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Critical Care Reviews Newsletter

January 6th 2012



Welcome to the 57th 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 yet another paper demonstrating worse outcomes with a higher red cell transfusion threshold, this time in the setting of upper GI bleeding. The latest negative study on MARS has been published, as well as the latest negative compound tested for acute heart failure. On a more positive note, a prospective study on ECMO provides further support for the use of this therapy and sonothrombolysis appears to have a possible beneficial effect in acute cerebral infarction, although study numbers were low.

This week's guideline is from the American College of Cardiology Foundation, on the generation of guidelines.

Amongst the clinical review articles are papers on ICU acquired weakness, ventricular assist devices, capnography, haemorrhagic liver injury, peri-operative diabetic management, anti-coagulants, candida, mitochondrial therapy and do-not-resuscitate orders. A non-clinical review article looks at the future of the anaesthesia profession.

The topic for This Week's Papers is nosocomial infections, starting with a paper on clostridium difficile in tomorrow's Paper of the Day.



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New England Journal of Medicine:     Upper Gastrointestinal Haemorrhage

Villanueva et al performed a randomized study comparing the efficacy and safety of a restrictive transfusion strategy (Hb <7g/dL) with those of a liberal transfusion strategy (Hb<9g/dL) in 921 patients with severe acute upper gastrointestinal bleeding. More patients in the restrictive group did not receive a transfusion (n=225/51% versus n=65/15%, p<0.001). The restrictive practice was associated with numerous benefits, including increased probability of survival (95% versus 91%; hazard ratio for death 0.55; 95% CI: 0.33-0.92; p=0.02); decreased rebleeding (10% versus 16%, p=0.01) and adverse events (40% versus 48%, p=0.02). In subgroup analysis, restrictive transfusion was associated with improved probability of survival in patients with cirrhosis and Child–Pugh class A or B disease (HR 0.30; 95% CI 0.11 to 0.85), but not in those with cirrhosis and Child–Pugh class C disease (HR 1.04; 95% CI 0.45 to 2.37) or bleeding associated with a peptic ulcer (HR 0.70; 95% CI 0.26 to 1.25). Liberal transfusion was associated with an increase in portal-pressure gradient at 5 days (p=0.03). Conclusion: In a large multi-centre randomized study in upper GI bleeding, red cell transfusion based on a haemoglobin threshold of 7g/dL, was associated with improved mortality, reduced rebleeding rates and reduced adverse events than a transfusion policy based on a 9g/dL threshold.

Abstract:  Villanueva. Transfusion Strategies for Acute Upper Gastrointestinal Bleeding. N Engl J Med 2013;368:11-21


Hepatology:     Extracorporeal Albumin Dialysis

Bañares and colleagues performed a prospective, randomized controlled trial in 189 patients with acute-on-chronic liver failure, comparing extracorporeal albumin dialysis (molecular adsorbent recirculating system (MARS), up to ten 6-8 hours sessions, n=95) or to standard therapy (n=94). A number of patients were excluded for protocol violations. Both groups were similar at baseline. There was no difference in  28-day survival, 60% vs 59%. After adjusting for confounders, MARS had no effect on survival (odds ratio: 0.87; CI 95 % 0.44-1.72). Severe adverse events were similar. Conclusion: In this study, MARS did not improve survival in acute-on-chronic liver failure, but did demonstrate a significant dialysis effect (lower creatinine, p=0.02 and lower bilirubin p=0.001). 

Abstract: Bañares. Extracorporeal albumin dialysis with the molecular adsorbent recirculating system in acute-on-chronic liver failure: The RELIEF trial. Hepatology 2012;epublished ahead of print


European Heart Journal:     Acute Heart Failure

Erdmann and colleagues completed a placebo-controlled, phase IIb study evaluating the haemodynamic effect and safety of cinaciguat, a novel soluble guanylate cyclase activator, added to standard therapy in 139 patients with acute decompensated heart failure.  Cinaciguat was titrated for 8 h and maintained for 16–40 h (starting dose: 100 μg/h). At 8 h, cinaciguat was associated with greater decreases in mean PCWP (decrease of 7.7 mmHg from a baseline of 25.7 ± 5.0 mmHg versus a decrease of 3.7 mmHg from a baseline of 25.0 ± 5.3 mmHg; p < 0.0001), mean right atrial pressure (decrease of 2.7 mmHg from a baseline of 12.4 ± 5.3 mmHg versus a decrease of 0.6 mmHg from a baseline of 11.8 ± 4.9 mmHg; p= 0.0019) and pulmonary and systemic vascular resistance and mean arterial pressure (all p < 0.0001 vs. placebo) in addition to an increase in cardiac index (p < 0.0001). Cinaciguat was associated with a larger decrease in systolic blood pressure, falling by 21.6 ± 17.0 mmHg in comparison with a decrease of 5.0 ± 14.5 mmHg with placebo. There was a greater incidence of adverse effects with cinaciguat; 71% versus 45%. No adverse effects on the 30-day mortality were seen; however, the trial was stopped prematurely due to an increased occurrence of hypotension at cinaciguat doses ≥200 µg/h. Conclusion:  Cinaciguat therapy was associated with greater decreases in pulmonary and systemic venous and arterial pressures than placebo. Significant systemic arterial hypotension necessitated termination of this study.

Full Text:  Erdmann. Cinaciguat, a soluble guanylate cyclase activator, unloads the heart but also causes hypotension in acute decompensated heart failure. Eur Heart J 2013;34:57-67


Acta Anaesthesiologica Scandinavica:     ECMO

Lindskov et al present data from a 14 year prospective observational study (1997-2011) on 124 Scandanavian patients treated with ECMO for severe respiratory failure. The treatment was based mainly on venous-venous ECMO and centrifugal pumps. The median patient age was 45 years (range 16–67) and the median Murray score was 3.7 (2.5–4.0). One hundred and six (85%) of the patients were retrieved from referring hospitals on ECMO. The median duration of the ECMO was 215 (1–578) h. Ninety-seven (78%) of the patients could be weaned from ECMO. A total of 88 (71%) were discharged alive to the referring hospitals. High SAPS-II, SOFA and Murray scores were associated with a high mortality. Conclusion: ECMO therapy was associated with a high survival rate in this prospective observational study of patients with severe respiratory failure.

Abstract:  Lindskov. Extracorporeal membrane oxygenation in adult patients with severe acute respiratory failure. Acta Anaesthesiologica Scandinavica 2012; epublished December 28th


Stroke:    Sonothrombolysis for Acute Ischemic Stroke

Ricci and colleagues performed a systematic review and meta analysis of studies evaluating the effects of ultrasound to enhance the lysis of intra-arterial thrombi in acute ischemic stroke during systemic intravenous thrombolysis with tissue plasminogen activator (tPA). Five studies (n=233) were included, with 3 studies using transcranial color-coded duplex, and 2 using transcranial color doppler. Sonothrombolysis was associated with a statistically significant difference for the primary outcome of death or disability at 3 months; (n=206; OR: 0.50; 95% CI: 0.27–0.91), failure to recanalize (n=230; OR: 0.28; 95% CI, 0.16–0.50) . There was no effect on mortality (n=206; OR: 1.00; 95% CI, 0.46–2.16) or increasing cerebral hemorrhages (n=233; OR: 2.35; 95% CI: 0.95–5.80). Conclusion: Sonothrombolysis was associated with an improvement in the combined primary outcome of death or disability at 3 months, without an increase in intracranial haemorrhage.

Full Text: Ricci. Sonothrombolysis for Acute Ischemic Stroke. Stroke 2013;epublished January 3rd



Circulation:     Guideline Methodology



 Intensive Care Medicine:     Tidal Volume


Review - Clinical


Anesthesiology:     ICU Acquired Weakness


Journal of Neurosciences in Rural Practice



Journal of American College of Cardiology:     Myocardial Recovery


Journal of American College of Cardiology:     Acute Coronary Syndrome


Journal of the American College of Cardiology:     Ventricular Assist Devices


Interactive Cardiovascular Thoracic Surgery:    Anticoagulation with Intracranial Bleed


Interactive Cardiovascular Thoracic Surgery:    Mechanical Support post Cardiac Surgery


The Journal of Herat and Lung Transplantation:     Axial and Centrifugal Continuous-Flow Rotary Pumps


JACC Cardiovascular Interventions:     Uncontrolled Hypertension


Cleveland Clinic Journal of Medicine:     Advanced Heart Failure Therapy


Cleveland Clinic Journal of Medicine:     Short QT Interval


European Radiology:     Cardiac MR


Annals of Cardiac Anaesthesia:     Anaesthesia for Off-Pump CABG



Anesthesiology:     Capnography


Pulmonary Medicine:     Pulmonary Effects of Heart Failure



Journal of Medical Nutrients and Pharmaceuticals:     Peri-Operative Diabetic Management


European Journal of Clinical Nutrition:     Water Requirements



Annals of Hepatology:     N-Acetylcysteine in Non-Paracetamol induced-Acute Liver Failure


Journal of Anesthesia:     Liver in Haemorrhagic Shock


Journal of Postgraduate Medicine:     Anticoagulants


Laboratory Medicine:     Haemostasis


Laboratory Medicine:     Complications of Blood Transfusion


Thrombosis Journal:     Venous Thromboembolism



PLoS Pathogens:     Candida


EMBO Molecular Medicine:     Studying Sepsis


Frontiers in Immunology:     C5a and C5a receptors in sepsis



Journal of Critical Care:     DNR



British Journal of Haematology:     Allergic Response


Journal of Cerebral Blood Flow & Metabolism:     Mitochondrial Therapuetics


Review - Non-Clinical

Canadian Journal of Anesthesia:     Anaesthesia



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Until next week