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Critical Care Reviews Newsletter

December 23^rd 2012

Welcome

Merry Christmas

Welcome to the 55th 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 a French propensity analysis failing to demonstrate any advantage with the use of renal replacement therapy in the critically ill, a randomized controlled trial demonstrating superior outcomes with a BNP guided ventilatory weaning protocol, and a suggestion that critically ill obese people survive better than their leaner counterparts. An interesting Cochrane Review reports more favourable outcomes in industry sponsored studies, while an updated review confirms the lack of efficacy of activated protein C in severe sepsis. A report from the American Heart Association details the epidemiology of coronary and cerebrovascular disease in the USA, describing 68% of adults being overweight or obese, 33% having hypertension and approximately 12% being diabetic. This equates to one in every 6 deaths resulting from coronary disease and one in every 19 deaths from stroke.

There are three American guidelines on the management of ST elevation myocardial infarction, stable ischaemic heart disease and device based therapy for dysrhythmias.

Amongst the numerous clinical review articles are papers on aortic stenosis, respiratory failure in cancer patients, non-alcoholic liver disease, the seemingly obligatory paper on renal biomarkers, and two papers on newer anticoagulants.

The topic for This Week's Papers is neurological therapies, starting with a paper on red cell transfusion in neurocritical care in tomorrow's Paper of the Day.

Research

Critical Care: Renal Replacement Therapy

In the absence of a renal replacement therapy (RRT) versus no RRT study in the critically ill, Clec'h and colleagues performed a propensity analysis using data from the French longitudinal prospective multicenter Outcomerea database to assess the efficacy of RRT in the critically ill. Two propensity scores for RRT were built to match patients who received RRT to controls who did not despite having a close probability of receiving the procedure. Among the 2846 study patients, 545 (19%) received RRT. Crude mortality rates were higher in patients with than in those without RRT (38% vs 17.5%, p < 0.001). After matching and adjustment, RRT was not associated with a reduced hospital mortality. The two propensity models yielded concordant results.

Full Text: Clec'h. Efficacy of renal replacement therapy in critically ill patients: a propensity analysis. Critical Care 2012;16:R236

Amercan Journal of Respiratory and Critical Care Medicine: Fluid Management

Dessap et al performed a randomized controlled multicenter study, in 304 critically ill patients mechanically ventilated with an automatic computer-driven weaning system, to investigate whether fluid management guided by daily BNP plasma levels improved weaning compared with empirical therapy dictated by clinical acumen. In the BNP-driven group, furosemide and acetazolamide were given more often and in higher doses than in the control group, resulting in a more negative median (interquartile range) fluid balance during weaning (–2,320 [–4,735, 738] vs. -180 [–2,556, 2,832] ml; P < 0.0001). Time to successful extubation was significantly shorter with the BNP-driven strategy (58.6 [23.3, 139.8] vs. 42.4 [20.8, 107.5] h; P = 0.034). The BNP-driven strategy increased the number of ventilator-free days but did not change length of stay or mortality. The effect on weaning time was strongest in patients with left ventricular systolic dysfunction. The two strategies did not differ significantly regarding electrolyte imbalance, renal failure, or shock.

Abstract: Dessap. Natriuretic Peptide–driven Fluid Management during Ventilator Weaning: A Randomized Controlled Trial. Am J Respir Crit Care Med 2012;186:1256-1263

Critical Care: Effect of Obesity

In a cohort analysis from a single-centre database of 16,812 critically ill American patients, Abhyankar et al showed that compared to normal weight patients, obese patients had 26% and 43% lower mortality risk at 30 days and one year after ICU admission, respectively (OR 0.74; 95% CI: 0.64-0.86 and 0.57; 95% CI: 0.49-0.67); overweight patients had nearly 20% and 30% lower mortality risk (OR 0.81: 95% CI, 0.70-0.93 and 0.68; 95% CI: 0.59-0.79). Severely obese patients (BMI ≥ 40 kg/m2) did not have a significant survival advantage at 30 days (OR 0.94; 95% CI; 0.74-1.20), but did have 30% lower mortality risk at one year (OR 0.70; 95% CI: 0.54-0.90). There was no significant difference in admission acuity or ICU and hospital length of stay across BMI categories.

Full Text: Abhyankar. Lower short- and long-term mortality associated with overweight and obesity in a large cohort study of adult intensive care unit patients. Critical Care 2012;16:R235

Cochrane Review: Activated Protein C

In an update review, including the results of PROWESS-Shock, Martí-Carvajal and colleagues assessed the efficacy of activated protein C in severe sepsis. Six randomized clinical trials involving 6781 subjects were identified, with all studies sponsorsed by the pharmaceutical industry and all having a high risk of bias. APC compared with placebo did not significantly affect all-cause mortality at day 28 compared with placebo (780/3435 (22.7%) versus 767/3346 (22.9%); RR 1.00, 95% CI 0.86 to 1.16; I(2) = 56%). APC did not significantly affect in-hospital mortality (393/1767 (22.2%) versus 379/1710 (22.1%); RR 1.01, 95% CI 0.87 to 1.16; I(2) = 20%). APC was associated with an increased risk of serious bleeding (113/3424 (3.3%) versus 74/3343 (2.2%); RR 1.45, 95% CI 1.08 to 1.94; I(2) = 0%). APC did not significantly affect serious adverse events (463/3334 (13.9%) versus 439/3302 (13.2%); RR 1.04, 95% CI 0.92 to 1.18; I(2) = 0%). Trial sequential analyses showed that more trials do not seem to be needed for reliable conclusions regarding these outcomes.

Full Text: Martí-Carvajal. Human recombinant protein C for severe sepsis and septic shock in adult and paediatric patients. Cochrane Database Syst Rev. 2012 Dec 12;12:CD004388

Cochrane Review: Industry Involvement in Research

Lundh and colleagues performed a systematic review and meta-analysis, including 48 studies, to investigate whether industry sponsored drug and device studies have more favorable outcomes and differ in risk of bias, compared with studies having other sources of sponsorship. Industry sponsored studies more often had favorable efficacy results, risk ratio (RR): 1.24 (95% CI: 1.14 to 1.35), harms results RR: 1.87 (95% CI: 1.54 to 2.27) and conclusions RR: 1.31 (95% CI: 1.20 to 1.44) compared with non-industry sponsored studies. In industry sponsored studies, there was less agreement between the results and the conclusions than in non-industry sponsored studies, RR: 0.84 (95% CI: 0.70 to 1.01).

Full Text: Lundh. Industry sponsorship and research outcome. Cochrane Database of Systematic Reviews 2012, Issue 12. Art. No.: MR000033.

Comment: Hynes. Cochrane review questions value of industry-funded clinical trials. CMAJ 2012;10.1503/cmaj.109-4378

Circulation: Coronary and Cerebrovascular Disease Statistics

Full Text: Go. Heart Disease and Stroke Statistics--2013 Update - A Report From the American Heart Association. Circulation 2012; epublished December 12th

Study Announcement: Factor Xa Inhibitor Antidote

Following completion of a phase 1 single ascending dose safety and tolerability study of PRT4445, a novel recombinant protein and a potential universal antidote for Factor Xa inhibitor anticoagulants, Portola Pharmaceuticals has announced a Phase 2 study evaluating the safety and effectiveness of this agent in healthy volunteers who have been administered approved and investigational Factor Xa inhibitors, including the oral investigational drug apixaban and Portola’s oral investigational drug betrixaban. The phase 1 study was conducted in 32 healthy volunteers in the United States and showed that PRT4445 was generally safe and well tolerated, and in vitro blood analysis demonstrated that PRT4445 had a rapid (five minute) and sustained (three hour) effect on reversing the activity of that Factor Xa inhibitor.

http://www.portola.com/pdfs/Portola_antidote_press_release_FINAL.pdf