Newsletter 91 / September 1st 2013




Welcome to the 91st 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.

This week's research studies include interventional studies in pulmonary arterial hypertension, enteral feeding, PEEP and non-ST elevation acute coronary syndrome. Observational studies address brain death, post cardiac arrest prognostication, colloids, vitamin D in sepsis, mechanical ventilation, and the pulmonary artery catheter. Unfortunately, due to the time taken to write the ESC newsletter this morning, I have been unable to provide summaries for all the observational studies.

This week's guidelines focus on acute kidney injury, translaryngeal tracheostomy, COPD and H7N9 avian influenza. There are editorials on SARS, resistant microbes and idealism. Commentaries discuss medically-assisted death, medical records, medical relatives and the Affordable Care Act. There is a response to the Chappel commentary on colloids, recently published in the Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine.

Amongst the clinical review articles are papers on levetiracetam use in te critically ill, herat failure, mechanical circulatory assist devices, status asthmaticus, ARDS, SARS, blood purification, new oral anticoagulants, severe sepsis, new antimicrobials, and surgical fires. Non-clinical review articles include a series of six papers on scientific writing as well as an overview of reporting scientific studies.

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


Critical Care Reviews Meeting 2014

For the second year, Critical Care Reviews will be hosting a meeting discussing the major critical care studies published in the past 12 months. The first event was a small evening meeting attended by over 100 local clinicians. Paralleling the growth of the website, the 2014 meeting year will be significantly bigger, with talks from major international guest speakers Prof Alistair Nichol (Dublin/Melbourne), Prof Mervyn Singer (London) and Prof John Marshall (Toronto), in addition to a host of local intensivists, as well as colleagues from microbiology, haematology and hepatology. This all day event will finish with an informal evening question and answers session with the guest speakers, followed by dinner.

It's on Friday January 24th, just outside Belfast, so if you're a drive or short flight away, it would be great to have you come along. Travel on Thursday, attend the meeting on Friday and see some of the local landmarks over the weekend, before returning home on Sunday evening after a great winter break. On Saturday visit the North Coast: the World Heritage site Giants Causeway, Carrick-a-Rede rope bridge, Dunluce Castle and Bushmills Distillary, the oldest Distillary in the world; while on Sunday experience Belfast: the new acclaimed Titanic Centre followed by a famous black taxi tour describing the troubled past of one of Europe's now most vibrant cities. CPD approval will be sought from the UK Royal College of Anaesthetists. The full programme and registration will open in a few weeks. Please feel free to contact me if you're thinking on making the trip - it would be great to hear from you.



Randomized Controlled Trials

New England Journal of Medicine:     Pulmonary Arterial Hypertension

Pulido et al performed a randomized controlled trial in 742 patients with symptomatic pulmonary arterial hypertension, comparing macitentan, a dual endothelin-receptor antagonist, at doses of 3 mg once daily (n=250) or 10mg once daily (n=242), with placebo (n=250), and found:

  1. a dose dependent reduction in the occurance of the primary endpoint (time from the initiation of treatment to the first occurrence of a composite end point of death, atrial septostomy, lung transplantation, initiation of treatment with intravenous or subcutaneous prostanoids, or worsening of pulmonary arterial hypertension) with macitentan
    • hazard ratio for the 3-mg macitentan dose as compared with placebo 0.70 (97.5% CI 0.52 to 0.96; P=0.01)
    • hazard ratio for the 10-mg macitentan dose as compared with placebo 0.55 (97.5% CI 0.39 to 0.76; P<0.001)

Abstract:  Pulido. Macitentan and Morbidity and Mortality in Pulmonary Arterial Hypertension (SERAPHIN study). N Engl J Med 2013;369:809-818 


Critical Care Medicine:     Enteral Feeding

Heyland and colleagues performed a multi-centre, cluster randomized trial in 1,059 critically ill, mechanically ventilated patients, evaluating the effect of the enhanced protein-energy provision via an enteral route feeding protocol, combined with a nursing educational intervention on nutritional intake, compared to usual care, and found the intervention was associated with:

  1. increased proportion of prescribed protein and energy delivered by enteral nutrition
    • adjusted absolute mean difference between groups for protein increase was 14% (95% CI, 5-23%; p = 0.005)
    • adjusted absolute mean difference between groups for energy increase was 12% (95% CI, 5-20%; p = 0.004)
  2. there was no difference in average time from ICU admission to start of enteral nutrition (intervention sites 40.7-29.7 hr vs control sites 33.6-35.2 hr, p = 0.10)

Abstract:  Heyland. Enhanced Protein-Energy Provision via the Enteral Route Feeding Protocol in Critically Ill Patients: Results of a Cluster Randomized Trial. Crit Care Med 2013;epublished August 26th


Respiratory Care:     PEEP

Pintado and colleagues performed a pilot, randomized controlled trial in 70 patients with ARDS ventilated with low tidal volumes and limitation of airway pressure to 30 cm H2, and compared setting PEEP at either the highest compliance or based on FiO2, and found compliance-guided therapy was associated with:

  1. nonsignificant improvements in
    • PaO2/FiO2 at day 14
    • 28-day mortality (20.6% vs. 38.9%, p=0.12)
  2. significant improvements in
    • 28-day multiple-organ-dysfunction-free days (median 6 vs 20.5 d, p=0.02)
    • 28-day respiratory-failure-free days (median 7.5 vs 14.5 d, p=0.03)
    • 28-day hemodynamic-failure-free days (median 16 vs 22 d, p=0.04)

Full Text:  Pintado. Individualized PEEP Setting in Subjects With ARDS: A Randomized Controlled Pilot Study. Respir Care 2013 58:1416-1423


Journal of the American Medical Association:     Otamixaban in NSTE Coronary Syndromes

Steg and colleagues undertook an international, multi-centre, randomized, double-blind, active-controlled superiority trial in 13,229 patients with non-ST elevation acute coronary syndrome and a planned early invasive strategy, comparing otamixaban, a novel intravenous direct factor Xa inhibitor, with unfractionated heparin plus downstream eptifibatide, and found:

  1. no difference in the incidence of the primary efficacy outcome (a composite of all-cause death or new myocardial infarction at day 7); otamixaban 5.5% (279 of 5105 patients) versus unfractionated heparin plus eptifibatide 5.7% (310 of 5466 patients); adjusted relative risk 0.99; 95% CI 0.85-1.16; P =0 .93)
  2. no differences in secondary outcomes, including procedural thrombotic complications
  3. an increase with otamixaban therapy in the primary safety outcome of Thrombosis in Myocardial Infarction (TIMI) major or minor bleeding at day 7 (3.1% vs 1.5%; RR 2.13; 95% CI 1.63-2.78; P < 0.001)

nticoagulation With Otamixaban and Ischemic Events in Non–ST-Segment Elevation Acute Coronary SyndromesThe TAO Randomized Clinical Trial. JAMA 2013;epublished September 1st 


Observational Studies

Journal of Neurotrauma:     Brain Death

Egea-Guerrero et al completed a single-centre, prospective, observational study in 140 patients with severe traumatic brain injury TBI (GCS ≤ 8), evaluating the value of including acute S100B levels in standard clinical data as an early screening tool for brain death, and found:

  1. significantly higher S100B concentrations (p<0.001) in the 11.4% of patients who developed brain death
  2. multivariate analysis demonstrated significant odds ratios for
    • bilateral unresponsive mydriasis at admission (OR 21.35; p=0.005)
    • serum S100B at 24 h post-admission (OR 4.9; p=0.010)
  3. The AUC for 24 h S100B was 0.86; p=0.001; cut off 0.372 μg/L; 85.7% sensitivity, 79.3% specificity, positive predictive value 18.7%; negative predictive value 98.9%

Abstract:  Egea-Guerrero. S100B Protein May Detect Brain Death Development after Severe Traumatic Brain Injury. Journal of Neurotrauma 2013;epublished August 28th


Resuscitation:     Post Cardiac Arrest Prognostication

Green et al completed a single-centre, prospective, observational study, evaluating the importance of clinical signs in outcome prognostication in 200 patients post-cardiac arrest, and found:

  1. 9.9% of patients had a good outcome
  2. Over 8% of patients with absent or extensor motor response on day 3 achieved a good outcome
  3. 2 patients with myoclonic status epilepticus achieved a good outcome
  4. the odds of achieving a good outcome were lower in patients who suffered asystole (OR 0.187, 95% CI 0.039–0.875, p=0.033) compared with ventricular fibrillation or non-perfusing ventricular tachycardia, but some still achieved good outcome.
  5. the absence of pupillary and corneal reflexes on day 3 remained highly reliable for predicting poor outcome, regardless of therapeutic hypothermia utilization

Abstract:  Green. Clinical examination for prognostication in comatose cardiac arrest patients. Resuscitation 2013;epublished August 19th


Critical Care Medicine:     Colloids

Bayer and colleagues undertook a single-centre, prospective observational cohort study in 6,478 consecutive patients undergoing surgery with cardiopulmonary bypass to compare clinical outcomes of the synthetic colloids after cardiac surgery in a sequential manner

  • 2004-2006: tetrastarch (hydroxyethyl starch, predominantly 6% hydroxyethyl starch 130/0.4, n = 2,137)
  • 2006-2008: gelatin (4% gelatin in 2006-2008, n = 2,324) 
  • 2008-2010: only crystalloids (n = 2,017)

They found:

  1. renal replacement therapy was more common during periods when patients received synthetic colloids compared to only crystalloids.
  2. risk of renal replacement therapy was greater after both colloids, compared to crystalloids
    • hydroxyethyl starch: odds ratio 2.29; 95% CI 1.47-3.60; p < 0.001; using propensity analysis odds ratio 1.46; 95% CI 1.08, 1.97; p = 0.013
    • gelatin: odds ratio 2.75; 95% CI 1.84-4.16; p < 0.001; odds ratio 1.72; 95% CI 1.33 - 2.24; p < 0.001
  3. total fluid requirement was 163 mL/kg in the hydroxyethyl starch period, 207 mL/kg in the gelatin period, and 224 mL/kg in the crystalloid period.
  4. fluid intake was higher in the crystalloid group only during the first 20 hours.

Abstract:  Bayer. Perioperative Fluid Therapy With Tetrastarch and Gelatin in Cardiac Surgery-A Prospective Sequential Analysis. Crit Care Med 2013;epublished August 23rd


Critical Care Medicine:     Vitamin D & Sepsis

Abstract: Takuhiro. Association of Low Serum 25-Hydroxyvitamin D Levels and Sepsis in the Critically Ill. Crit Care Med 2013;epublished August 26th


Critical Care Medicine:     Mechanical Ventilation in Sepsis

Abstract:  Jay. Treatment With Neuromuscular Blocking Agents and the Risk of In-Hospital Mortality Among Mechanically Ventilated Patients With Severe Sepsis. Crit Care Med 2013;epublished August 26th


Critical Care Medicine:     Pulmonary Artery Catheter

Abstract:  Gershengorn. Understanding Changes in Established Practice: Pulmonary Artery Catheter Use in Critically Ill Patients. Crit Care Med 2013;epublished August 23rd




Journal of Thoracic Disease:     Severe acute respiratory syndrome   


Indian Journal of Critical Care Medicine:     Resistant Microbes


Journal of the Royal Medical Society:     Idealism



Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine:     Hydroxyethyl Starch



Journal of the American Medical Association:     Medical Records


Canadian Medical Association Journal:     Medically Assisted Death


New England Journal of Medicine:     Medical Relatives


Journal of Trauma and Acute Care Surgery:     Affordable Care Act


Review - Clinical


BioMed Research International:     Skeletal Muscle Oxygenation Saturation


Journal of Anaesthesiology Clinical Pharmacology:     Colloids in Traumatic Brain Injury


Frontiers in Neurology:     Levetiracetam



Journal of Thoracic Disease:     Percutaneous Coronary Intervention


Open Access Journal of Clinical Trials:     Atrial Fibrillation Anticoagulation


Circulation Research:     Heart Failure


Global Journal of Health Science:     Mechanical Circulatory Assist Devices


Journal of Thoracic Disease:     Acute Respiratory Distress Syndrome



European Respiratory Review:     Refractory Asthma


Biologics: Targets and Therapy:     Asthma Biomarkers



Chinese Medical Bulletin:     Blood Purification



Thrombsis & Haemostasis:     New Oral Anticoagulants



New England Journal of Medicine:     Severe Sepsis


Indian Journal of Critical Care Medicine:     Sepsis Induced Immunosuppression


International Journal of Applied and Basic Medical Research:     Procalcitonin


Virulence:     Endothelium in Sepsis


Annals of Clinical Microbiology and Antimicrobials:     New Antimicrobials



Clinical Cardiology:      Methamphetamine-Associated Cardiomyopathy



Archives of International Surgery:     Surgical Fires


Indian Journal of Critical Care Medicine:     Breaking Bad News


Review - Non-Clinical

Journal of Clinical Epidemiology:     Scientific Writing


PLoS Medicine:     Trial Reporting


I hope you find these brief summaries and links useful.

Until next week