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Critical Care Reviews Newsletter

June 9th 2013



Welcome to the 79th 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 a huge newsletter this week, containing 103 articles.

This week's research studies include investigations into high volume haemofiltration in sepsis, early surgery for intracerebral haemorrhage, blood pressure control post stroke, pneumatic compression devices in immoblie stroke patients, the worldwide incidence of acute kidney injury and the burden of central venous catheter-associated bloodstream infections in the USA. There are numerous Cochrane reviews, including meta analyses on PEEP, impregnated central lines, wound infection in burns, bacterial meningitis and cardiogenic pulmonary oedema.

This week's guidelines address abdominal compartment syndrome, heart failure and stroke. There is one editiorial on guidelines and commentaries on starches, kidney diseases and fructose.

Amongst the clinical review articles are papers on right ventricular infarction, lung protective ventilation, the difficult airway, chest radiograph interpretation, acute pancreatitis, interpretation of liver function tests, cirrhosis, traumatic coagulopathy, carnitine in sepsis and cadmium toxicity. The latest review articles from the major journal that are now open access are also included.

The topic for This Week's Papers is principles of antibacterial therapy, starting with a paper on antibiotic resistance in the ICU in tomorrow's Paper of the Day.



Intensive Care Medicine:     Renal Replacement Therapy

Joannes-Boyau and colleagues undertook a multicentre randomized controlled trial in 140 (137 analyzed) crtically ill patients with septic shock comparing high-volume haemofiltration (HVHF, n=66) at 70 mL/kg/h with standard-volume haemofiltration (SVHF, n=71) at 35 mL/kg/h, for a 96-h period. The trial was stopped early due to slow patient accrual and resource limitations. There was no difference in the primary end-point of 28-day mortality (HVHF 37.9 % vs. SVHF 40.8 %, p = 0.94) or in secondary endpoints.

Abstract:  Joannes-Boyau. High-volume versus standard-volume haemofiltration for septic shock patients with acute kidney injury (IVOIRE study): a multicentre randomized controlled trial. Intensive Care Med 2013;epublished June 6th


Intensive Care Medicine:     Dobutamine in Sepsis

Hernandez et al performed a randomized, controlled, double-blind, crossover study to evaluate the effects of dobutamine on hemodynamic, metabolic, peripheral, hepatosplanchnic and microcirculatory perfusion parameters during early septic shock resuscitation. 20 septic shock patients with cardiac index ≥2.5 l/min/m2and hyperlactatemia received dobutamine (5 mcg/kg/min fixed-dose) or placebo. Although dobutamine increased cardiac index, heart rate and left ventricular ejection fraction, it did not improve tissue perfusion or function in the investigated regional circulations.  

Abstract:  Hernandez. Effects of dobutamine on systemic, regional and microcirculatory perfusion parameters in septic shock: a randomized, placebo-controlled, double-blind, crossover study. Intensve Care Med 2013;epublished June 6th


Clinical Journal of the American Society of Nephrology:     Acute Kidney Injury

Susantitaphong and colleagues completed a systematic review (2004–2012) of large cohort studies from 2004 to 2012 to estimate the world incidence of AKI and its stages of severity and associated mortality. In 154 studies (n=3,585,911) using a KDIGO-equivalent AKI definition, the pooled incidence rates of AKI were 21.6% in adults (95% CI 19.3 to 24.1) and 33.7% in children (95% CI 26.9 to 41.3). The pooled AKI-associated mortality rates were 23.9% in adults (95% CI 22.1 to 25.7) and 13.8% in children (95% CI 8.8 to 21.0). The AKI-associated mortality rate declined over time, and was inversely related to income of countries and percentage of gross domestic product spent on total health expenditure.

Abstract: Susantitaphong. World Incidence of AKI: A Meta-Analysis. Clin J Am Soc Nephrol 2013; epublished June 6th


Lancet:     Intracerebral Haemorrhage

Mendelow et al completed an international, multi-centre, parallel-group trial comparing early surgery (n=307) with conservative therapy (n=294) in conscious patients with superficial lobar intracerebral haemorrhage of 10—100 mL and no intraventricular haemorrhage. There was no difference in the primary outcome of rates of unfavourable outcome at 6 months (surgery 59% versus 62%; odds ratio 0·86, 0·62 to 1·20; p=0·367). There was no difference in 6 mortality (surgery 18% versus conservative therapy 24%; OR 0·71, 95% CI 0·48 to 1·06; p=0·095).

Full Text:  Mendelow. Early surgery versus initial conservative treatment in patients with spontaneous supratentorial lobar intracerebral haematomas (STICH II): a randomised trial. Lancet 2013;epublished May 29th   (free registration required)


Lancet:     Stroke

The SPS3 study investigators completed a two-by-two multifactorial, randomised open-label trial examining the effects of different blood-pressure targets on the rate of recurrent stroke in 3020 patients with recent lacunar stroke.  1519 patients were randomized to a higher blood pressure target group (130—149 mm Hg) and 1501 to a lower-target group (<130 mm Hg), with a mean follow up of 3·7 years.  After 1 year, mean systolic blood pressure was 138 mm Hg (95% CI 137—139) in the higher-target group and 127 mm Hg (95% CI 126—128) in the lower-target group. The lower blood pressure target was associated with a reduced rate of intracerebral haemorrhage (0·37, 0·15—0·95, p=0·03), a trend for reduced total stroke (hazard ratio 0·81, 95% CI 0·64—1·03, p=0·08), but no difference  in disabling or fatal stroke (0·81, 0·53—1·23, p=0·32), and the composite outcome of myocardial infarction or vascular death (0·84, 0·68—1·04, p=0·32). Treatment-related serious adverse events were infrequent.

Abstract:  The SPS3 Study Group. Blood-pressure targets in patients with recent lacunar stroke: the SPS3 randomised trial. Lancet 2013;epublished May 28


Lancet:     Venothromboembolism

The CLOTS investigators performed a a multicentre parallel group randomised trial investigating the effectiveness of intermittent pneumatic compression (IPC) to reduce the risk of DVT in 2876 immobile stroke patients. IPC (n=1438) reduced DVT in comparison with no IPC (n=1438), (8.5% versus 12.1%, absolute reduction in risk 3·6%, 95% CI 1·4—5·8; adjusted odds ratio 0·65, 95% CI 0·51—0·84; p=0·001). There was a trend towards decreased 30 day mortality with IPC therapy (11% versus 13%, p=0·057). IPC use was associated with increased incidence of leg skin breaks 3% versus 1%, p=0.002), but not falls with injury (2% versus 2%, p=0.221).

Full Text:  CLOTS (Clots in Legs Or sTockings after Stroke) Trials Collaboration. Effectiveness of intermittent pneumatic compression in reduction of risk of deep vein thrombosis in patients who have had a stroke (CLOTS 3): a multicentre randomised controlled trial. Lancet 2013;epublished May 31st


Lancet Respiratory Medicine:     Magnesium for Asthma

Powell et al undertook a randomised placebo-controlled, multi-centre, parallel trial to assess the effect of 250 mmol nebulized MgSO4 in 508 children aged 2-16 with acute severe acute asthma not responding to standard inhaled therapy. The primary endpoint of mean Yung Asthma Severity Score at 60 min was lower in the MgSO4 group (4·72 [SD 1·37] versus 4·95 [SD 1·40]; adjusted difference −0·25, 95% CI −0·48 to −0·02; p=0·03), an effect which was clinically insignificant. The clinical effect was larger in children with more severe asthma exacerbation (p=0·03) and those with symptoms present for less than 6 h (p=0·049). There was no difference in adverse events between groups.

Abstract:  Powell. Magnesium sulphate in acute severe asthma in children (MAGNETIC): a randomised, placebo-controlled trial. Lancet Respir Med 2013;1(4):301-308


British Medical Journal:     Influenza

In a double blind randomized trial in 326 patients with severe influenza (75.5% children aged <15), comparing oral oseltamivir at double dose (150 mg twice a day/paediatric equivalent, n=165) with standard dose (75 mg twice a day/paediatric equivalent, n=161), double dose therapy was not associated with improvements in mortality (double dose: 7.3% versus standard dose: 5.6%), days of supplemental oxygen, duration of mechanical ventilation (DD: 2.5 days (1-16) versus SD: 8 days (1-16)) or duration of intensive care admission (DD: 4.5 days (3-6) versus SD: 5 days (2-11). Tolerability of doses were similar.

Full Text:  South East Asia Infectious Disease Clinical Research Network. Effect of double dose oseltamivir on clinical and virological outcomes in children and adults admitted to hospital with severe influenza: double blind randomised controlled trial. BMJ 2013; 346: f3039


Infection Control and Hospital Epidemiology:     Central Venous Catheter-Associated Bacteraemia

Using Monte Carlo simulation based on data from nearly all US hospitals, Wise and colleagues estimated that there were between 462,000 and 636,000 central line-associated blood stream infections (CLABSIs) in nonneonatal critical care patients in the United States during 1990–2010. CLABSI rate reductions led to between 104,000 and 198,000 fewer CLABSIs than would have occurred if rates had remained unchanged since 1990. There were 15,000 hospital-onset CLABSIs in nonneonatal critical care patients in 2010; 70% occurred in medium and large teaching hospitals.

Full Text:   Wise. National Estimates of Central Line–Associated Bloodstream Infections in Critical Care Patients. Infect Control Hosp Epidemiol 2013;34(6):547-554


Cochrane Reviews

Cochrane Review:     PEEP

Santa Cruz performed a systematic review and meta analysis to assess the benefits and harms of high versus low levels of PEEP in patients with ARDS and acute lung injury. Seven studies (n=2565) were included, although not all studies met eligibility criteria for each analyses. In three studies assessing in-hospital mortality, and comparing high versus low PEEP with the same tidal volume, there was no difference in mortality, risk of barotrauma (RR 0.97, 95% CI 0.66 to 1.42), or number of ventilator-free days. High-PEEP was associated with improved oxygenation, and possibly decreased mortality in the ARDS subgroup, although study designs limit this conclusion. 

Full Text:  Santa Cruz. High versus low positive end-expiratory pressure (PEEP) levels for mechanically ventilated adult patients with acute lung injury and acute respiratory distress syndrome. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD009098


Cochrane Review:     Central Venous Catheter Impregnation

Lai evaluated the effects of antimicrobial CVCs in reducing clinically diagnosed sepsis, established catheter-related bloodstream infection (CRBSI) and mortality. 56 studies with 16,512 catheters and 11 types of antimicrobial impregnations were analysed. Catheter impregnation significantly reduced CRBSI, with an absolute risk reduction of 2% (95% CI 3% to 1%), risk ratio of 0.61 (95% CI 0.51 to 0.73) and number needed to treat of 50. Catheter impregnation also reduced catheter colonization, with an absolute risk reduction of 10% (95% CI 13% to 7%), RR of 0.66 (95% CI 0.58 to 0.75) and NNT of 10. However, catheter impregnation made no significant difference to the rates of clinically diagnosed sepsis (RR 1.0, 95% CI 0.88 to 1.13) and all-cause mortality (RR 0.88, 95% CI 0.75 to 1.05). Catheter impregnation conferred significant benefit in studies conducted in intensive care units (RR 0.68, 95% CI 0.59 to 0.78) but not in studies conducted in haematological and oncological units or studies that assessed predominantly patients who required CVCs for long-term total parenteral nutrition. There were no differences between the impregnated and non-impregnated groups in the rates of adverse effects.

Full Text:  Lai. Catheter impregnation, coating or bonding for reducing central venous catheter-related infections in adults. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD007878


Cochrane Review:     Burns

Barajas-Nava performed a systematic review and meta analysis, identifying 36 randomized controlled trials (n=2117), to examine the effects of antibiotic prophylaxis on rates of burn wound infection. In 11 trials (n=645) topical prophylaxis with silver sulfadiazine, compared with dressings/skin substitute, was associated with both an increase in burn wound infection  (OR = 1.87; 95% CI: 1.09 to 3.19, I2 = 0%) and longer hospital stay (mean difference 2.11 days; 95% CI 1.93 to 2.28). Systemic antibiotic prophylaxis had no effect on burn wound infection in non-surgical patients (3 trials, n=119). Perioperative antibiotics also appeared ineffective. While selective digestive decontamination with non-absorbable antibiotics had no effect on rates of all types of infection (2 trials, n=140), there was an increase in rates of MRSA associated with use of non-absorbable antibiotics plus cefotaxime compared with placebo (RR = 2.22; 95% CI: 1.21 to 4.07). The evidence reviewed was limited, consisting of small studies at unclear or high risk of bias for each comparison.

Full Text:  Barajas-Nava. Antibiotic prophylaxis for preventing burn wound infection. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD008738


Cochrane Review:     Cardiac Surgery

Svircevic et al completed a systematic review and meta analysis (31 studies, n=3047) to evaluate the effect of perioperative epidural analgesia in cardiac surgery on perioperative mortality and cardiac, pulmonary or neurological morbidity. Compared with GA alone, GA with thoracic epidural analgesia had no effect on mortality (odds ratio 0.84, 95% CI 0.33 to 2.13, 31 studies), myocardial infarction (OR 0.76, 95% CI 0.49 to 1.19, 17 studies) or stroke (0.50, 95% CI 0.21 to 1.18, 10 studies). The risk of respiratory complications and supraventricular arrhythmias were both reduced with thoracic epidural analgesia (risk ratio 0.68, 95% CI 0.54 to 0.86, 14 studies and risk ratio 0.65, 95% CI 0.50 to 0.86, 15 studies, respectively).

Full Text:  Svircevic. Epidural analgesia for cardiac surgery. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD006715


Cochrane Review:     Alcohol Withdrawal

Sarai and colleagues completed a systematic review and meta analysis evaluating the effects of magnesium for the prevention or treatment of alcohol withdrawal syndrome in hospitalised adults. In 4 trials (n=317), all at high risk of bias, there was insufficient evidence to determine whether magnesium is beneficial or harmful for the treatment or prevention of alcohol withdrawal syndrome. 

Full Text:  Sarai. Magnesium for alcohol withdrawal. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD008358


Cochrane Review:     Inhalers versus Nebulizers

Holland et al undertook a a systematic review and meta analysis comparing the effectiveness of nebulizers and meter dose inhalers (MDI) for bronchodilator delivery in critically ill adults receiving invasive mechanical ventilation. Just 5 trials (n=64) were identified, leaving the authors unable to adequately address this evaluation.

Full Text:  Holland. Metered dose inhalers versus nebulizers for aerosol bronchodilator delivery for adult patients receiving mechanical ventilation in critical care units. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD008863


Cochrane Review:     Bacterial Meningitis

In an updated Cochrane Review, Brouwer and colleagues identified 25 studies (n=4121) investigating the efficacy of corticosteroids for bacterial meningitis in both children and adults. Corticosteroids were associated with a trend for reduced mortality in both analyses involving all patients (17.8% versus 19.9%; risk ratio 0.90, 95% CI 0.80 to 1.01, P = 0.07) and just adults (RR 0.74, 95% CI 0.53 to 1.05, P = 0.09). Corticosteroids were also associated with lower rates of severe hearing loss (RR 0.67, 95% CI 0.51 to 0.88), any hearing loss (RR 0.74, 95% CI 0.63 to 0.87) and neurological sequelae (RR 0.83, 95% CI 0.69 to 1.00). Subgroup analyses for causative organisms showed that corticosteroids reduced mortality in Streptococcus pneumoniae (S. pneumoniae) meningitis (RR 0.84, 95% CI 0.72 to 0.98), but not in Haemophilus influenzae (H. influenzae) or Neisseria meningitidis (N. meningitidis) meningitis. Corticosteroids reduced severe hearing loss in children with H. influenzae meningitis (RR 0.34, 95% CI 0.20 to 0.59) but not in children with meningitis due to non-Haemophilus species. In high-income countries, corticosteroids reduced severe hearing loss (RR 0.51, 95% CI 0.35 to 0.73), any hearing loss (RR 0.58, 95% CI 0.45 to 0.73) and short-term neurological sequelae (RR 0.64, 95% CI 0.48 to 0.85). There was no beneficial effect of corticosteroid therapy in low-income countries. Subgroup analysis for study quality showed no effect of corticosteroids on severe hearing loss in high-quality studies. Corticosteroid treatment was associated with an increase in recurrent fever (RR 1.27, 95% CI 1.09 to 1.47), but not with other adverse events.

Full Text:  Brouwer. Corticosteroids for acute bacterial meningitis. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD004405


Cochrane Review:     Myocardial Infarction

Moazzami completed a systematic review and meta analysis (7 studies, n=354) to assess the effects of stem cell mobilization following granulocyte colony stimulating factor therapy (subcutaneous administration of G-CSF through a daily dose of 2.5, 5 or 10 microgram/kg for four to six days or placebo) in patients with acute myocardial infarction. G-CSF had no effect on mortality (risk ratio 0.64, 95% CI 0.15 to 2.80, P = 0.55) or any beneficial effects on left ventricular function parameters, including left ventricular ejection fraction (RR 3.41, 95% CI -0.61 to 7.44, P = 0.1), end systolic volume (RR -1.35, 95% CI -4.68 to 1.99, P = 0.43) and end diastolic volume (RR -4.08, 95% CI -8.28 to 0.12, P = 0.06). There was insufficient evidence to assess the safety of G-CSF therapy. The review was limited by the short follow up of subjects.

Full Text:  Moazzami. Granulocyte colony stimulating factor therapy for acute myocardial infarction. Cochrane Database of Systematic Reviews 2013, Issue 5. Art. No.: CD008844


Cochrane Review:     Clostridium Difficile

Goldenberg assess the efficacy and safety of probiotics for preventing Clostridium difficile-associated diarrhea (CDAD) or C. difficile infection in adults and children. In 23 moderate-quality studies (n=4213) probiotics were associated with a reduced risk of CDAD (probiotics: 2.0% versus placebo: 5.5%; RR 0.36; 95% CI 0.26 to 0.51).

Full Text:  Goldenberg. Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children. Cochrane Database of Systematic Reviews 2013, Issue 5. Art. No.: CD006095


Cochrane Review:     Cardiogenic Pulmonary Oedema

In an updated Cochrane Review (32 studies, n=2916), Vital et al found that non-invasive positive pressure ventilation, compared with standard care, reduced hospital mortality (RR 0.66, 95% CI 0.48 to 0.89) and endotracheal intubation (RR 0.52, 95% CI 0.36 to 0.75 ) in adults with acute cardiogenic pulmonary oedema. There was no difference in hospital length of stay with NPPV; although intensive care unit stay was reduced by 1 day (weighted mean difference -0.89 days, 95% CI -1.33 to -0.45). NPPV was associated with no increase in the incidence of acute myocardial infarction during its application (RR 1.24, 95% CI 0.79 to 1.95) or after (RR 0.70, 95% CI 0.11 to 4.26), and also with fewer adverse events (progressive respiratory distress and coma) 

Full Text:  Vital. Non-invasive positive pressure ventilation (CPAP or bilevel NPPV) for cardiogenic pulmonary oedema. Cochrane Database of Systematic Reviews 2013, Issue 5. Art. No.: CD005351


Cochrane Review:     Ischaemic Stroke

Wardlaw et al undertook a systematic review and meta analysis to examine the risks and benefits of different thrombolytic agents, doses and routes of administration for the treatment of acute ischaemic stroke. A total of 20 studies (n=2527) were evaluated, with smaller numbers contributing to each specific analysis. Higher doses, in comparison with lower doses of the same thrombolytic, were associated with an approximately three-fold increase in fatal intracranial haemorrhages (odds ratio 2.71, 95% CI 1.22 to 6.04), although there was no difference in the number of patients dead or dependent at the end of follow-up (OR 0.86, 95% CI 0.62 to 1.19). Higher versus lower doses of desmoteplase were associated with more deaths at the end of follow-up (OR 3.21, 95% CI 1.23 to 8.39). There was no evidence of any benefit for intra-arterial over intravenous treatment. The evidence was inadequate to determine whether one agent is better than another, or which route of administration is the best, for acute ischaemic stroke. The authors concluded by recommending intravenous rt-PA at 0.9mg/kg as probably representing best practice and other drugs, doses or routes of administration should only be used in randomised controlled trials.

Full Text:  Wardlaw. Thrombolysis (different doses, routes of administration and agents) for acute ischaemic stroke. Cochrane Database of Systematic Reviews 2013, Issue 5. Art. No.: CD000514


Cochrane Review:     Subarachnoid Haemorrhage

Marigold and colleagues assessed the effects of anti-epileptic drugs (AED) for the primary and secondary prevention of seizures after subarachnoid haemorrhage. There were no relevant studies to inform current practice.

Full Text:  Marigold. Antiepileptic drugs for the primary and secondary prevention of seizures after subarachnoid haemorrhage. Cochrane Database of Systematic Reviews 2013, Issue 6. Art. No.: CD008710



Intensive Care Medicine:     Abdominal Compartment Syndrome



Journal of the American Medical Association:     Fructose

Review - Clinical


BMC Medicine:     Cerebral Circulation



European Heart Journal: Acute Cardiovascular Care:     Right Ventricular Infarction


Ulster Medical Journal:     Endovascular Aortic Aneurysm Repair


Swiss Medical Weekly:     Paediatric LVADs


BMC Medicine:     Cardiac Circulation


Cleveland Clinic Journal of Medicine:     Premature Ventricular Complexes


Journal of the American College of Cardiology:     Thoracic Irradiation Cardiac Complications



Expert Reviews in Respiratory Medicine:     Lung Protective Ventilation


Anesthesia News:     Difficult Airway


Cerebrovascular Disease:     Stroke


Ulster Medical Journal:     Chest Radiograph



Cleveland Clinic Journal of Medicine:     Acute Pancreatitis


Gastroenterology Research and Practice:     Small Intestine Imaging



Gastroenterology Research and Practice:     Acute Liver Failure


Ulster Medical Journal:     Liver Function Tests


World Journal of Hepatology:     Cirrhosis



Blood Purification:     Artificial Kidney


International Journal of Nutrition, Pharmacology and Neurological Diseases:     Thyroid Disorders



Swiss Medical Weekly:     Peptidomics & Metabolomics



Annals of Intensive Care:     Plasma in Paediatrics



Journal of Pharmacy and Pharmaceutical Sciences:     Carnitine in Sepsis


ISRN Critical Care


Ulster Medical Journal:     Upper Limb Injury



The Scientific World Journal:     Cadmium Toxicity



Ulster Medical Journal:     Radiological Error



Recently Made Open Access Articles from Major Journals


American Journal of Respiratory and Critical Care Medicine



Critical Care


Anesthesia & Analgesia




Continuing Education in Anaesthesia, Critical Care and Pain



British Journal of Anaesthesia


American Journal of Respiratory and Critical Care Medicine




Critical Care



Anaesthesia:     Anaesthetic Equipment


Study Critique

Critical Care


Review - Basic Science

Canadian Journal of Surgery:     Statistics


Indian Journal of Dermatology, Venereology, and Leprology:     Genetics


Review - Non-Clinical

Ulster Medical Journal:     Metric-Based Simulation


I hope you find these brief summaries and links useful.

Until next week