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Critical Care Reviews Newsletter

August 4th 2013



Welcome to the 87th 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 randomised trials on low tidal volume ventilation, this time in the perioperative setting, anti-oxidants for atrial fibrillation and N-acetylcysteine for contrast-induced nephropathy; the fallout from the DECREASE debacle continues, with a meta analysis reporting increased mortality with the perioperative initiation of beta blockers, while observational studies describe pipercillin/tazobactam kinetics during continuous renal replacement therapy and suggest benefit from panscanning in major trauma. The major study this week is likely to be very influential and describes a 40% incidence of medical reversal (i.e. current medical practice is wrong) based on a 10 year analysis of papers published in the New England Journal of Medical.

This week's guidelines are on blood gas analysis and acquired coagulation inhibitors, while there are 9 editorials, addressing fluids, ARDS, blood transfusion, organ donation, heart failure, H7N9 influenza and organ donation. There are two study critiques, once again on BEST TRIP, and on SLEAP.

There are two commentaries on acute medical care and medical writing. Amongst the 25 clinical review articles are papers on subarachnoid haemorrhage, cardiogenic shock, inhaled nitric oxide, the role of ultrasound in the management of the acute abdomen, alcoholic hepatitis, hazards of blood transfusion, and procalcitonin. Non-clinical review articles address statistics, animal research and open access journals. If it's all a bit too serious, there always Lemmingaid, from the Journal of the Intensive Care Society.

Given the theme of flawed research and medical reversal in today's newsletter, the topic for This Week's Papers is scientific rigor in critical care research, starting with a paper on delta inflation in tomorrow's Paper of the Day.



Randomized Controlled Trial

New England Journal of Medicine:     Low Tidal Volume Ventilation

In a multicenter, randomized, double-blind, parallel-group trial, Futier and colleagues compared lung-protective ventilation (n=200, tidal volume of 6 to 8 mL/kg predicted body weight, positive end-expiratory pressure of 6 to 8 cm water, and recruitment maneuvers repeated every 30 minutes after tracheal intubation) with nonprotective ventilation (n=200, tidal volume of 10 to 12 mL/kg, and neither positive end-expiratory pressure nor recruitment maneuvers) in 400 adults at intermediate to high risk of pulmonary complications after major abdominal surgery. Lung protective ventilation was associated with a reduced incidence of the primary outcome, a composite of major pulmonary and extrapulmonary complications occurring within the first 7 days after surgery (10.5% versus 27.5%; relative risk 0.40; 95% CI 0.24 to 0.68; P=0.001). Protective ventilation was also associated with both a reduced requirement for non-invasive ventilation (5% versus 17%; relative risk 0.29; 95% CI 0.14 to 0.61; P=0.001) and shorter length of hospital stay (mean difference −2.45 days; 95% CI −4.17 to −0.72; P=0.006).

Abstract:  Futier. A Trial of Intraoperative Low-Tidal-Volume Ventilation in Abdominal Surgery (IMPROVE study). N Engl J Med 2013; 369:428-437

Journal of the American College of Cardiology:     Atrial Fibrillation

In 203 patients scheduled to on-pump cardiac surgery, Rodrigo and colleagues demonstrated, in comparison with placebo (n=100), a reduced rate of post-operative atrial fibrillation (9.7% versus 32%, p<0.001) with supplementation (n=103) of n-3 polyunsaturated fatty acids (2 g/d) (EPA:DHA ratio 1:2), vitamin C (1 g/d), and vitamin E (400 IU/d). Biomarkers of inflammation and oxidative stress were also reduced with anti-oxidants, with atrial tissue levels of the anti-oxidants catalase, superoxide dismutase and glutathione peroxidase increased by 24.0%, 17.1%, and 19.7% respectively (p<0.05).

Abstract:  Rodrigo. A Randomized Controlled Trial to Prevent Postoperative Atrial Fibrillation by Anti-oxidant Reinforcement. J Am Coll Cardiol 2013;epublished July 31st


Annals of Emergency Medicine:     Contrast-Induced Nephropathy

In a randomized, double blind, two center, placebo-controlled trial, comparing N-acetylcysteine (n=185, 3 g in 500 mL normal saline as an intravenous bolus and then 200 mg/hour (67 mL/hour) for up to 24 hours) with normal saline alone (n=172, 500 mL normal saline and then 67 mL/hour for up to 24 hours.) for the prevention of contrast-induced nephropathy in 357 at risk emergency department patients, defined as an increase in creatinine level of 25% or 0.5 mg/dL / 44.2 μmol/L, measured 48 to 72 hours after CT. The study was stopped early for futility, with no difference in rates of contrast-induced nephropathy (NAC: 7.6% versus saline 7.0%; absolute risk difference 0.6%; 95% CI − 4.8% to 6.0%. The volume of saline administered appeared protective, with those receiving greater than 1L, in comparison with less than 1L, having a 69% risk reduction in rates of acute kidney injury (3.3% versus 12.9%; odds ratio 0.41; 95% CI 0.21 to 0.80) per liter of intravenous fluids.

Abstract:  Traub. N-Acetylcysteine Plus Intravenous Fluids Versus Intravenous Fluids Alone to Prevent Contrast-Induced Nephropathy in Emergency Computed Tomography. Annals of Emergency Medicine 2013;epublished June 17th


 Meta Analysis

Heart:     Perioperative Beta Blockade

Following the controversy regarding the veracity of the Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography (DECREASE) family of perioperative β-blockers trials, Bouri and colleagues performed meta analyses on randomised controlled trials of the initiation of β-blockers before non-cardiac surgery, examining the DECREASE trials and non-DECREASE trials seperately. In nine non-DECREASE trials (n=10 529, 291 deaths) the initiation of a course of β-blockers before surgery caused a 27% risk increase in 30-day all-cause mortality (p=0.04), and are significantly different to the results of the DECREASE studies meta analysis (p=0.05 for divergence). In the non-DECREASE studies, which were dominated by one large study, β-blockade reduced non-fatal myocardial infarction (RR 0.73, p=0.001) but increased stroke (RR 1.73, p=0.05) and hypotension (RR 1.51, p<0.00001).

Full Text:  Bouri. Meta-analysis of secure randomised controlled trials of β-blockade to prevent perioperative death in non-cardiac surgery. Heart 2013;epublished July 31st


Observational Study

Mayo Clinic Proceedings:     Evidence Reversal

In an attempt to identify medical practices that offer no net benefits, Prasad and colleagues reviewed all original articles published from 2001-2010 in the New England Journal of Medicine, the highest impact medical journal. 2044 original articles were reviewed, with 1344 concerning a medical practice, of which 981 articles (73.0%) examined a new medical practice, whereas 363 (27.0%) tested an established practice. 947 studies (70.5%) had positive findings, and 397 (29.5%) negative findings. In 756 articles, the new medical practice surpassesed current standard of care, in 165 articles, the new practice was no better than current practice, in 146 articles, current practice was not superior to supposedly inferior therapies, 138 articles provided reaffirmations, where an existing practice was found to be better than a lesser standard, while 139 were inconclusive. Of the 363 articles testing standard of care, 146 (40.2%) reversed that practice, whereas 138 (38.0%) reaffirmed it. These results occured across all classes of medical practice.

Full Text:  Prasad. A Decade of Reversal: An Analysis of 146 Contradicted Medical Practices. Mayo Clinic Proceedings 2013;epublished July 22nd


Journal of Antimicrobial Chemotherapy:     Pipercillin/Tazobactam CRRT Kinetics

To examine the pharmacokinetics and antimicrobial activity of piperacillin/tazobactam in critically ill patients undergoing continuous renal replacement therapy (CRRT), Asín-Prieto and colleagues evaluated 16 patients undergoing CRRT and found kinetics of piperacillin/tazobactam were best described by two-compartment models where the elimination of both drugs was conditioned by renal [dependent on creatinine clearance (CLCR)], non-renal and extracorporeal clearances. A 20 min infusion of piperacillin/tazobactam administered every 6 h provided high probability of target attainment against minimum inhibitory concentrations ≤32 mg/L in patients with severe renal failure, while patients with normal or moderate renal function probability of target attainments ≥90% were only obtained up to minimum inhibitory concentrationss ≤8 mg/L with short infusions. Simulating continuous infusions, higher probabilities of success were obtained against minimum inhibitory concentrations of 32 and 16 mg/L when CLCR was 50 and 100 mL/min, respectively.

Abstract:  Asín-Prieto. Population pharmacokinetics of piperacillin and tazobactam in critically ill patients undergoing continuous renal replacement therapy: application to pharmacokinetic/pharmacodynamic analysis. J Antimicrob Chemother 2013;epublished August 1st


PLoS ONE:     PanScan

Huber-Wagner and completed a retrospective multicenter cohort study in 16,719 adult blunt major trauma patients and compared the survival of patients who were in moderate, severe or no shock (systolic blood pressure 90–110,<90 or >110 mmHg) at hospital admission and who received whole body CT (WBCT) (n=9,233; 55.2%) during resuscitation to those who did not. Less people who underwent WBCT died (17.4% versus 21.4%) than those without WBCT (p<0.001). This difference was maintained in the subgroups of patients with moderate (18.1% versus 22.6%, p<0.001) and severe shock (42.1% versus 54.9%; p<0.001). Using logistic regression, WBCT was an independent predictor for survival in both moderate shock (OR = 0.73; 95% CI 0.60–0.90, p = 0.002) and severe shock (OR = 0.67; 95% CI 0.52–0.88, p = 0.004). The number needed to scan related to survival was 35 for all patients, 26 for those in moderate shock and 20 for those in severe shock.

Full Text:  Huber-Wagner.  Whole-Body CT in Haemodynamically Unstable Severely Injured Patients – A Retrospective, Multicentre Study. PLoS ONE 2013;8(7):e68880


Statistics in Medicine:     Observational Study Results

In a statistical study, Schumie and colleagues took three high quality observational studies (a case–control, a cohort, and a self-controlled case series), and attempted to replicate the analysis, as well as replicating these studies with sets of negative controls. It was observed how often p  < 0.05 when the null hypothesis was true, with distributions being fitted to the effect estimates. Using an automated analysis of the scientific literature to evaluate the potential impact of such a calibration, it was found at least 54% of findings with p < 0.05 are not actually statistically significant.

Full Text:  Schuemie.  Interpreting observational studies: why empirical calibration is needed to correct p-values. Statist Med 2013;epublished July 30th


Study Critique

Journal of the Intensive Care Society:     BEST TRIP study

Journal of the Intensive Care Society:     SLEAP study



European Journal of Anaesthesiology:     Fluids


Critical Care:     ARDS


Journal of Critical Care:     World Sepsis Day


Journal of Critical Care:     H7N9 Influenza


Journal of the Intensive Care Society:     ARDS


Journal of the Intensive Care Society:     Blood Transfusion


Journal of the Intensive Care Society:     Organ Donation


HSR Proceedings in Intensive Care and Cardiovascular Anesthesia:     Heart Failure



New England Journal of Medicine:     Acute Care


HSR Proceedings in Intensive Care and Cardiovascular Anesthesia:     Medical Writing


Review - Clinical


Journal of Medicine and Life:    Subarachnoid Haemorrhage 


Rambam Maimonides Medical Journal:     Brain Injury


Korean Journal of Anesthesiology:  Suggamadex



Journal of the Intensive Care Society:     Cardiogenic Shock


Journal of the Intensive Care Society:     Mechanical Heart Support


Translational Medicine @ UniSa:     Refractory Shock


Current Opinion in Cardiology:     β Blockade post MI

Circulation Research:     Heart Failure

Critical Care Nurse:     Hypertriglyceridemia


HSR Proceedings in Intensive Care and Cardiovascular Anesthesia:     Congenital Heart Disease


HSR Proceedings in Intensive Care and Cardiovascular Anesthesia:     Coronary Revascularization


Vascular Health and Risk Management:    Coronary Artery Disease Biomarkers



Journal of the Intensive Care Society:     Inhaled Nitric Oxide


Transplantation Reviews:     Protective Ventilation



Critical Ultrasound Journal:     Acute Abdomen


Critical Ultrasound Journal:     Abdominal Vascular Emergencies


Journal of Medicine and Life:    Upper Gastrointestinal Bleeding



Journal of Medicine and Life:    Alcoholic Hepatitis



Kidney International:     ANCA-Associated Vasculitis



Journal of the Intensive Care Society:     Hazards of Transfusion


Blood Transfusion:     Blood-Borne Pathogens

Thrombosis Journal:     New Oral Anticoagulants



Journal of the Intensive Care Society:     Procalcitonin


North American Journal of American Science:     H7N9 Influenza



New England Journal of Medicine:     Global Disease Burden


Review - Basic Science

Translational Medicine @ UniSa:     Statistics


PLoS Medicine:     Animal Research


Review - Non-Clinical

Annals of Emergency Medicine:     Open Access Journals


If it's all too much....

Journal of the Intensive Care Society:     Lemmingaid



I hope you find these brief summaries and links useful.

Until next week


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