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Critical Care Reviews Newsletter

July 28th 2013



Welcome to the 86th 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 busy period behind the scenes and I've finally (with help) upgraded to a redesigned website. It's still a work in progress, as some of the links need to be reset, and unfortunately some functionality (submenus) has been lost for the gain of others (more modern look and easier to manage the site). Take a look and let me know what you think.

This week's research studies include randomized controlled trials investigating hepatic encephalopathy, stroke and delirium; meta analyses evaluating ventilator-associated pneumonia, BNP, intra-operative oxygenation, hydroxyethyl starches and antioxidants; as well as observational studies examining hyperchloraemic fluids, low tidal volume ventilation, acute kidney injury, outcomes of ventilated oncology patients, and massive transfusion. The newest Cochrane reviews address venothromboembolism prophylaxis, soft tissue infections, perioperative statins, tracheal intubation, and cervical spinal cord injuries. Updated Cochrane reviews cover partial liquid ventilation, venothromboembolism prophylaxis for prosthetic heart valves, hydroxyethyl starches and, again, low molecular weight heparins for venothromboembolism prophylaxis.

This week's position statements concern stroke and ECMO, and there are editorials on focued echo, ECMO and futuristic developments in monitoring. There are commentaries on antibiotic resistance, tranexamic acid and randomized controlled trials. Interesting news that caught me attention includes an appeal against the Europena ban on hydroxyethyl starches and the discovery of a whole new form of viruses, which share less than 10% of their DNA with the rest of the biosphere.

Amongst the clinical review articles are papers on subarachnoid haemorrhage, outcome post cardiac arrest, inotropes during cardiac ischaemia, ECMO, ventilator-associated pneumonia, non-invasive ventilation, gut dysfunction, perioperative liver injury plus postoperative kidney injury, hydroxyethyl starches, new oral anticoagulants, toxic alcohols and maternal cardiac arrest.

The topic for This Week's Papers is tracheostomy, starting with a general management paper in tomorrow's Paper of the Day.



  • The European Medicines Agency's Pharmacovigilance Risk Assessment Committee have commenced a review of it's decision to supend marketing approval for hydroxyethyl starches, following an appeal by a number of marketing authorisation holders.


Science:     Fourth Domain of Life



Randomized Controlled Trials

Journal of Hepatology:     Hepatic Encephalopathy

Simón-Talero and colleagues randomized 56 cirrhotic patients with an acute episode of hepatic encephalopathy (grade II-IV) to receive either albumin (1.5 g/Kg on day 1 and 1.0 g/Kg on day 3) (n=26) or saline (n=30), in addition to the usual treatment of laxatives and rifaximin 1200 mg per day. Baseline characteristics were similar between groups. There was no difference in the primary endpoint of the percentage of patients without hepatic encephalopathy at day 4 (albumin: 57.7% vs. saline: 53.3%; p > 0.05), although there was a survival effect at day 90 (albumin: 69.2% vs. saline: 40.0%; P = 0.02).

Abstract:  Simón-Talero. Effects of intravenous albumin in patients with cirrhosis and episodic hepatic encephalopathy: A randomized double-blind study. J Hepatol 2013;epublished July 18th


Stroke:     Chinese Medicine Neuroaid

Chen et al undertook a multicenter, randomized, double-blind, placebo-controlled trial evaluating MLC601 in 1100 patients with a National Institutes of Health Stroke Scale score of 6 to 14, within 72 hours of onset. There was no difference in the primary outcome of improved modified Rankin Scale (adjusted odds ratio 1.09; 95% CI 0.86–1.32) or various secondary outcomes of stroke severity. In a prespecified subgroup analysis, a trend for improvement was noted in those receiving MLC601 48 hours after the onset of stroke. There was no difference in adverse effects.

Abstract:  Chen. Chinese Medicine Neuroaid Efficacy on Stroke Recovery: A Double-Blind, Placebo-Controlled, Randomized Study (CHIMES). Stroke 2013;44:2093-2100


Drug Design, Development and Therapy:     Delirium

Maneeton and colleagues completed a 7-day prospective, double-blind, randomized controlled trial in 52 delirious Asian medically ill patients able to tolerate oral medications, comparing quetiapine (25–100 mg/day; n = 24) or haloperidol (0.5–2.0 mg/day; n = 28).  Doses of quetiapine and haloperidol were low, at (mean(SD)) 67.6 (9.7) and 0.8 (0.3) mg/day, respectively. The primary outcome, the DRS-R-98 severity score, was similar between the groups  (quetiapine -22.9 (6.9) versus haloperidol -21.7 (6.7); P = 0.59). There was no difference in the other trial measures of DRS-R-98 noncognitive and cognitive subscale scores, response and remission rates, total sleep time, modified (nine-item) Simpson–Angus scores or hypersomnia. 

Full Text:  Maneeton. Quetiapine versus haloperidol in the treatment of delirium: a double-blind, randomized, controlled trial. Drug Design, Development and Therapy 2013;2013(7):657-667


Meta Analysis

Lancet Infectious Diseases:     Ventilator-Associated Pneumonia

In a systematic review and meta analysis, including 6284 patients from 24 trials, Melsen and colleagues estimated the overall attributable mortality from ventilator-associated pneumonia to be 13%. There were higher mortality rates in surgical patients and patients with mid-range severity scores at admission (APACHE 20—29 and SAPS 2  35—58) and an attributable mortality close to zero in trauma, medical patients, and patients with low or high severity of illness scores. In a competing risk analyses in 5162 patients from 19 studies, the overall daily ICU mortality hazard after ventilator-associated pneumonia was 1·13 (95% CI 0·98—1·31), with an overall daily risk of discharge after ventilator-associated pneumonia of 0·74 (0·68—0·80), leading to an overall cumulative risk for dying in the ICU of 2·20 (1·91—2·54).

Abstract:  Melsen. Attributable mortality of ventilator-associated pneumonia: a meta-analysis of individual patient data from randomised prevention studies. Lancet Infectious Diseases 2013;13(8):665-671


Anesthesiology:     B-type Natriuretic Peptide

Using a systematic review and individual patient data meta-analysis, including 18 studies and 2,051 patients, Rodseth et al determined a modest predictive ability of BNP > 245 pg/ml (AUC 0.71; 95% CI 0.64–0.78), and a good predictive ability of N-terminal proBNP > 718 pg/ml (AUC 0.80; 95% CI 0.77–0.84) for non cardiac surgery postoperative 30-day mortality or nonfatal myocardial infarction. The adjusted odds ratio for 30 day predictions for these values were: mortality or nonfatal myocardial infarction 4.5; 95% CI 2.74–7.4; P < 0.001; mortality 4.2; 95% CI 2.29–7.69; P < 0.001; cardiac mortality 9.4, 95% CI 0.32–254.34, P < 0.001; and cardiac failure 18.5, 95% CI 4.55–75.29, P < 0.001. Similarly, the 180 day adjusted odds ratio for mortality or nonfatal myocardial infarction was 3.3; 95% CI 2.58–4.3, P < 0.001; mortality 2.2, 95% CI 1.67–86, P < 0.001; cardiac mortality 2.1, 95% CI 0.05–1,385.17, P < 0.001; and cardiac failure 3.5; 95% CI 1.0–9.34; P = 0.022). Increasing levels of both BNP and N-terminal proBNP were associated with increasing rates of death or nonfatal myocardial infarction.

Full Text:  Rodseth. Postoperative B-type Natriuretic Peptide for Prediction of Major Cardiac Events in Patients Undergoing Noncardiac Surgery: Systematic Review and Individual Patient Meta-analysis. Anesthesiology 2013;119(2):270-283


Anesthesiology:     Intra-Operative Oxygenation

Pooling 9 trials (n=5,103) comparing intraoperative high (80% - 100%) with normal (30 - 40%) inspired oxygen concentration in adults undergoing surgery with general anesthesia, high Fio2 was associated with a decreased incidence of surgical site infections (11.4% versus 14.1%, risk ratio 0.77, 95% CI 0.59–1.00) in patients already receiving antimicrobial prophylaxis. Similarly, in colorectal surgery high Fio2 was associated with decreased incidence of surgical site infection (15.2% versus 19.3%, risk ratio 0.78, 95% CI, 0.60–1.02). High Fio2 did not increase the risk of atelectasis (9 trials, n=3,6980), and was associated with a decreased incidence of nausea (19.5% versus 24.8%, risk ratio 0.79, 95% CI, 0.66–0.93).

Full Text:  Hovaguimian. Effect of Intraoperative High Inspired Oxygen Fraction on Surgical Site Infection, Postoperative Nausea and Vomiting, and Pulmonary Function: Systematic Review and Meta-analysis of Randomized Controlled Trials. Anesthesiology 2013;119(2):303-316


Critical Care:     Hydroxyethyl Starches

In a re-evaluation of data from prospective randomised controlled trials from four meta-analyses published in 2013, comparing the effect of hydroxyethyl starches with crystalloids in critically ill patients, Meybohm and colleagues addressed whether the studies evaluated were adherent to 'presumably correct indication', defined as the presence of six criteria (max. six points): short time interval from shock to randomisation (< 6 h), restricted use for initial volume resuscitation, use of any consistent algorithm for haemodynamic stabilisation, reproducible indicators of hypovolaemia, maximum dose of HES, and exclusion of patients with pre-existing renal failure or renal replacement therapy. These studies showed a large heterogeneity of the indication score (median 4 points, IQR 1 to 4) with the authors concluding harm from HES, when it is limited to immediate haemodynamic stabilisation, cannot be determined based on the studies examined.

Full Text:  Meybohm. Re-evaluating currently available data and suggestions for planning randomised controlled studies regarding the use of hydroxyethyl-starch in critically ill patients - a multidisciplinary statement. Critical Care 2013;17:R166



Anesthesia & Analgesia:     Fluids

In a retrospective observational study evaluating 22,851 surgical patients with normal preoperative serum chloride concentration and renal function, acute postoperative hyperchloremia (serum chloride >110 mmol/L) occurred with an incidence of 22%. Using propensity matching, comparing 80% (n=4,266) of the total 4,955 hyperchloraemic cohort with normochloraemic post-operative patients, hyperchloraemia was associated with an increased 30 day mortality risk (3.0% vs 1.9%; odds ratio 1.58; 95% CI 1.25–1.98) (relative risk 1.6 ), increased risk of renal dysfunction and longer hospital stay (7.0 days [IQR 4.1–12.3] versus 6.3 [IQR 4.0–11.3]).

Abstract:  McCluskey. Hyperchloremia After Noncardiac Surgery Is Independently Associated with Increased Morbidity and Mortality: A Propensity-Matched Cohort Study. Anesth Analg 2013;117:412-421


Critical Care:     Low Tidal Volume Ventilation

In a crossover randomized clinical trial in 16 ARDS patients, each being ventilated for 30 minutes with low (6 ml/kg) and 30 minutes with high (12 ml/kg) tidal volume, low TV ventilation was associated with (1) decreased pH (7.37 vs. 7.41, P=0.001) and increased PaCO2 (49 vs. 43 mmHg; P=0.002), (2) increased cardiac index and oxygen delivery index (3.9 vs. 3.5 L/min/m2, P=0.012, and 521 vs. 463 mL/min/m2, P=0.002, respectively), and (3) decreased oxygen extraction ratio (0.36 vs. 0.44, P=0.027). The change in cardiac index was positively associated with PaCO2 variation (P=0.004).

Full Text:  Natalini. Cardiac index and oxygen delivery during low and high tidal volume ventilation strategies in patients with acute respiratory distress syndrome: a crossover randomized clinical trial. Crit Care 2013;17(4):R146


Critical Care:     Acute Kidney Injury

Using a population-based registry to identify all 107,937 adult patients who survived for 90 days after ICU admission in Denmark from 2005 through 2010, 3062 (2.8%) had an episode of acute kidney injury requiring dialysis following ICU admission. The subsequent risk of end stage renal disease (ESRD) up to 180 days after ICU admission was 8.5% for this cohort, compared with 0.1% for other ICU patients (adjusted hazard ratio 105.6, 95% CI 78.1-142.9). For patients who survived 180 days after ICU admission without developing ESRD (n = 103,996), the 181-day to five-year ESRD risk was 3.8% for patients requiring dialysis, compared with 0.3% for other ICU patients (adjusted hazard ratio 6.2, 95% CI 4.7-8.1). Younger patients (adjusted HR 12.8, 95% CI 6.5-25.4) and patients without preexisting chronic kidney disease (adjusted HR 11.9, 95% CI: 8.5-16.8) fared worst following an episode of ICU AKI.

Full Text:  Gammelager. Five-year risk of end-stage renal disease among intensive care patients surviving dialysis-requiring acute kidney injury: a nationwide cohort study. Critical Care 2013;17:R145


Canadian Journal of Anaesthesia:     Massive Transfusion

Examining 971,455 patients from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database, Turan and colleagues determined the crude 30-day postoperative mortality of non-transfused, low transfusion (1-4 units), and massive transfusion (≥ 5 units) patients to be 1.2%, 8.9%, and 21.5%, respectively. Of the 5,143 massive transfusion patients with full available data, 17% (95% CI 16% to 18%) died within 30 days of surgery, while 54% (95% CI 53% to 56%) had at least one non-fatal major complication.

Abstract: Turan. Morbidity and mortality after massive transfusion in patients undergoing non-cardiac surgery. Can J Anesth 2013;60(8):761-770


Cochrane Reviews

New Reviews


Updated Reviews


Position Statement




Canadian Journal of Anaesthesia:     Focused Ultrasound


South African Journal of Critical Care:     ECMO


Nature:     Monitoring




Perspectives in Clinical Research:     Randomized Controlled Trials


Review - Clinical


Vascular Health and Risk Management:     Subarachnoid Haemorrhage



Deutsches Ärzteblatt International:     Post Cardiac Arrest Prognosis

Anesthesiology:    Inotropes in Cardiac Ischaemia

International Journal of Molecular Science:     Edaravone

Journal of Cardiothoracic Surgery:     CABG Outcome Biomarkers

Clinical Medicine Insights: Cardiology:     Everolimus Stents



Deutsches Ärzteblatt International:     Extracorporeal Gas Exchange

Antibiotics:     Ventilator Associated Pneumonia

International Journal of Chronic Obstructive Pulmonary Disease:     COPD

Respiratory Care:     Non-Invasive Ventilation

Respiratory Care:     Respiratory Therapists


Indian Journal of Anaesthesia:     Perioperative Liver Injury



Deutsches Ärzteblatt International:     Hydroxylethyl Starch

Anesthesiology:    Acute Kidney Injury



Journal of the Scientific Society:     Insulin Administration



Anesthesiology:     New Oral Anticoagulants

Seminars in Thrombosis and Hemostasis:     New Oral Anticoagulants



Journal of the Formosan Medical Association:     Middle East Respiratory Syndrome


Emergency Medicine International:     Toxic Alcohol Ingestion



Emergency Medicine International:     Maternal Cardiac Arrest

Indian Journal of Pharmaceutical Sciences:     Leeches


Review - Basic Science

Indian Journal of Clinical Medicine:     Monoclonal Antibodies


Drug Design, Development and Therapy:     Drug Targeting


Review - Non-Clinical

Canadian Journal of Anaesthesia:     Trial Reporting


Perspectives in Clinical Research:     Coding Data



I hope you find these brief summaries and links useful.

Until next week



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