Newsletter 117 / March 2nd 2014




Welcome to the 117th 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 dexmedetomidine during non-invasive ventilation, vasopressin and corticosteroids in septic shock, contrast-induced nephropathy and caspofungin prophylaxis; meta analyses address hydrocortisone for septic shock, delirium interventions in the critically ill, anti-TNFα therapy in sepsis and ICP monitoring in traumatic brain injury; while observational studies focus on stress ulcer prophylaxis plus lung recruitment in ARDS. There are also several other additional studies of interest.

There are two guidelines this week, including a multi-societal, and endorsed by ESICM, paper on hyponatraemia, as well as a Korean paper on influenza. One study critique looks at the TTM study, while editorials also address temperature management, consent to publish and medical reversal. Commentaries focus on influenza, tolvaptan, subcutaneous emphysema and testosterone. Amongst the clinical review articles are papers on sugammadex, stroke thrombolysis, intracranial hypertension, serelaxin, both cardiology and respiratory updates from 2013, contrast-induced nephropathy, micafungin, and metamphetamine abuse. One non-clinical review article discusses the role of revalidation in Australia.

The beginning of each month marks the addition of recently made open access articles from the major critical care journals, with the latest papers from the American Journal of Respiratory and Critical Care Medicine, Chest, Critical Care, Anesthesiology, Anesthesia & Analgesia, British Journal of Anaesthesia, Anaesthesia, and Anaesthesia and Intensive Care all added.

The topic for This Week's Papers is recreational drug toxicity, starting with a paper on opioid toxicity in tomorrow's Paper of the Day.


It's just two weeks to SMACCgold, the biggest critical care conference in the Southern Hemisphere. If you're coming along, there are a number of workshops the day before the main meeting starts, including one on Evidence-Based Medicine, being run by Simon Carley and Rick Body from Manchester, England, with me helping out. Simon and Rick have been busy, and have posted pre-course material on their excellent St. Emlyns blog. Check out Simon and Rick's other website, BestBETs, to learn how to perform a pragmatic appraisal of the evidence to answer a specific clinical question. If you want to improve your ability to appraise the literature, understand statisitcs and improve your journal club, then this is the workshop to attend. We're hoping each attendee will be able to produce an evidence-based appraisal that might just get published!  Of course, the day before the workshop is St Patricks Day, where SMACCgold becomes SMACCgreen - it promises to be fun. Follow on twitter (@critcarereviews) for the latest news and I'll tweet whatever is planned. I hope to see you on the Gold Coast, Queensland, Australia. Be sure to say hi.


Earlier this week I gave a Hot Topics talk at the National FFICM Preparation Course in London. Both references and slides of a collection of most know research papers and guidelines from 2013 and 2012 are available here.

Back to Top ↑



Randomized Controlled Trials

Devlin and colleagues completed a double blind, randomized, placebo-controlled trial, investigating the efficacy and safety of dexmedetomidine (n=16), in the presence of protocolized midazolam and fentanyl sedation, for non-invasive ventilation in 33 patients with early acute respiratory failure, and found:

  1. dexmedetomidine was associated with
    • no improvement in
      • NIV tolerance   (OR=1.44; 95% CI 0.44 to 4.70, p=0.54)
      • percentage time tolerating NIV  (dex: 99 hr (61-100) vs. placebo: 67 (40-100); p=0.56)
      • time at desired sedation level (SAS=3 or 4) (dex: 100 hr (86-100) vs. placebo: 100 (100-100); p=0.28)
      • avoidance of intubation
      • total duration of ventilation
      • severe bradycardia
      • hypotension
    • increased
      • duration of non-invasive ventilation

Abstract:  Devlin. Efficacy and Safety of Early Dexmedetomidine during Non-Invasive Ventilation for Patients with Acute Respiratory Failure: A Randomized, Double-Blind, Placebo-Controlled, Pilot Study. Chest 2014;epublished February 27th 

Gordon and colleagues undertook a multi-centre, open-label, randomized controlled pilot trial, in 61 patients with septic shock, evaluating the addition of IV hydrocortisone (50 mg 6 hourly, n=31) or placebo (n=30) to a vasopressin infusion (titrated up to 0.06 U/min), examining for an interaction between vasopressin and corticosteroids in septic shock, and found:

  1. hydrocortisone therapy was associated with a
    • shorter duration of vasopressin therapy (difference 3.1 d; 95% CI 1.1 to 5.1)
    • lower total dose of vasopressin (ratio 0.47; 95% CI 0.32 to 0.71)
  2. there was no difference in
    • plasma vasopressin levels (hydrocortisone group +64 pmol/L difference at 6- to 12-hour time point; 95% CI -32 to 160 pmol/L)
    • 28 day mortality rate (23% both groups)
    • organ failure
  3. vasopressin use was well tolerated 

Abstract:  Gordon. The Interaction of Vasopressin and Corticosteroids in Septic Shock: A Pilot Randomized Controlled Trial. Crit Care Med 2014;2014 February 19th

Kooiman and colleagues performed an noninferiority, open-label, multicentre randomized trial in 570 adults (intention-to-treat n=548) with chronic kidney disease, comparing 250 mL of 1.4% sodium bicarbonate hydration with 1000 mL of 0.9% saline hydration prior to intravenous contrast CT, and found:

  1. sodium bicarbonate therapy was associated with
    • a smaller relative increase in serum creatinine
      • 1.2% vs 1.5%; mean difference −0.3%; 95% CI −2.7 to 2.1, P-value for non-inferiority <0.0001
    • reduced hydration costs per patient
      • €224 versus €683; P < 0.001
  2. there was no difference in
    • contrast-induced acute kidney injury
      • sodium bicarbonate: n=8 (3.0%) versus saline: 14 (5.1%); P = 0.23
    • need for dialysis
      • n=0 both groups
    • renal recovery
      • sodium bicarbonate: 75% versus saline: 69%; P = 0.81
    • other healthcare costs

Abstract:  Kooiman. A randomized comparison of 1-h sodium bicarbonate hydration versus standard peri-procedural saline hydration in patients with chronic kidney disease undergoing intravenous contrast-enhanced computerized tomography. Nephrol Dial Transplant 2014;epublished February 27th   

Ostrosky-Zeichner and colleagues undertook a multicenter, randomized, double-blind, placebo-controlled trial of caspofungin as either pre-emptive or prophylactic antifungal therapy in 222 patients at risk for invasive candidiasis, and found:

  1. including patients with baseline disease
    • prophylactic caspofungin was associated with
      • no reduction in the incidence of proven/probable invasive candidiasis
        • placebo: 16.7% (14/84) versus caspofungin 9.8% (10/102); (P = 0.14)
    • pre-emptive caspofungin was associated with
      • reduced incidence of proven/probable invasive candidiasis
        • placebo: 30.4% (31/102) versus caspofungin 18.8% (22/117); (P = 0.04)
  2. there were no significant differences in secondary endpoints:
    • mortality
    • antifungal use
    • length of stay
    • safety

Abstract:  Ostrosky-Zeichner. A Randomized, Double-Blind, Placebo-Controlled Trial of Caspofungin Prophylaxis Followed by Preemptive Therapy for Invasive Candidiasis in High-Risk Adults in the Critical Care Setting. Clin Infect Dis 2014;epublished February 18th

Back to Top ↑

Meta Analysis

Wang et al pooled data from 8 randomized controlled trials, investigating the efficacy of low-dose hydrocortisone therapy in septic shock, and found:

  1. low-dose hydrocortisone therapy did not reduce 28-day mortality
    • n=1063; odds ratio  0.891, 95% CI 0.69 to 1.15
  2. low-dose hydrocortisone therapy ameliorated shock at
    • 7 days
      • 6 RCTs, n=964, OR 2.078, 95% CI 1.58 to 2.73, P < 0.0001,  I2 = 26.9%
    • 28 days
      • 6 RCTs, n=947, OR 1.495, 95% CI 1.12 to 1.99, P = 0.006, I2 = 0.0%

Abstract:  Wang. Low-Dose Hydrocortisone Therapy Attenuates Septic Shock in Adult Patients but Does Not Reduce 28-Day Mortality: A Meta-Analysis of Randomized Controlled Trials. Anesth Analg 2014;118(2):346–357

Al-Qadheeb reviewed data from 17 trials (n=2,849) examining whether interventions that are effective at reducing the duration of delirium are associated with a reduction in short-term mortality, and found:

  1. delirium duration was
    • lower in the intervention groups
      • difference 0.64 day; 95% CI -1.15 to -0.13; p = 0.01
    • reduced by ≥ 3 days in three studies
    • 0.1 to < 3 days in six studies
    • 0 day in seven studies
    • < 0 day in one study
  2. short-term mortality was not reduced in 13 studies reporting this outcome
    • risk ratio 0.90; 95% CI 0.76 to 1.06; p = 0.19
      • delirium duration was not associated with reduced short-term mortality (p = 0.11)
  3. the interventions studied were:
    • pharmacological studies (n=13)
      • dexmedetomidine, 6 studies
      • antipsychotics, 4 studies
      • rivastigmine, 2 studies
      • clonidine, 1 study
    • multimodal intervention
      • spontaneous awakening, 2 studies
    • nonpharmacologic intervention
      • early mobilization, 1 study
      • increased perfusion, 1 study

Abstract:  Al-Qadheeb. Randomized ICU Trials Do Not Demonstrate an Association Between Interventions That Reduce Delirium Duration and Short-Term Mortality: A Systematic Review and Meta-Analysis. Crit Care Med 2014;epublished February 19th  

Lv pooled data from 17 studies (n=8,971) comparing anti-TNF-α therapies with placebo in patients with severe sepsis or septic shock, and found:

  1. anti-TNF-α therapy was associated with
    • reductions in
      • 28-day all-cause mortality (OR = 0.91, 95% CI 0.83 to 0.99; p = 0.04)
      • including subgroups of anti-TNF-α antibodies (monoclonal and polyclonal) (OR 0.90, 95% CI 0.81 to 0.99; p = 0.04)
    • improved survival with
      • monoclonal antibodies (OR 0.91, 95% CI 0.82 to 1.00; p = 0.05)
    • no improved survival with
      • polyclonal antibodies (OR 0.71, 95% CI 0.39 to 1.28, p = 0.25)
      • receptor blockers (OR 0.95, 95% CI  0.78 to 1.17, p = 0.65)
  2. there was no publication bias or statistical heterogeneity; (I2 < 50%, p > 0.1)
  3. sensitivity analysis suggested results were highly stable

Abstract:  Lv. Anti-TNF-α therapy for patients with sepsis: a systematic meta-analysis. International Journal of Clinical Practice 2014;epublished February 18th

Su et al pooled data from two randomized controlled trials and seven cohort studies (n=11,038) investigating the efficacy and safety of intracranial pressure monitoring in patients with traumatic brain injury, and found:

  1. ICP monitoring was not associated with
    1. mortality reduction
      1. OR 1.16; 95% CI 0.87 to 1.54, I2 80%, P<0.00001
    2. unfavourable outcome
      1. OR 1.40; 95% CI 0.99 to 1.98; I2 = 4%, P = 0.35
    3. advese events
      1. OR 1.04; 95% CI, 0.64 to 1.70; I2 = 78%, P = 0.03

Full Text:  Su. The Effects of Intracranial Pressure Monitoring in Patients with Traumatic Brain Injury. PLoS ONE 2014;9(2):e87432

Back to Top ↑

Observational Studies

Wang and colleagues completed a large pharmacoepidemiological cohort study (71 hospitals, n=35,312) comparing histamine-2 receptor antagonists (n=13 439, 38.1%) with proton pump inhibitors (21 873, 61.9%) in adult patients requiring mechanical ventilation for ≥ 24 hours , and found:

  1. histamine-2 receptor antagonists were associated with less
    • gastrointestinal hemorrhage (2.1% vs 5.9%; P < 0.001)
    • pneumonia (27% vs 38.6%; P < 0.001)
    • Clostridium difficile infection (2.2% vs 3.8%; P < .001) 
  2. after adjusting for propensity score and covariates, histamine-2 receptor antagonists remained associated with less
    • GI hemorrhage (odds ratio 2.24; 95% CI, 1.81-2.76)
    • pneumonia (OR 1.2; 95% CI, 1.03-1.41)
    • Clostridium difficile infection (OR 1.29; 95% CI, 1.04-1.64)
  3. similar results were obtained in the propensity-matched models of 8,799 patients in each cohort
Abstract:  Wang. Histamine-2 Receptor Antagonists vs Proton Pump Inhibitors on Gastrointestinal Tract Hemorrhage and Maclaren. Infectious Complications in the Intensive Care Unit. JAMA Intern Med 2014;epublished February 17th

Liu and colleagues performed a prospective, single-center study investigating the efficacy of a lung recruitment maneuver (30 cmH2O for 60 seconds) with high-level positive end-expiratory pressure in 84 hypoxic (SpO2 < 88% for > 30 minutes) patients with 2009 influenza A (H1N1)-associated ARDS, and found:

  1. after the recruitment maneuver,
    • 40 patients (47.6%) had an increase (≥3%) in SpO2 (the responder group)
    • 44 patients (52.4%) had no increase (<3%) in SpO2 (the nonresponder group)
  2. SpO2 response was associated with
    • improved
      • mortality
        • 7/40 vs 18/ 44; P = 0.019
      • duration of mechanical ventilation (P = 0.011)
      • a lower initial PEEP level (P = 0.028)
      • higher initial dynamic lung-thorax compliance (P = 0.038)

Full Text:  Liu. Efficacy of Lung Recruitment Maneuver with High-Level Positive End-Expiratory Pressure in Patients with Influenza-Associated Acute Respiratory Distress: A Single-Center Prospective Study. Curr Ther Res Clin Exp 2013;75:83–87

Back to Top ↑

 Additional Studies


Back to Top ↑




Back to Top ↑


Clinical Review Articles









Back to Top ↑


Recently Made Open Access Articles from Major Journals

American Journal of Respiratory and Critical Care Medicine






Critical Care




Anesthesia & Analgesia


Anaesthesia & Intensive Care



Back to Top ↑


Non-Clinical Review Articles

Back to Top ↑



I hope you find these brief summaries and links useful.

Until next week