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Newsletter 136 / July 13th 2014




Welcome to the 136th 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 perioperative goal-directed haemodynamic management, point-of-care ultrasonography in the ED, triclosan-coated PDS Plus sutures for the prevention of surgical site infections, oxygen delivery post extubation, nutrition in acute lung injury; plus an update on the TOBY trial (Total Body Hypothermia for Neonatal Encephalopathy Trial); an interventional study on fingolimod therapy in intracerebral haemorrhage; and observational studies on linezolid plasma concentrations, and the effects of medical/nursing staffing on patient outcomes. Amongst the various Interventional study are papers on acute kidney injury and maternal sepsis.

This week's guidelines address perioperative renal transplant management, anaphylaxis, and regional anaesthesia in patients in taking anticoagulants.

Editorials focus on neurotrauma, spirituality and physician burnout; commentaries look at patient safety, handheld ultrasound use, capital punishment and the nocebo effect. A paper on p values completes a new addition to the site, a massive series of 224 worked explanations on statistics and research methodology by Philip Sedgwick, and published over the past 5 years in the BMJ. There is one case report on mobilisation in a patient undergoing CRRT and correspondence in the New England Journal of Medicine on the recent TOPCAT study.

Amongst the clinical review articles are papers on remimazolam, the processed EEG, cardiogenic shock, temporary transvenous cardiac pacing, video laryngoscopes, lung ultrasound, pulse oximetry, variceal haemorrhage, portopulmonary syndrome, extracorporeal liver support, vascular access for dialysis, oral anticoagulants, and preoperative evaluation.

Continuing our focus on excellent open access critical care journals, the topic for This Week's Papers is a collection from the Journal of the Intensive Care Society, starting with a paper on sedation interruption in tomorrow's Paper of the Day.

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Upcoming Meetings

Critical Care Reviews Meeting 2015

I'm delighted to add a late addition to the faculty for the 2015 Critical Care Reviews Meeting, being held in association with the Northern Ireland Intensive Care Society. Clifford Deutschman from Philidelphia, the immediate past president of the Society of Critical Care Medicine, will join Niklas Nielsen, Eddie Fan, Danny McAuley, Kathy Rowan, Eamon McCoy, John Hinds and a host of local intensivists to discuss the biggest research findings of the past year. The meeting will be held on Friday January 23rd, again 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.

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.

43rd Medical Emergencies Course for Trainee Doctors

Mervyn Singer, a guest speaker at the 2014 Critical Care Reviews Meeting, is hosting the 43rd Medical Emergencies Course for Trainee Doctors on the weekend of October 4th & 5th, 2014, at UCL in central London. Further details, including the programme and online registration can be found here.

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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.

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

Pestaña and colleagues completed a pragmatic, multi-centre study in 142 patients undergoing general surgery, comparing a noninvasive cardiac output monitor guided hemodynamic protocol, including fluid administration and vasoactive drugs, with standard practice, and found:

  • the interventional protocol was associated with
    • an increase in the number of
      • colloid boluses (2.4 ± 1.8 vs 1.3 ± 1.4; P < 0.001)
      • packed red blood cell units (0.6 ± 1.3 vs 0.2 ± 0.6; P = 0.019)
      • dobutamine use (p < 0.001)
        • intraoperatively: 25% vs 1.4%
        • postoperatively: 19.4% vs 0%
    • reduced
      • reoperations (5.6% vs 15.7%; P = 0.049)
    • no statistically significant differences in
      • overall fluid administration
      • overall complications (40% vs 41%)
        • relative risk 0.99; 95% CI 0.67 to 1.44; P = 0.397
      • length of stay (11.5 [8-15] vs 10.5 [8-16]; P = 0.874)
      • time to first flatus (62 hours [40-76] vs 72 hours [48-96]; P = 0.180)
      • wound infection (7 vs 14; P = 0.085)
      • anastomotic leaks (2 vs 5; P = 0.23)
      • mortality (4.2% vs 5.7%; P = 0.67)

Conclusion: The use of a perioperative goal-directed haemodynamic protocol in major abdominal surgery was not associated with reductions in overall complications, length of hospital stay, or mortality.

Abstract:  Pestaña. Perioperative Goal-Directed Hemodynamic Optimization Using Noninvasive Cardiac Output Monitoring in Major Abdominal Surgery: A Prospective, Randomized, Multicenter, Pragmatic Trial: POEMAS Study (PeriOperative goal-directed thErapy in Major Abdominal Surgery). Anesth Analg 2014;epublished July 9th

Laursen and colleagues completed a single centre study, comparing a diagnostic strategy of point-of-care ultrasonography (heart, lungs, and deep veins) plus usual initial diagnostic testing (n=160), with usual initial diagnostic testing alone (n=160), in 320 patients with respiratory symptoms or chest pain, and found:

  • the point-of-care ultrasonography strategy was associated with
    • at 4 h after admission to the emergency department
      • increased
        • correct presumptive diagnoses (p<0·0001)
          • 88·0% (95% CI 82·8 to 93·1) vs 63·7% (95% CI 56·1 to 71·3)
        • absolute effect 24·3% (95% CI 15·0 to 33·1) 
        • relative effect 1·38 (95% 1·01 to 1·31)
    • no adverse events were reported

Conclusion:  Point-of-care ultrasonography in the emergency department was associated with increased correct presumptive diagnoses in patients with respiratory symptoms or chest pain.

Abstract:  Laursen. Point-of-care ultrasonography in patients admitted with respiratory symptoms: a single-blind, randomised controlled trial. Lancet Respiratory Medicine 2014;epublished July 4th

Diener et al completed a German multicentre, randomised controlled group-sequential superiority trial, comparing triclosan-coated sutures (PDS Plus, n=607) with uncoated sutures (PDS II, n=617) for abdominal fascia closure in 1,224 patients undergoing elective midline laparotomy, and found:

  • groups were similar at baseline
  • there were no statistical difference in
    • occurrence of surgical site infections
      • PDS Plus group: 14·8% vs PDS II group: 16·1%
        • OR 0·91, 95% CI 0·66 to 1·25; p=0·64
    • serious adverse events
      • PDS Plus group: 25·0% vs PDS II group: 22·9%; p=0·39

Conclusion:  Abdominal wall closure with triclosan-coated PDS Plus sutures was not associated with reductions in surgical site infections in comparison with uncoated sutures

Abstract:  Diener. Effectiveness of triclosan-coated PDS Plus versus uncoated PDS II sutures for prevention of surgical site infection after abdominal wall closure: the randomised controlled PROUD trial. Lancet 2014;384(9938):142-152

Maurizio and colleagues completed an open-label trial, comparing two methods of oxygen delivery post extubation, the Venturi mask (n=52) and high-flow nasal oxygen (n=53), on the arterial oxygen tension to set inspired oxygen fraction ratio, in 105 patients with a PaO2/FiO2 ratio ≤300 mmHg immediately before extubation, and found:

  • 24 to 48 hours post extubation,
    • high-flow nasal oxygen was associated with
      • a higher PaO2/FiO2
        • 287±74 vs 247±81 at 24h, p=0.03
      • less
        • discomfort from
          • interface (2.6±2.2 vs 5.1±3.3 at 24h, p=0.006)
          • airway’s dryness (2.2±1.8 vs 3.7±2.4 at 24h, p=0.002).
        • interface displacement (32% vs 56%, p=0.01)
        • oxygen desaturation (40% vs 75%, p<0.001)
        • reintubation (4% vs 21%, p=0.01)
        • any form of ventilator support (7% vs 35%, p<0.001)

Conclusion:  Post extubation use of high-flow nasal oxygen, in comparison with venturi mask delivered oxygen, is associated with improved oxygenation, conmfort and outcomes.

Abstract:  Maurizio. Nasal High-flow vs Venturi Mask Oxygen Therapy After Extubation: Effects on Oxygenation, Comfort and Clinical Outcome. Am J Respir Crit Care Med 2014;epublished July 8th

Braunschweig and colleagues compared two intensities of nutrition - intensive medical nutrition therapy (n=40), the provision of >75% of estimated energy and protein needs per day via enteral nutrition and oral diet, and standard nutrition care (n=38), consisting of standard enteral nutrition and ad lib feeding - in 78 patients with acute lung injury, and found:

  • groups were similar at baseline
  • intensive medical nutrition therapy was associated with
    • a higher percentage delivery, per day of
      • estimated energy (84.7% vs 55.4%, p < 0.0001)
      • protein needs (76.1 vs 54.4%, p < 0.0001)
    • no statistical difference in
      • length of
        • mechanical ventilation
        • hospital stay
        • ICU stay
      • infections
    • increased mortality (40% vs 16%, p = 0.02)
      • hazard ratio 5.67 (p = 0.001)
      • necessitating premature cessation of the study

Conclusion:  The provision of >75% of estimated energy and protein, in comparison with standard nutritional therapy, is associated with increased mortality in patients with acute lung injury

Abstract:  Braunschweig. Intensive Nutrition in Acute Lung Injury. A Clinical Trial (INTACT). JPEN J Parenter Enteral Nutr;epublished April 9th

Azzopardi et al completed a long term assessment of the Total Body Hypothermia for Neonatal Encephalopathy Trial (TOBY), which compared standard care alone with standard care plus hypothermia to 33 to 34°C for 72 hours within 6 hours after birth, in 325 newborns with asphyxial encephalopathy born at a gestational age of ≥ 36 gestational weeks, and found at age 6 - 7 years:

  • hypothermia was associated with
    • an increase in
      • survival with an IQ score ≥ 85
        • 52% (75/145) vs 39% (52/132); relative risk 1.31; P=0.04
      • survival without neurological impairment
        • 45% (65/145) vs 28% (37/132); relative risk 1.60; 95% CI 1.15 to 2.22
    • reduced risk of
      • cerebral palsy (21% vs. 36%, P=0.03)
      • moderate or severe disability (22% vs. 37%, P=0.03)
    • no statistical significant difference in
      • mortality
        • hypothermia 29% vs control 30%
      • children's health status, based on
        • parental assessment
        • 10 of 11 psychometric tests

Conclusion: early hypothermia to 33 to 34°C for 72 hours after perinatal asphyxia resulted in improved neurocognitive outcomes in middle childhood.

Abstract:  Azzopardi. Effects of Hypothermia for Perinatal Asphyxia on Childhood Outcomes (TOBY Study) N Engl J Med 2014;371:140-149

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Interventional Study

Fu et al performed a 2-arm, evaluator-blinded, proof-of-concept study in 23 patients with primary supratentorial intracerebral haemorrhage with hematomal volume of 5 to 30 mL, evaluating fingolimod (a sphingosine 1–phosphate receptor modulator for multiple sclerosis, with potential for modulation of brain inflammation; n=11), 0.5 mg, orally for 3 consecutive days, and found:

  • fingolimod was associated with
    • by day 7
      • increased regainment of Glasgow Coma Scale score of 15 (100% vs 50%, p=0.01)
      • greater reduction of National Institutes of Health Stroke Scale score (7.5 vs 0.5, p < 0.001)
    • at 3 months
      • increased
        • full recovery of neurologic functions
          • modified Barthel Index score range: 95-100; 63% vs 0%; p = 0.001
          • modified Rankin Scale score range: 0-1; 63% vs 0%; p =0 .001
        • fewer reported ICH-related lung infections
    • decreased
      • perihematomal edema volume 
        • at day 7: 47 mL vs 108 mL; p = 0.04 
        • at day 14: 55 mL vs 124 mL; p = 0.07
    • increased
      • reductions in perihematomal edema volume
        • at day 14: 2.6 vs 7.7, p = 0.003
    • no differences in adverse events

Conclusion: In a small proof-of-concept study, oral fingolimod administered within 72 hours of intracerebral haemorrhage onset was safe, reduced perihaematoma oedema and neurologic deficits, and increased functional recovery.

Full Text:  Fu. Fingolimod for the Treatment of Intracerebral Hemorrhage:  A 2-Arm Proof-of-Concept Study. JAMA Neurol 2014;epublished July 7th

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Observational Studies

Zoller et al measured serum linezolid levels in 30 critically ill adult patients with suspected infections received standard dosing of 600 mg linezolid intravenously twice a day, and found:

  • a high variability of serum linezolid concentrations 
    • range of area under the linezolid concentration time curve over 24 hours (AUC24) 50.1 to 453.9 mg/L, median 143.3 mg*h/L;
    • range of trough concentrations (Cmin) < 0.13 to 14.49 mg/L, median 2.06 mg/L).
  • potentially subtherapeutic linezolid concentrations ( AUC24 < 200 mg*h/L and Cmin < 2 mg/L)
    • over 24 hours: 63%
    • at single time points: 50%
  • potentially toxic levels (AUC24 > 400 mg*h/L and Cmin > 10 mg/L) 
    • 7%

Conclusion: intensive care patients receiving standard doses of linezolid demonstrate high variability of serum linezolid concentrations

Full Text:  Zoller. Variability of linezolid concentrations after standard dosing in critically ill patients: a prospective observational study. Critical Care 2014;18:R148  

West et al performed a cross-sectional, retrospective, risk adjusted observational study examining whether workforce size (nurses, doctors and support staff) impacts the survival of critically ill patients (n=38,168) in ICU and in the hospital, and found:

  • reduced mortality was associated with
    • higher numbers of nurses per bed (odds ratio 0.90, 95% CI 0.83 to 0.97) 
    • higher numbers of consultants (odds ratio 0.85, 95% CI 0.76 to 0.95) 
  • the number of nurses had the greatest impact on patients at high risk of death (odds ratio 0.98, 95% CI 0.96 to 0.99)
  • the effect of medical staffing was unchanged across the range of patient acuity (odds ratio 1.00, 95% CI 0.97 to 1.03)
  • there was no relationship between patient outcomes and the number of support staff (administrative, clerical, technical and scientific staff) 
  • distinguishing between direct care and supernumerary nurses, and restricting the analysis to patients who had been in ICU for more than 8 h made little difference to the results
  • separate analysis of in-unit and in-hospital survival showed that the clinical workforce in intensive care had a greater impact on ICU mortality than on hospital mortality

Conclusion: in a retrospective analysis, levels of medical and nursing staffing is associated with the survival of critically ill patients

Full Text:  West. Nurse staffing, medical staffing and mortality in Intensive Care: An observational study. Int J Nurs Stud 2014;51(5):781-94

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Additional Studies

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Guidelines & Positional Statements

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Case Reports 


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Clinical Review Articles









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I hope you find these brief summaries and links useful.

Until next week