Newsletter 94 / September 22nd 2013




Welcome to the 94th 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 and guidelines from over 300 clinical and scientific journals. It's been a relatively quiet week for critical care publications, with no major interventional studies released in the past seven days, and only a small number of open access review articles being available.

This week's research studies include interventional trials investigating early physical therapy in ICU, gastric tube aspiration, high-flow nasal oxygen post extubation and frusemide administration as a renal stress test; meta analyses address the perioperative safety of hydroxyethyl starches, post-cardiac arrest prognostication, steroids for community-acquired pneumonia and the utility of the triple rule-out CT; observational trials examine medical harm in American hospitals, urinary NGAL, ECMO, sarcopaenia, brain injury and hypophosphataemia. From the Cochrane Collaboration, there are 8 new reviews, seven updated reviews and 2 editorials.

There is a guideline on nutritional support for the obese, plus two prehospital topics, spinal immobilsation and exercise-associated hyponatraemia. Editorials look at failings in healthcare systems, learning from errors and publishing, while two commentaries discuss conflict-of-interest and the pursuit of evidence.

Amongst the clinical review articles are papers on stroke, intra-aortic balloon counterpulsation, ARDS, contrast-induced nephropathy, cardiorenal syndrome, water-soluble vitamins and dialysis, serious hazards of transfusion, fondaparinux, guidelines and surgical risk assessment. Basic science reviews consider the blood-brain barrier and the physiology and pharmacology of the circulatory adrenergic system. Non-clinical reviews include articles on medical writing and Cochrane Reviews.

The topic for This Week's Papers is metabolic acidosis, starting with the first paper of a two part series in tomorrow's Paper of the Day.

If you only have time for one article this week, read Prof Rinaldo Bellomo's inspiring commentary about an event that shaped his career and led him to a lifetime of research and the pursuit of scientific knowedge. 


There are two meetings coming up that might be of interest to you:

Critical Care Reviews Meeting January 24th, 2014 - Belfast, Northern Ireland

  • If you are in Ireland or Great Britain (or a short flight away), Critical Care Reviews will be hosting it's second meeting outside Belfast, Northern Ireland. It's an all-day event with a fantastic programme consisting of local intensivists, local non-critical care specialists, and outstanding international guest speakers. Registration opens first week in October.

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. Registration is currently open.



Interventional Trials

PLoS One:     Physical Therapy

Camargo and colleagues report a case series of 19 haemodynamically stable and deeply sedated patients within the first 72 hrs of mechanical ventilation who underwent a single 20 minute passive leg cycling exercise using an electric cycle ergometer, and found:

  1. no clinically relevant changes in hemodynamic, respiratory or metabolic variables
    • cardiac output, systemic vascular resistance, central venous blood oxygen saturation, respiratory rate, tidal volume, oxygen consumption, carbon dioxide production or blood lactate
  2. just two minor adverse events unrelated to hemodynamic instability
  3. passive exercise may be considered safe, even in those requiring vasoactive agents (68%, with maximum concentration of noradrenaline 0.47 mcg/kg/min)

Full Text:  Camargo. Very early passive cycling exercise in mechanically ventilated critically ill patients: physiological and safety aspects - a case series. PLoS One. 2013 Sep 9;8(9):e74182


Journal of Parenteral and Enteral Nutrition:     Gastric Tube Aspiration

Williams et al undertook a randomized, controlled trial in 357 patients who stayed in ICU for >48 hours, had a gastric tube, and were likely to receive enteral nutrition for 3 or more days, comparing gastric tube aspirations every 4 hours (usual care, n=179) with a variable regimen (up to every 8 hours aspirations, n=179), and found the variable regimen was associated with:

  • fewer tube aspirations per day (3.4 versus 5.4, p < 0.001)
  • more vomiting/regurgitation (2.1% versus 3.6%, p = 0.02)
  • no other differences in complications
  • reductions in
    • nursing time,
    • risk of contamination of feeding circuit
    • risk of body fluid exposure

Abstract:  Williams. Frequency of Aspirating Gastric Tubes for Patients Receiving Enteral Nutrition in the ICU. A Randomized Controlled Trial. JPEN J Parenter Enteral Nutr 2013;epublished August 23rd


Respiratory Care:    Post Extubation Support

Rittayamai et al completed a single-centre, randomized cross-over study in 17 recently extubated subjects, comparing high-flow nasal cannulae for 30 min, followed by non-rebreathing mask for another 30 min (n=9), or the same two interventions, but applied in reverse order (n=8), and found high-flow nasal cannulae:

  1. were associated with reduced:
    • dyspnea (p = 0.04)
    • respiratory rate (p = 0.009)
    • heart rate (p = 0.006)
  2. most subjects (88.2%) preferred HFNC to non-rebreathing mask

Full Text:  Rittayamai. High-Flow Nasal Oxygen Cannula versus Conventional Oxygen Therapy After Endotracheal Extubation: A Randomized Cross Over Physiologic Study. Respir Care 2013;epublished September 17th


Critical Care:     Furosemide Stress Test

Chawla and colleagues examined the ability of a furosemide stress test (single dose of 1.0 or 1.5 mg/kg depending on prior furosemide-exposure) to predict the development of Acute Kidney Injury Network Stage-III in two cohorts of critically ill subjects with early AKI (cohort 1 was retrospective, n=23; cohort 2 was prospective, n=54), and found:

  1. 25 (32.4%) met the primary endpoint of progression to AKIN-III
  2. subjects with progressive AKI had significantly lower urine output following furosemide in each of the first 6 hours (p<0.001)
  3. The area under the receiver operator characteristic curves for the total urine output over the first 2 hours following furosemide to predict progression to AKIN-III was 0.87 (p = 0.001)
  4. The ideal-cutoff for predicting AKI progression during the first 2 hours following FST was a urine volume of less than 200mls (100ml/hr) with a sensitivity of 87.1% and specificity 84.1%

Full Text:  Chawla. Development and standardization of a furosemide stress test to predict the severity of acute kidney injury. Crit Care. 2013;17(5):R205


Meta Analysis

British Journal of Anaesthesia:     Hydroxyethyl Starches

Gillies and colleagues pooled data from 19 randomized studies comparing 6% HES solutions with alternative fluids in 1,657 patients undergoing surgery, and found no difference in:

  1. hospital mortality (risk difference 0.00, 95% CI −0.02, 0.02)
  2. requirement for renal replacement therapy (risk difference −0.01, 95% CI −0.04, 0.02)
  3. incidence of acute kidney injury (risk difference 0.02, 95% CI −0.02 to 0.06) between compared arms overall or in predefined subgroups

Abstract:  Gillies. Incidence of postoperative death and acute kidney injury associated with i.v. 6% hydroxyethyl starch use: systematic review and meta-analysis. Br J Anaesth 2013;epublished September 17th


Intensive Care Medicine:     Cardiac Arrest Prognostication

Kamps et al assessed the utility of outcome predictors in 1,153 patients (10 studies) treated with therapeutic hypothermia after CPR, and found at 72 hours post cardiac arrest:

  1. the motor response to painful stimuli and the corneal reflexes not to be a reliable tool for the early prediction of poor outcome
    • GCS motor score of 1–2 at 72 h false positive rate  0.21 (CI 0.08–0.43) (9 studies, n=811) 
    • bilaterally absent corneal reflexes at 72 h post cardiac arrest false positive rate 0.02 (CI 0.002–0.13) (n=429)
  2. pupillary response to light and the somatosensory evoked potential to be comparable to that in patients not treated with hypothermia
    • a bilaterally absent cortical N20 response of the somatosensory evoked potential false positive rate 0.007 (95% CI 0.001–0.047)  (9 studies, n=492)
    • bilaterally absent pupillary reflexes at 72 h post cardiac arrest false positive rate 0.004 (CI 0.001–0.03) (n=566)

Abstract:  Kamps. Prognostication of neurologic outcome in cardiac arrest patients after mild therapeutic hypothermia: a meta-analysis of the current literature. Intensive Care Med 2013;39(10):1671-1682


Respiratory Care:    Community-Acquired Pneumonia

Cheng and colleagues reviewed data from four trials, including 264 patients, evaluating the efficacy of corticosteroids in the treatment of severe community-acquired pneumonia, and found:

  1. corticosteroids significantly reduced hospital mortality compared with conventional therapy and placebo (Peto OR=0.39; 95% CI 0.17-0.90)
  2. the quality of the evidence underlying the pooled estimate of effect on hospital mortality was low, downgraded for inconsistency and imprecision

Full Text:  Cheng. Corticosteroid therapy for severe community-acquired pneumonia: A meta-analysis. Respir Care 2013;epublished September 17th


Academic Emergency Medicine:     Triple Rule-Out CT

Ayaram and colleagues pooled data from 11 studies (n=3,539; 791 triple rule-out and 2,748 non-triple rule-out) comparing the utility of the “triple rule-out” CT with other diagnostic modalities commonly used to evaluate patients with nontraumatic chest pain, and found:

  1. no significant difference in image quality between triple rule-out and dedicated CT scans
  2. triple rule-out CT had the following pooled diagnostic accuracy estimates for coronary artery disease:
    • sensitivity 94.3% (95% CI = 89.1% to 97.5%)
    • specificity 97.4% (95% CI = 96.1% to 98.4%)
    • positive likelihood ratio 17.71 (95% CI 3.92 to 79.96)
    • negative likelihood ratio 0.08 (95% CI 0.02 to 0.27)
  3. there were insufficient numbers of patients with PE or aortic dissection to generate diagnostic accuracy estimates for these conditions
  4. compared to non-triple rule-out CT scans, triple rule-out CT involved greater
    • radiation exposure (mean difference = 4.84 mSv, 95% CI 1.65 to 8.04 mSv) 
    • contrast exposure (mean difference = 38.0 mL, 95% CI 28.1 to 48.0 mL)

Abstract:  Ayaram. Triple Rule-out Computed Tomographic Angiography for Chest Pain: A Diagnostic Systematic Review and Meta-Analysis. Academic Emergency Medicine 2013;20:861–871


Observational Studies

Journal of Patient Safety:     Medical Harm

James and colleagues reviewed 4 limited studies that used the Global Trigger Tool to identify adverse patient events in medical records, to provide an updated estimate of patient harm associated with hospital care, and found:

  1. premature deaths associated with preventable harm to patients was estimated at more than 400,000 per year in the USA
    • a conservative estimate suggested 210,000 deaths per year
    • a 1984 estimate had suggetsed 98,000 Americans die each year from medical errors
  2. serious harm appears to be 10- to 20-fold more common than lethal harm

Full Text:  James. A New, Evidence-based Estimate of Patient Harms Associated with Hospital Care. J Patient Saf 2013;9:122Y128


Intensive Care Medicine:     Renal Biomarkers

Glassford and colleagues sought to explore the nature, source and discriminatory value of urinary NGAL in 102 ICU patients with SIRS  and oliguria, and/or a creatinine rise of >25 μmol/L, as a marker of acute kidney injury, and found:

  1. urinary NGAL not to be a useful predictor of AKI in this cohort
    • despite correlating well (r = 0.988), urinary NGAL and  monomeric urinary NGALE1 were clinically distinct, lacking both accuracy and precision (bias: 266.23; 95 % CI 82.03–450.44 ng/mg creatinine; limits of agreement: −1,573.86 to 2,106.32 ng/mg creatinine)
    • at best, urinary forms of NGAL were fair (AUC ≤0.799) predictors of renal or patient outcome
  2. uNGAL patterns may predict distinct clinical phenotypes
    • the 44 patients with a primarily monomeric source of urinary NGAL had higher plasma NGAL (118.5 ng/ml vs. 72.5 ng/ml; p < 0.001)
  3. The nature and source of uNGAL are complex and challenge the utility of NGAL as a uniform biomarker

Abstract:  Glassford. The nature and discriminatory value of urinary neutrophil gelatinase-associated lipocalin in critically ill patients at risk of acute kidney injury. Intensive Care Med 2013;39(10):1714-1724


Intensive Care Medicine:     Extracorporeal Membrane Oxygenation

In a multi-centre French study, in 140 ECMO-treated ARDS patients, Schmidt et al found:

  1. the main ARDS etiologies were bacterial (45 %), influenza A[H1N1] (26 %) and post-operative (17 %) pneumonias
  2. six month post-icu discharge survival to be 60%
  3. based on multivariable logistic regression analysis, the PRESERVE (PRedicting dEath for SEvere ARDS on VV-ECMO) score (0–14 points) was constructed with eight pre-ECMO parameters
    • age, body mass index, immunocompromised status, prone positioning, days of mechanical ventilation, sepsis-related organ failure assessment, plateau pressure andpositive end-expiratory pressure
    • six-month post-ECMO initiation cumulative probabilities of survival were (p < 0.001):
      • PRESERVE class 0–2:  97%
      • PRESERVE class 3–4:  79%
      • PRESERVE class 5–6:  54%
      • PRESERVE class ≥7:   16% 
  4. in 80 % of the 6-month survivors, there was satisfactory mental health but persistent physical and emotional-related difficulties, with anxiety (34%), depression (25%) and post-traumatic stress disorder (16%) common

Abstract:  Schmidt. The PRESERVE mortality risk score and analysis of long-term outcomes after extracorporeal membrane oxygenation for severe acute respiratory distress syndrome.  Intensive Care Med 2013;39(10):1704-1713


Critical Care:     Sarcopaenia in the Critically Ill

In a single-centre study, Moisey and colleagues examined 149 severely injured elderly (median age 79 years) trauma patients to determine if low skeletal muscle mass, calculated as muscle cross-sectional area at the 3rd lumbar vertebra on abdominal CT, was associated with adverse outcomes in this age group, and found:

  1. 71% were sarcopenic, of whom
    • 9% were underweight, 44% normal weight, and 47% overweight/obese
  2. overall mortality rate was 27%
    • univariate analysis demonstrated higher mortality among those who were sarcopenic (32% versus 14%, P = 0.018)
    • after controlling for age, sex, and injury severity, multiple logistic regression demonstrated increased muscle index was significantly associated with decreased mortality (OR per unit muscle index 0.93, 95% CI 0.875-0.997, P = 0.025). 
  3. sarcopenia, but not muscle index, was associated with decreased ventilator-free (P = 0.004) and ICU-free days (P = 0.002) on multivariate linear regression 
  4. neither BMI, serum albumin nor total adipose tissue on admission were indicative of survival, ventilator-free or ICU-free days

Full Text:  Moisey. Skeletal muscle predicts ventilator-free days, ICU-free days, and mortality in elderly ICU patients. Critical Care 2013;17:R206


Other observational studies of interest

Critical Care:     Hypophosphataemia

Full Text:  Yang. Hypophosphatemia during continuous veno-venous hemofiltration is associated with mortality in critically ill patients with acute kidney injury. Critical Care 2013;17:R205


Critical Care:     Brain Injury during Sepsis

Abstract:  Polito. Pattern of brain injury in the acute setting of human septic shock. Critical Care 2013;17:R204


Cochrane Reviews


Full Text:  Nicholson. Supraglottic airway devices versus tracheal intubation for airway management during general anaesthesia in obese patients. Cochrane Database of Systematic Reviews 2013, Issue 9. Art. No.: CD010105

Full Text:  Hurley. Aminophylline for bradyasystolic cardiac arrest in adults. Cochrane Database of Systematic Reviews 2013, Issue 8. Art. No.: CD006781

Full Text:  Gurusamy. Antibiotic prophylaxis for the prevention of methicillin-resistant Staphylococcus aureus (MRSA) related complications in surgical patients. Cochrane Database of Systematic Reviews 2013, Issue 8. Art. No.: CD010268

Full Text:  Gurusamy. Antibiotic therapy for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections in surgical wounds. Cochrane Database of Systematic Reviews 2013, Issue 8. Art. No.: CD009726

Full Text:  Bruins Slot. Factor Xa inhibitors versus vitamin K antagonists for preventing cerebral or systemic embolism in patients with atrial fibrillation. Cochrane Database of Systematic Reviews 2013, Issue 8. Art. No.: CD008980

Full Text:  Wikkelsø. Fibrinogen concentrate in bleeding patients. Cochrane Database of Systematic Reviews 2013, Issue 8. Art. No.: CD008864

Full Text:  Wakai. Nitrates for acute heart failure syndromes. Cochrane Database of Systematic Reviews 2013, Issue 8. Art. No.: CD005151

Full Text:  Shi. Oral hygiene care for critically ill patients to prevent ventilator-associated pneumonia. Cochrane Database of Systematic Reviews 2013, Issue 8. Art. No.: CD008367



Full Text:  Smith. Debridement for surgical wounds. Cochrane Database of Systematic Reviews 2013, Issue 9. Art. No.: CD006214

Full Text:  Cates. Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma. Cochrane Database of Systematic Reviews 2013, Issue 9. Art. No.: CD000052.

Full Text:  Alejandria. Intravenous immunoglobulin for treating sepsis, severe sepsis and septic shock. Cochrane Database of Systematic Reviews 2013, Issue 9. Art. No.: CD001090

Full Text:  Zacharias. Interventions for protecting renal function in the perioperative period. Cochrane Database of Systematic Reviews 2013, Issue 9. Art. No.: CD003590

Full Text:  Baharoglu. Antifibrinolytic therapy for aneurysmal subarachnoid haemorrhage. Cochrane Database of Systematic Reviews 2013, Issue 8. Art. No.: CD001245

Full Text:  Cabello. Oxygen therapy for acute myocardial infarction. Cochrane Database of Systematic Reviews 2013, Issue 8. Art. No.: CD007160

Full Text:  Hemilä. Vitamin C for preventing and treating pneumonia. Cochrane Database of Systematic Reviews 2013, Issue 8. Art. No.: CD005532





Wilderness & Environmental Medicine:     Exercise-Associated Hyponatraemia


Wilderness & Environmental Medicine:     Spinal Immobilization


Position Statement

Annals of Thoracic Medicine:     Quality & Safety in Critical Care


Postgraduate Medical Journal:     Healthcare Systems Failings


Anaesthesia:     Learning from Errors


Muller Journal of Medical Sciences and Research:     Publishing



Intensive Care Medicine:     Why We Practice Medicine

Canadian Medical Association Journal:     Conflict-of-Interest


Review - Clinical


Annals of Neurology:     Stroke Therapy


Annals of Neurology:     Stroke Imaging


Journal of Clinical Neuroscience:     Stroke Hemicraniectomy


Cerebrovascular Diseases:     Stroke Guidelines

Cerebrovascular Diseases:     Stroke-Associated Pneumonia



Clinical Cardiology:     Intra-Aortic Balloon Counterpulsation


Acta Anaesthesiologica Taiwanica:     Perioperative Statins


Cardiology:     Valvular Heart Disease


Frontiers in Physiology:     Atrial Fibrillation


Circulation:     Arrhythmogenic Right-Ventricular Cardiomyopathy



Jornal de Pediatria:     ARDS



Liver International:     Toll-Like Receptors 



ISRN Radiology:     Contrast-Induced Acute Kidney Injury


Cardiology:     Cardiorenal Syndrome


Seminars in Dialysis:     Water-Soluble Vitamins & Dialysis



Drug Design, Development and Therapy:     Fondaparinux


British Journal of Haematology:     SHOT



Digestive and Liver Disease:     Iron Deficiency Anaemia



International Journal of Science and Technology:     Adrenomedullin



Review - Basic Science

Frontiers in Physiology:     Cardiovascular Adrenergic System


Frontiers in Neuroengineering:     Blood-Brain Barrier


Review - Non-Clinical

PLoS Medicine:     Cochrane Reviews


Translational Research:     Medical Writing 

I hope you find these brief summaries and links useful.

Until next week