8 days in the ICU, and found:
  1. basic data
    • 78.6% were admitted to a surgical ICU
    • 55% (227/415) of long-stay assessable ICU patients were weak
  2. weak patients had a
    • lower likelihood for
      • weaning from mechanical ventilation
        • HR 0.709, 95% CI 0.549 to 0.888, P=0.009
      • ICU discharge
        • HR 0.698, 0.553 to 0.861, P=0.008
      • hospital discharge
        • HR:0.680, 95% CI 0.514 to 0.871; ,P=0.007
    • increased
      • In-hospital costs/patient
        • +30.5%, +5,443 euro/patient, p=0.04
      • 1-year mortality
        • 30.6% versus 17.2%, p=0.015 .
  3. The 105/227 (46%) weak patients not matchable to not-weak patients had even worse prognosis and higher costs
  4. The 1-year risk of death was further increased if weakness persisted and was more severe as compared with recovery of weakness at ICU discharge (p<0.001)

Abstract:  Hermans. Acute outcomes and 1-year mortality of ICU-acquired weakness: A cohort study and propensity matched analysis. Am J Respir Crit Care Med 2014;epublished May 13th

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Additional Studies

Meta Analyses

Observational Studies

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Case Reports

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Clinical Review Articles












Anaesthesia Trauma and Critical Care Course Manual (8th Edition)



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Pre-Clinical Review Articles

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I hope you find these brief summaries and links useful.

Until next week