Newsletter 111 / January 19th 2014




Welcome to the 111th 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's research studies include randomized controlled trials on parenteral fish oil, coupled plasma filtration adsorption, plus fluids in both cardiac and colorectal surgery; meta analyses address mannitol for the prevention of acute kidney injury, risk of infection with therapeutic hypothermia and macrolide therapy for community-acquired pneumonia; observational studies focus on the prognostic significance of right ventricular dysfunction in pulmonary embolism, hyperoxia in stroke patients and the effects of compliance with the Trauma Brain Foundation guidance on intracranial pressure monitoring. Links are provided to another 13 studies of interest.

There is a single report from the American Department of Defense Neurotrauma Pharmacology Working Group on pharmacotherapy for traumatic brain injury, while editorials discuss ventilator-associated events and airway management. Amongst the clinical review articles are papers on ICP management, sedation, sleep, sonographic evaluation of volume responsiveness, acute coronary syndrome, a critical care cardiology update, PEEP, lung ultrasound, acute-on-chronic liver failure, bleeding on dabigatran, and penetrating neck trauma. One basic science review article looks at statistical methods to deal with missing data. If you prefer a break from all the serious reading, try the general interest article, providing a fascinating discussion on the possible catecholamine cardiomyopathy suffered by Neil Armstrong whilst in space and on the moon.

The topic for This Week's Papers is the critical illness adaptative response, starting with a paper on multi-organ failure in tomorrow's Paper of the Day.


Critical Care Reviews Meeting

The long wait is almost over and it's now just days to the Critical Care Reviews Meeting 2014.  Late registration is still available online. 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. If you can't make it, follow #CCRMeeting for live updates throughout the day.


SMACC GOLD March 19-21st, 2014, Gold Coast, Queensland, Australia

This major international conference, also in it's second year, is a must for those active in the online critical care community. Webmasters of the most prominent critical care websites and blogs will descend on the beautiful Gold Coast for an amazing get together of like-minded people in a totally different style of conference.

Evidence-Based Medicine Workshop at SMACCgold

Several workshops are still available for registration, including the Evidence-Based Medicine workshop I'll be helping run along with Simon Carley, Professor of Emergency Medicine in Manchester, and Rick Body, a fellow EM consultant in Manchester. They run the superb evidence-based medicine websites St. Emelyn's and BestBets and are experienced researchers with a vast publication portfolio. Sessions include Practical Critical Appraisal, EBM in Clinical Practice, Demystifying Statistics, and Making Journal Club Work. Delegates will learn the fundamentals of EBM, and immediately put it to effect, producing a critical appraisal BestBet which will be published. If you're coming to SMACCgold, don't miss this opportunity to improve a critical skill - the ability to appraise the literature, strengthen your decision making and enhance the care you provide to your patients.

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Randomized Controlled Trials

Hall and colleagues completed a randomized control trial comparing parenteral ω-3 (a fish oil) with standard medical care in 60 critically ill patients with sepsis, and found:

  1. group baseline demographics were similar
  2. parenteral ω-3 was associated with
    • reductions of
      • 1° outcome
        • new organ dysfunction
          • Δ-SOFA
            • 2.2 ± 2.2 vs. 1.0 ± 1.5, P = 0.005
          • maximum-SOFA
            • 10.1 ± 4.2 vs. 8.1 ± 3.2, P = 0.041
      • 2° outcomes
        • maximum CRP
          • 186.7 ± 78 vs. 141.5 ± 62.6, P = 0.019
        • mortality in the strata of less severe sepsis (P =0.042)
    • no significant effect on
      • 2° outcomes
        • length of stay

Abstract:  Hall. A Randomized Controlled Trial Investigating the Effects of Parenteral Fish Oil on Survival Outcomes in Critically Ill Patients With Sepsis: A Pilot Study. JPEN J Parenter Enteral Nutr 2014;epublished January 9th

Livigni and colleagues completed an Italian prospective, multicenter, randomised, open-label, parallel group, superiority clinical trial, comparing coupled plasma filtration adsorption (daily for 5 days, lasting ≥ 10 h/day) with standard care in 192 critically ill patients with septic shock, and found:

  1. the study was terminated early for futility
  2. 1° outcome
    • no difference in hospital mortality
      • controls 47.3% versus CPFA 45.1% ; p=0.76
  3. 2° outcomes
    • no difference in
      • new organ failures
        • controls 55.9% vs. CPFA 56.0%; p=0.99
      • ICU free days during the first 30 days
        • controls 6.8 vs. CPFA 7.5; p=0.35
  4. a priori planned subgroup analysis
    • reduced mortality if CPFA dose >0.18 L/kg/day
      • OR 0.36, 95% CI 0.13 to 0.99

Full Text:  Livigni. Efficacy of coupled plasma filtration adsorption (CPFA) in patients with septic shock: A multicenter randomised controlled clinical trial. BMJ Open 2014;4:e003536

Skhirtladze et al compared the effects of albumin 5%, 6% hydroxyethyl starch 130/0.4, and Ringer's lactate (all up to 50 ml kg−1 day−1) as the main infusion fluid perioperatively, on blood loss and coagulation in 240 patients undergoing elective cardiac surgery, and found:

  1. 1° outcome
    • no difference in chest tube drainage over 24 h
  2. 2° outcome
    • no difference in median cumulative blood loss
      • HA 835, HES 700, RL 670 ml
    • Ringers lactate was associated with
      • reduced blood product requirement
        • RL 35%, HA 62%, HES 64%; P=0.0003
      • greater study solution requirement
    • albumin was associated with
      • a smaller perioperative fluid balance 
        • HA group 6.2 (2.5) litre, HES 7.4 (3.0) L, RL 8.3 (2.8) L, P<0.0001
    • albumin and HES were associated with
      • reduced clot formation and clot strength
      • increases in serum creatinine

Abstract:  Skhirtladze. Comparison of the effects of albumin 5%, hydroxyethyl starch 130/0.4 6%, and Ringer's lactate on blood loss and coagulation after cardiac surgery.  Br J Anaesth 2014;112(2):255-264

Yates et al compared balanced 6% HES (130/0.4, Volulyte) with balanced crystalloid (Hartmann's solution) as haemodynamic optimization fluid in 202 medium to high-risk patients undergoing elective colorectal surgery, and found:

  1. 1° outcome
    • no difference in GI morbidity on postoperative day 5
      • HES 30% vs crystalloid 32%
      • adjusted odds ratio=0.96; 95% CI 0.52–1.77
  2. 2° outcomes
    • crystalloid therapy was associated with
      • greater fluid requirement
        • 3175 (2000–3700) vs 1875 (1500–3000) ml, P<0.001
      • greater 24 h fluid balance
        • +4226 (3251–5779) vs +3610 (2443–4519) ml, P<0.001
    • no difference in the incidence of postoperative complications

Abstract:  Yates. Crystalloid or colloid for goal-directed fluid therapy in colorectal surgery.  Br J Anaesth 2014;112(2):281-289

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Meta Analyses

Yang and colleagues pooled data from nine randomized controlled trials (n=626) comparing the effects of IV mannitol plus volume expansion, with volume expansion alone for the prevention of acute kidney injury, and found:
  1. mannitol was
    • not associated with a reduction in serum creatinine
      • mean difference 1.63, 95% CI −6.02 to 9.28
    • was associated with
      • increased serum creatinine in patients having radiocontrast
        • mean difference 17.90, 95% CI 8.56 to 27.24
      • reduced acute renal failure or the need of dialysis in recipients of renal transplantation
        • RR 0.34, 95% CI 0.21 to 0.57, NNT 3.03, 95% CI 2.17 to 5.00
      • no effect in non-renal transplant patients at high risk of AKI
        • RR 0.29, 95% CI 0.01 to 6.60

Full Text:  Yang. Intravascular Administration of Mannitol for Acute Kidney Injury Prevention: A Systematic Review and Meta-Analysis. PLoS ONE 2014;9(1):e85029

Geurts and colleagues review 23 randomized controlled trials (n=2,820) of therapeutic hypothermia (n=1,398) induced in adults for any indication, and which reported the prevalence of infection, and found:
  1. studies had a high risk of bias
  2. hypothermia was
    • not associated with increased infection rate
      • rate ratio 1.21; 95% CI 0.95–1.54
    • associated with an increased risk of
      • pneumonia
        • risk ratio 1.44; 95% CI 1.10–1.90
      • sepsis
        • risk ratio 1.80; 95% CI 1.04–3.10

Abstract:  Geurts. Therapeutic Hypothermia and the Risk of Infection: A Systematic Review and Meta-Analysis. Crit Care Med 2014;42(2):231-242

Sligl et al pooled 28 observational studies (n=9,850) comparing macrolide therapy with other regimens in critically ill patients with community-acquired pneumonia, and found:
  1. macrolide use was associated with
    • lower mortality compared with nonmacrolides
      • 21% vs 24%; risk ratio 0.82; 95% CI 0.70–0.97; p = 0.02; I2 = 63%
      • even excluding macrolide monotherapy
        • 21% vs 23%; risk ratio 0.84; 95% CI 0.71–1.00; p = 0.05; I2 = 60%
    • comparing broadly guideline-concordant regimens, there was a trend to improved mortality
      • beta-lactam/macrolide therapy 20%  vs beta-lactam/fluoroquinolone 23%; risk ratio 0.83; 95% CI 0.67–1.03; p = 0.09; I2 = 25%
    • pooling adjusted risk estimates from eight studies, macrolide therapy was still associated with a significant reduction in mortality
      • risk ratio 0.75; 95% CI 0.58–0.96; p = 0.02; I2 = 57%

Abstract:  Sligl. Macrolides and Mortality in Critically Ill Patients With Community-Acquired Pneumonia: A Systematic Review and Meta-Analysis. Crit Care Med 2014;42(2):420-432

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Observational Studies

Jiménez et al undertook a prospective, multicentre observational cohort study assessing the prognostic value of right ventricular dysfunction (ratio of the RV to the LV short axis diameter > 0.9 assessed by multidetector CT) in 848 normotensive patients with pulmonary embolism, and found

  1. RV dysfunction was present in 63% (n=533)
  2. patients with RV dysfunction on MDCT, compared with those without,
    • had greater
      • incidence of echocardiographic RV dysfunction 
        • 31% vs. 9.2%; p<0.001
      • higher brain natriuretic peptide
        • 269±447 vs 180±457 pg/ml, p<0.001
      • troponin
        • 0.10±0.43 vs 0.03±0.24 ng/ml, p=0.001
    • had similar incidences of
      • death
        • 4.7% vs 4.3%; p=0.93
      • complications
        • 3.9% vs 2.3%; p=0.30

Full Text:  Jiménez. Prognostic significance of multidetector CT in normotensive patients with pulmonary embolism: results of the protect study. Thorax 2014;69:109-115

Rincon et al performed a 5 year retrospective, multicenter cohort study, examining the association between hyperoxia and mortality in 2,894 stroke patients requiring mechanical ventilation, and found:
  1. the patient cohort consisted of
    • conditions
      • acute ischemic stroke (19%),
      • subarachnoid hemorrhage (32%)
      • intracerebral hemorrhage (49%)
    • oxygenation
      • normoxia  (38%)
      • hypoxia (PaO2 < 60 mmHg / 8 kPa) (46%)
      • hyperoxic (PaO2 > 300 mmHg / 40 kPa) (16%)
  2. mortality was higher in the hyperoxia group as compared with
    • normoxia group
      • crude odds ratio 1.7; 95% CI 1.3-2.1; p < 0.0001
    • hypoxia group
      • crude odds ratio 1.3; 95% CI 1.1–1.7; p < 0.01
  3. exposure to hyperoxia was independently associated with in-hospital mortality
    • adjusted odds ratio 1.2; 95% CI 1.04–1.5

Abstract:  Rincon. Association Between Hyperoxia and Mortality After Stroke: A Multicenter Cohort Study. Crit Care Med 2014;42(2):387-396

Roberts and colleagues completed a prospective, observational study evaluating compliance with, and efficacy from, the Brain Trauma Foundation guidance on intracranial pressure monitoring in 216 patients with severe traumatic brain injury, and found: 

  1. guideline compliance was 46.8% 
  2. patients with subarachnoid hemorrhage and post craniectomy/craniotomy were significantly more likely to undergo ICP monitoring
  3. the avoidance of ICP monitor placement was associated with
    • the presence of
      • hypotension
      • coagulopathy
      • increasing age
    • increased mortality 
      • in-hospital
        • 53.9% vs 32.7%, adjusted p = 0.019
      • mortality due to brain herniation
        • 21.7% vs 12.9%, adjusted p = 0.046
    • reduced lengths of stay
      • ICU 
      • hospital

Abstract:  Talving. Intracranial pressure monitoring in severe head injury: compliance with Brain Trauma Foundation guidelines and effect on outcomes: a prospective study. J Neurosurg 2013;119(5):1248-54 

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Other Studies of Interest

Meta Analyses

Observational Trials

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Guideline, Statements & Reports