Newsletter 97 / October 13th 2013




Welcome to the 97th 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.

In news this week, the European Medicine's Agency Pharmacovigilance Risk Assessment Committee have modifed their position to ban hydroxythyl starches in all patient groups, now permiting it in the setting of  hypovolaemia caused by acute blood loss. Also, the poo pill takes a step closer to reality for the management for management of Clostridium difficile gut infection.

This week's research studies include randomised controlled trials investigating hypothermia for bacterial meningitis, albumin for ischaemic stroke, povidone-iodine oral decontamination for the prevention of ventilator-associated pneumonia and statin therapy for the prevention of contrast-induced nephropathy. Meta analyses examine peritoneal dialysis for acute kidney injury, endovascular therapy for ischaemic stroke and mechanical thrombectomy for acute myocardial infarction. Observational studies focus on the identification of central fever, perioperative morbidity associated with recent coronary stent placement, and a comparison of outcomes between dabigatran- and warfarin-associated major bleeding. The presentations from the ESICM hot topics session are now available online, including the OPTIMISE study, which I didn't have the results of on Wednesday.

There is one guideline this week, from the German Guideline Development Group, which looks at the management of nosocomial pneumonia, as well as a single editorial on research fraud.

Amongst the clinical review articles are papers on delirium, reperfusion, natriuretic peptides, haemodynamic monitoring, capnography, plethsmography, rectal trauma, TIPS, acute kidney injury biomarkers, hyperlactaemia, non-invasive haemoglobin monitoring, several articles on plasma-derived blood products and mannose-binding lectin. If you only have time to read one review paper, try "The Necessity for Clinical Reasoning in the Era of Evidence-Based Medicine", which comes with a couple of accompanying articles.

The topic for This Week's Papers is post cardiac arrest management, starting with a paper on therapy for post cardiac arrest syndrome in tomorrow's Paper of the Day.


There are three 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. The programme has been finalised and approved for 5 CPD points by the Royal College of Anaesthetists. Registration is now open. 

Intensive Care Society State-of-the-Art Meeting, December  16th - 18th, London

  • The ICS will be holding their annual State-of-the-Art meeting in London this December. It's the largest meeting of its kind in the UK and attracts a host of big names from the world of critical care.

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.



European Medicine's Agency:     Hydroxyethyl Starches  


Nature:     Clostridium Difficile



Interventional Trials

Unpublished:     OPTIMISE

Pearse and colleagues presented the results of the OPTIMISE trial at the hot topics session of the ESICM meeting earlier this week in Paris. This was a large multi-centre, randomized, controlled study comparing the intervention of  haemodynamic management using fluid and dopexamine based on a minimally invasive cardiac output monitor derived algorithm (n=367), with a control of standard therapy (n=367), in patients undergoing largely elective major gastrointestinal surgery, and found:

  1. the overall compliance rate in both groups was 91%
  2. regarding fluid therapy
    1. no apparent difference in administered volume (intervention 4190 ml versus control 4024 ml)
    2. the intervention group received more colloid (colloid therapy was part of the interventional protocol)
  3. trends for improvement
    • primary outcome
      • a composite of death and complications at 30 days (intervention 36.6% versus control 44.4%; RR 0.84, 95% CI 0.71 - 1.01; p=0.07)
    • secondary outcomes
      • death at 180 days (intervention 7.7% versus 11.6%; RR 0.66, 95% CI 0.42 - 1.05, P=0.079)
      • infection (23.8% versus 29.7%; RR 0.80, 95% CI 0.63 - 1.02, P=0.079) 
  4. no difference in hospital stay (10 versus 11 days; P=0.054)


Journal of the American Medical Association:     Bacterial Meningitis

Mourvillier and colleagues performed an open-label, multicenter, randomized clinical trial in France, comparing therapeutic hypothermia (32°C to 34°C for 48 hours, n=49) followed by passive rewarming, with standard care (n=49) in comatose adults with community-acquired bacterial meningitis, and found:

  1. the trail was stopped early due to excess deaths associated with hypothermia  (51% versus 31%; RR 1.99; 95% CI 1.05-3.77; P =0 .04)
  2. 77% of patients had pneumococcal meningitis
  3. mean (SD) temperatures at 24 hours after randomization were
    • hypothermia: 33.3°C (0.9°C)
    • standard therapy: 37.0°C (0.9°C) 
  4. at 3 months, there was a non-significant increase in unfavourable outcome with hypothermia (86% versus 74%; RR 2.17; 95% CI 0.78-6.01; P = 0.13)
  5. adjusted mortality was non-significantly higher (hazard ratio 1.76; 95% CI 0.89-3.45; P = 0.10).

Full Text:  Mourvillier. Induced Hypothermia in Severe Bacterial Meningitis:  A Randomized Clinical Trial. JAMA 2013;epublished October 8th


Lancet Neurology:     Stroke

Ginsberg and colleagues completed an international, multi-centre, randomised, double-blind, parallel-group, phase 3, placebo-controlled trial, comparing 25% albumin (2 g [8 mL] per kg; maximum dose 750 mL, n=422) with the equivalent volume of isotonic saline (n=419) in patients with ischaemic stroke, a baseline National Institutes of Health stroke scale score of 6 or more treated within 5 h of onset, and found:
  1. the trial was stopped early for futility
  2. there was no difference in rates of the adjusted primary outcome of favourable outcome at 90 days (albumin 44% versus control 44%; risk ratio 0·96; 95% CI 0·84—1·10)
  3. albumin therapy was associated with increased rates of
    • mild-to-moderate pulmonary oedema (13% versus 1%);
    • symptomatic intracranial haemorrhage within 24 h (4% versus 2%)
  4. the rate of favourable outcome in patients given albumin remained consistent at 44—45% over the course of the trial, while the cumulative rate of favourable outcome in patients given saline rose from 31% to 44%

Abstract:  Ginsberg. High-dose albumin treatment for acute ischaemic stroke (ALIAS) part 2: a randomised, double-blind, phase 3, placebo-controlled trial. Lancet Neurology 2013;epublished September 27th


Critical Care Medicine:     Ventilator-Associated Pneumonia

Seguin and colleagues undertook a multicenter, placebo-controlled, randomized, double-blind, two-parallel-group trial comparing oropharyngeal care with povidone-iodine (n = 91) with placebo (n = 88) six times daily in patients with severe brain injury or haemorrhagic stroke expected to be mechanically ventilated for more than 24 hours, and found:

  1. no difference in the rate of VAP (povidone-iodine 31% versus placebo 28%; RR 1.11; 95% CI 0.67-1.82; p = 0.69)
  2. no significant difference between the two groups for ventilator-associated tracheobronchitis (povidone-iodine 10% versus placebo 7%; RR 1.48; 95% CI 0.51-4.31; p = 0.47)
  3. a trend for increased incidence of ARDS with povidone-iodine therapy (5 versus 0 patients; p= 0.06) 
  4. no difference in
    • ICU length of stay
    • hospital length of stay
    • ICU mortality 
    • 90-day mortality

Abstract:  Seguin. Effect of Oropharyngeal Povidone-Iodine Preventive Oral Care on Ventilator-Associated Pneumonia in Severely Brain-Injured or Cerebral Hemorrhage Patients: A Multicenter, Randomized Controlled Trial (SPIRIT study). Crit Care Review 2013;epublished October 7th


Journal of the American College of Cardiology:     Contrast-Induced Nephropathy

Leoncini and colleagues performed a randomised trial in 504 consecutive statin-naïve patients with non-ST elevation acute coronary syndrome scheduled for early invasive strategy, comparing rosuvastatin (40 mg on-admission following by 20 mg/day, n=252) with no statin (n=252), and found:

  1. statin therapy was associated with
    • a decreased incidence of contrast-induced acute kidney injury (6.7 vs 15.1%; adjusted odds ratio 0.38; 95% CI 0.20-0.71; p= 0.003)
    • a decreased 30-day incidence of adverse cardiovascular and renal events (3.6% versus 7.9 %; p = 0.036)
  2. on-admission statin treatment was associated with a trend for lower rates of death or non fatal myocardial infarction at 6-months (3.6% vs 7.2%, p = 0.07)

Abstract:  Leoncini. Early high-dose rosuvastatin for Contrast-Induced Nephropathy Prevention in Acute Coronary Syndrome. Results from Protective effect of Rosuvastatin and Antiplatelet Therapy On contrast-induced acute kidney injury and myocardial damage in patients with Acute Coronary Syndrome (PRATO-ACS Study). J Am Coll Cardiol 2013;epublished October 9th


Meta Analysis

Clinical Journal of the American Journal of Society of Nephrology:     Peritoneal Dialysis

Chionh and colleagues compared peritoneal dialysis with extracorporeal blood purification (continuous or intermittent hemodialysis) for the treatment of acute kidney injury, and found:

  1. the pooled mortality of AKI treated with PD only was 39.3% (13 studies, n=597) 
  2. in 11 comparative studies, there was no difference in mortalty between PD (58.0%, n=392) and extracorporeal blood purification (56.1%, n=567)
    • in 7 cohort studies, there was no difference in mortality (odds ratio 0.96; 95% CI 0.53 to 1.71)
    • in 4 randomized trials, there was no difference in mortality (odds ratio 1.50; 95% confidence interval 0.46 to 4.86; heterogeneity was significant I2=73%, P=0.03)
  3. overall methodological quality was low

Abstract:  Chionh. Use of Peritoneal Dialysis in AKI: A Systematic Review. CJASN October 2013;8(10):1649-1660


Mayo Clinic Clinic Proceedings:     Ischaemic Stroke

Singh and colleagues pooled data from 5 randomized controlled trials (n=1,197) comparing endovascular therapy (n=711) with intravenous tissue plasminogen activator for the management of ischaemic stroke (n=486), and found:

  1. no significant improvement with endovascular therapy compared with IV thrombolysis
  2. on subgroup analysis,
    • endovascular therapy was associated with improved outcomes in patients with severe stroke (National Institutes of Health Stroke Scale score ≥20),
    • a dose-response gradient was evident, improving excellent, good, and fair outcomes by an additional 4%, 7%, and 13%, respectively

Full Text:  Singh. Endovascular Therapy for Acute Ischemic Stroke: A Systematic Review and Meta-analysis. Mayo Clin Proc 2013;88(10):1056-1065


Journal of the American College of Cardiology:     Mechanical Thrombectomy

Kumbhani and colleagues compared aspiration thrombectomy or mechanical thrombectomy before primary percutaneous coronary intervention, with conventional primary PCI alone for the management of acute myocardial infarction, and found:

  1. aspiration thrombectomy, compared with conventional primary PCI (18 trials, n=3,936)
    • was associated with improvements in
      • major adverse cardiac events (RR 0.76; 95% CI 0.63 - 0.92; p = 0.006)
      • all-cause mortality (RR 0.71; 95% CI 0.51 - 0.99; p = 0.049)
      • ST-segment resolution at 60 min (RR: 1.31; 95% CI: 1.16 to 1.48; p < 0.0001) 
      • Thrombolysis In Myocardial Infarction blush grade (TBG) 3 post-procedure (RR: 1.37; 95% CI: 1.19 to 1.59; p < 0.0001)
    • with trends for improvement in
      • recurrent MI (p = 0.11)
      • target vessel revascularization (p = 0.06)
    • no difference in
      • final infarct size (p = 0.64) 
      • ejection fraction (p = 0.32) at 1 month
  2. Mechanical thrombectomy vs. conventional primary PCI (7 trials, n = 1,598), was associated with
    • no difference in major adverse cardiac events (RR 1.10; 95% CI 0.59 to 2.05; p = 0.77)
    • mortality (p = 0.57)
    • recurrent MI (p = 0.32)
    • target vessel revascularization (p = 0.19)
    • final infarct size (p = 0.47)

Abstract:  Kumbhani. Role of Aspiration and Mechanical Thrombectomy in Patients With Acute Myocardial Infarction Undergoing Primary Angioplasty. An Updated Meta-Analysis of Randomized Trials. J Am Coll Cardiol 2013;62(16):1409-1418


Observational Studies

JAMA Neurology:     Central Fever

Hocker and colleagues completed a single-centre, retrospective study in 526 patients aiming to develop a model to differentiate central from infectious fever in critically ill neurologic patients with fever of an undetermined cause, and found:

  1. fever was central in 46.8%
  2. infectious fever was associated with:
    • older patients (mean 57.4 vs 53.5 years; P =0.01)
    • longer stay in intensive care unit (mean 12.1 versus 8.8 days; P  < 0.001)
  3. central fever was associated with
    • occurance within 72 hours of admission to neuro ICU (76.4% versus 60.7%; P < 0.001)
    • lasting longer than 6 hours for 2 or more consecutive days (26.4% vs 18.6%; P  = 0.04).
  4. using multivariable analysis, independent predictors of central fever were
    • blood transfusion (OR 3.06; 95% CI 1.63-5.76)
    • absence of infiltrate on chest x-ray (OR 3.02; 95% CI 1.81-5.05)
    • diagnosis of subarachnoid hemorrhage, intraventricular hemorrhage, or tumor (OR 6.33; 95% CI 3.72-10.77)
    • onset of fever within 72 hours of hospital admission (OR 2.20; 95% CI 1.23-3.94)
  5. central fever coud be predicted with a probability of 0.90 using the combination of
    • negative cultures
    • absence of infiltrate on chest radiograph
    • diagnosis of subarachnoid hemorrhage, intraventricular hemorrhage, or tumor
    • onset of fever within 72 hours of admission 

Abstract:  Hocker. Indicators of Central Fever in the Neurologic Intensive Care Unit. JAMA 2013;epublished October 7th   


Journal of the American Medical Association:     Coronary Stents & Surgery

Hawn and colleagues completed a national retrospective cohort study examining the association between interval between coronary stent placement and major cardiac complications post surgery in 41 989 Veterans Affairs (VA) and non-VA operations occurring in the 24 months after a coronary stent implantation, and found:

  1. within 24 months of 124,844 coronary stent implantations (47.6% drug eluting, 52.4% base metal), 28,029 patients (22.5%; 95% CI 22.2%-22.7%) underwent noncardiac operations resulting in 1,980 major adverse cardiac events (4.7%; 95% CI 4.5%-4.9%).
  2. time between stent and surgery was associated with major adverse cardiac events
    • <6 weeks: 11.6%;
    • 6 weeks to <6 months: 6.4%
    • 6-12 months: 4.2%;
    • >12-24 months: 3.5%; P < 0.001)
  3. major adverse cardiac events were more common with bare metal stents than drug eluting stents (5.1% versus 4.3%; P<0.001)
  4. after adjustment, the 3 factors most strongly associated with major adverse cardiac events were
    • nonelective surgical admission (adjusted odds ratio 4.77; 95% CI 4.07-5.59)
    • history of myocardial infarction in the 6 months preceding surgery (AOR 2.63; 95% CI 2.32-2.98)
    • revised cardiac risk index greater than 2 (AOR 2.13; 95% CI 1.85-2.44)
  5. of 12 variables in the model, timing of surgery ranked fifth in explanatory importance
  6. stent type ranked last, and DES was not significantly associated with major adverse cardiac events (AOR 0.91; 95% CI 0.83-1.01)
  7. after both BMS and DES placement, the risk of major adverse cardiac events was stable at 6 months.
  8. a case-control analysis of 284 matched pairs found no association between antiplatelet cessation and major adverse cardiac events (OR 0.86; 95% CI 0.57-1.29)

Full Text:  Hawn. Risk of Major Adverse Cardiac Events Following Noncardiac Surgery in Patients With Coronary Stents. JAMA 2013;epublished October 7th


Circulation:     Anticoagulant-Related Bleeding

Majeed and colleagues compared the management and prognosis of major bleeding in patients treated with dabigatran or warfarin, by evaluating bleeding reports from 5 phase III trials comparing dabigatran with warfarin in 27,419 patients treated for 6 to 36 months, and found:

  1. there were 1,121 major bleeds in 1,034 individuals
    • dabigatran (3.7%; 627/16,755) versus warfarin (4.1%; 407/10,002)
  2. patients with major bleeds on dabigatran, in comparison with major bleeds on warfarin,
    • were older
    • had lower creatinine clearance 
    • frequently also used aspirin or non-steroid anti-inflammatory agents
  3. a first major bleed on dabigatran, rather than warfarin, was associated with a trend for a lower 30-day mortality (9.1% versus 13.0%; OR 0.68, 95% CI 0.46-1.01; p=0.057) (adjusted OR 0.66; 95% CI 0.44-1.00; p=0.051)
  4. patients on dabigatran with major bleeds received
    • more blood transfusion (61% versus 42%; p<0.001)
    • less plasma transfusion (19.8% versus 30.2%; p<0.001)

Abstract:  Majeed. Management and Outcomes of Major Bleeding during Treatment with Dabigatran or Warfarin. Circulation 2013;epublished September 30th  


Other studies of interest

Respiratory Care:     Chest Physiotherapy

Full Text:  Guimarães. Expiratory Rib Cage Compression, Secretion Clearance and Respiratory Mechanics in Mechanically Ventilated Patients: A Randomized Crossover Trial. Respir Care 2013;epublished October 8th


Critical Care:     Red Cell Transfusion

Full Text:  Kaukonen. Age of red blood cells and outcome in acute kidney injury. Crit Care 2013;17(5):R222


Journal of Neurotrauma:     Intracranial Pressure Monitoring

Abstract:  Aziz. Intracranial Pressure Monitoring in Severe Traumatic Brain Injury: Results from the American College of Surgeons Trauma Quality Improvement Program.  J Neurotrauma 2013;30(20):1737-1746


PLoS Biology:     Assessment of Scientific Worth

Full Text:  Eyre-Walker. The Assessment of Science: The Relative Merits of Post-Publication Review, the Impact Factor, and the Number of Citations. PLoS Biol 2013;11(10):e1001675