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Critical Care Reviews Newsletter

March 3rd 2013



Welcome to the 65th 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 probably the biggest Newsletter to date, bringing you 8 research studies, 6 Cochrane Reviews, 2 guidelines, 3 editorials, 3 commentaries, 4 study critiques and a massive 82 review articles, including 41 excellent update papers from the World Federation of Societies of Anaesthesiologists.

This week's research studies include studies on prone positioning in obese patients, pathological analysis of cell injury in sepsis-induced organ failure, and further bad news for proponents of colloids, with a negative meta analysis of albumin use in sepsis and yet another report of harm with starches, this time with tetrastarch. The Cochrane Reviews continue the colloid theme and following a comprehensive review of all types of colloid, state it is difficult to justify their use clinically. The Cochrane Group also review pulmonary artery catheters and protective ventilation in ARDS. This week's guidelines are on peripheral arterial disease and implantable cardioverter - defibrillators and cardiac resynchronization therapy.

Amongst the clinical review articles are interesting papers on brian death, sepsis, and nutrition. If it's all a bit too much, try Lemmingaid, a much needed dose of humour from the Journal of The Intensive Care Society. If it's popular I'll add the rest in the series. The New England Journal of Medicine have published a set of 4 articles on the ever expanding open access publication movement, of which Critical Care Reviews is a clear supporter.

Based on a supplement in Critical Care, the topic for This Week's Papers is the pulmonary artery catheter, starting with a reappraisal of its use in tomorrow's Paper of the Day.



Intensive Care Medicine:     Tetrastarch

Patel and colleagues performed a systematic review and meta-analysis to assess the effect of fluid resuscitation with 6% tetrastarch in comparison with other non-HES fluids in adults with severe sepsis. Six randomized controlled trials (n=3,033) were included, with a median tetrastarch dose of 37 ml/kg. In comparison with crystalloids, there was a 13% relative increase in 90 day mortality (RR 1.13; 95% CI 1.02-1.25; p=0.02), with a number needed to harm of 28.8 (95% CI 14.6–942.5).Tetrastarch exposure was also associated with renal replacement therapy (p = 0.01; NNH 15.7) and allogeneic transfusion support (p = 0.001; NNH 9.9). Conclusion: Fluid resuscitation with 6% tetrastarch is associated with increased mortality, need for renal replacement therapy and red cell transfusion in adults with severe sepsis.

Abstract: Patel. Randomised trials of 6% tetrastarch (hydroxyethyl starch 130/0.4 or 0.42) for severe sepsis reporting mortality: systematic review and meta-analysis. Intensive Care Med 2013;epublished ahead of print


American Journal of Respiratory and Critical Care Medicine:     Sepsis-Induced Organ Failure

To evaluate the degree of sepsis-induced cardiomyocyte and renal tubular cell injury and death, using light and electron microscopy and immunohistochemical staining for markers of cellular injury and stress, Takasu and colleagues compared rapid postmortem cardiac and renal analysis in 44 septic patients with control hearts from 12 transplant and 13 brain-dead patients and control kidneys from 20 trauma patients and 8 patients with cancer. They determined cell death is rare in sepsis-induced cardiac dysfunction, but cardiomyocyte injury occurs. Renal tubular injury is common in sepsis but presents focally; most renal tubular cells appear normal. Conclusion: In sepsis, the degree of cell injury and death does not account for severity of organ dysfunction.

Abstract:  Takasu. Mechanisms of Cardiac and Renal Dysfunction in Patients Dying of Sepsis. Am J Respir Crit Care Med. 2013;187:509-517


Journal of Hepatology:     Liver Transplantation in Europe    

Using data from 145 centres in 26 European countries, Karam et al detailed the profile of liver transplantation in Europe. Approximately 5,800 liver transplantations are performed annually across the continent, with France perfoming the most transplantations over the past 40 years (16,366). Over the last 10 years (1999-2009), the main indications, and 5 year graft/patient survial rates, were: viral cirrhosis 23% (56% / 74%); alcoholic cirrhosis 20% (83% / 86%); cryptogenic cirrhosis 4% (79% / 83%); autoimmune cirrhosis 2% (84% / 88%); cholestatic disease 10% (83% / 89%); acute hepatic failure 7% (70% / 76%) and congenital biliary disease 4% (84% / 90%); plus others.

Abstract:  Karam. Evolution of indications and results of liver transplantation in Europe. A report from the European Liver Transplant Registry (ELTR). J Hepatol 2012;57(3):675-88


Critical Care:     Diabetic Glycaemic Control

Krinsley et al completed a retrospective study of 44,964 patients admitted to 23 intensive care units (ICU's) from 9 countries, between February, 2001 and May, 2012 to analyze the independent association of blood glucose with mortality. In non-diabetic patients, mean blood glucose between 80-140 mg/dL was independently associated with reduced mortality and mean blood glucose greater than 140 mg/dL with increased mortality. In diabetics, mean blood glucose of 80-110 mg/dL was associated with increased mortality and mean blood glucose of 10-180 mg/dL with decreased risk of mortality. Hypoglycemia (blood glucose < 70 mg/dL) was independently associated with increased risk of mortality among both diabetics and non-diabetics. Increased glycemic variability, defined as a coefficient of variability greater than 20%, was independently associated with increased mortality in non-diabetics. Derangements of more than 1 domain of glycemic control had a cumulative association with mortality, especially for patients without diabetes. Conclusion: In a large retrospective study, dysglycaemia is associated with increased mortality in the critically ill; diabetics may benefit from a higher blood glucose level.

Full Text:  Krinsley. Diabetic status and the relationship of the 3 domains of glycemic control to mortality in critically ill patients: an international multi-center cohort study. Critical Care 2013;17:R37


Chest:     Prone Positioning

To determine the potential role prone positioning may have in obese patients with ARDS, De Jong and colleagues undertook a case control study comparing outcomes between 33 morbidly obese patients with ARDS  (BMI ≥ 35 kg/m2) and 33 matched non-obese (BMI < 30 kg/m2) ARDS patients.  Median (range) durations of prone positioning were similar {obese 9 (6-11) hours versus non-obese 8(7-12) hours; P=0.28}.  PaO2/FiO2 ratio increased significantly more in obese patients (from 118±43 to 222±84 mmHg) than in non-obese patients (from 113±43 mmHg to 174±80mmHg; P=0.03). Complications, length of mechanical ventilation, ICU stay and nosocomial infections did not differ, but mortality at 90 days was significantly lower in obese patients (27 vs 48%, P<0.05). Conclusion:  Prone positioning appears to be safe in obese patients with ARDS, and may benefit this group more than non-obese patients.

Abstract:  De Jong. Feasibility and effectiveness of prone position in morbidly obese ARDS patients: a case-control clinical study. Chest 2013;epublished February 28th


Intensive Care Medicine:     Renal Replacement Therapy

Schneider and colleagues undertook a systematic review and meta analysis to compare the rate of dialysis dependence among severe acute kidney injury survivors according whether continuous renal replacement therapy (CRRT) or intermittent haemodialysis (IHD) was the initial mode of renal replacement therapy. 23 studies were identified: seven randomized controlled trials (RCTs) and 16 observational studies involving 472 and 3,499 survivors, respectively. Pooled analyses of RCTs showed no difference in the rate of dialysis dependence among survivors (relative risk, RR 1.15 [95 % CI 0.78–1.68], I2 = 0 %). However, pooled analyses of observational studies suggested a higher rate of dialysis dependence among survivors who initially received IHD as compared with CRRT (RR 1.99 [95 % CI 1.53–2.59], I2 = 42 %). Conclusion: Observational, but not interventional, data suggests initial IHD therapy may be associated with prolonged dependence on renal replacement therapy.

Abstract:  Schneider. Choice of renal replacement therapy modality and dialysis dependence after acute kidney injury: a systematic review and meta-analysis. Intensive Care Med 2013;epublished February 27th


PLoS Medicine:     Out-of-Hospital Cardiac Arrest

Hagihara conducted a prospective, non-randomized, observational study using national data of all 531,854 patients with out-of-hospital cardiac arrest (OHCA) from 2005 through 2009 in Japan to assess the effect of prehospital use of Ringers Lactate on outcome. Among propensity-matched patients, compared with those who did not receive pre-hospital intravenous fluids, pre-hospital use of LR solution was associated with an increased likelihood of ROSC before hospital arrival (OR adjusted for all covariates 1.239; 95% CI 1.146–1.339; p<0.001), but with a reduced likelihood of 1-month survival with minimal neurological or physical impairment (cerebral performance category 1 or 2, OR adjusted for all covariates 0.764, 95% CI 0.589–0.992; p = 0.04); and overall performance category 1 or 2, OR adjusted for all covariates 0.746, 95% CI 0.573–0.971; p = 0.03). There was no association between prehospital use of LR solution and 1-month survival (OR adjusted for all covariates 0.96, 95% CI 0.854–1.078). Conclusion: In patients with out-of-hospital cardiac arrest, pre-hospital use of Ringers Lactate was not associated with improved outcomes.

Full Text:  Hagihara. Prehospital Lactated Ringer's Solution Treatment and Survival in Out-of-Hospital Cardiac Arrest: A Prospective Cohort Analysis. PLoS Med 2013;10(2):e1001394


Journal of the Intensive Care Society:     Human Albumin Solution

Leitch and colleagues performed a meta-analysis of randomised controlled trials comparing the effect of human albumin solution with other fluid resuscitation on mortality in patients with severe sepsis. Nine trials (n=1,435) were included. Albumin was not associated with a decrease in mortality (relative risk 0.90, 95% CI 0.79-1.02), although most trials reported to date are small and of variable methodological quality. Soon to be published studies from Italy (Albumin Italian Outcome Sepsis, ALBIOS study) and France (Early Albumin Resuscitation in Septic Shock trial, EARSS) were not included but have also reported negative results to date.

Full Text: Leitch. Human albumin solution resuscitation in severe sepsis and septic shock. JICS 2013;14(1):45-52


Cochrane Review

Cochrane Review:     Colloids versus Crystalloids for Fluid Resuscitation

In an updated systematic review and meta analysis, Perel and colleagues compared crystalloids with colloids for fluid resuscitation in the critically ill.

Colloids compared to crystalloids:Albumin or plasma protein fraction - 24 trials reported data on mortality, including a total of 9920 patients. The pooled risk ratio (RR) from these trials was 1.01 (95% confidence interval (CI) 0.93 to 1.10). When we excluded the trial with poor-quality allocation concealment, pooled RR was 1.00 (95% CI 0.92 to 1.09).

Hydroxyethyl starch: 25 trials compared hydroxyethyl starch with crystalloids and included 9147 patients. The pooled RR was 1.10 (95% CI 1.02 to 1.19).

Modified gelatin: 11 trials compared modified gelatin with crystalloid and included 506 patients. The pooled RR was 0.91 (95% CI 0.49 to 1.72). (When the trials by Boldt et al were removed from the three preceding analyses, the results were unchanged.) Dextran - nine trials compared dextran with a crystalloid and included 834 patients. The pooled RR was 1.24 (95% CI 0.94 to 1.65).

Colloids in hypertonic crystalloid compared to isotonic crystalloid:  Nine trials compared dextran in hypertonic crystalloid with isotonic crystalloid, including 1985 randomised participants. Pooled RR for mortality was 0.91 (95% CI 0.71 to 1.06).

Conclusion:  The authors conclude that as colloids are more expensive than crystalloids, offer no benefit over crystalloids, and hydroxyethyl starches are associated with increased mortality, the ongoing clinical use of colloids is difficult to justify.

Perel. Colloids versus crystalloids for fluid resuscitation in critically ill patients. Cochrane Database of Systematic Reviews 2013;2:CD000567


Cochrane Review:     Pulmonary Artery Catheters

Rajaram et al performed a systematic review and meta analysis, including 13 studies (n=5686), comparing management with and without a pulmonary artery catheter in critically ill adults. The pooled risk ratio (RR) for mortality for 5 studies of general intensive care patients was 1.02 (95% CI 0.96 - 1.09) and for 8 studies of high-risk surgery patients the RR was 0.98 (95% CI 0.74 to 1.29). In 5 of the studies in high-risk surgery patients which evaluated the effectiveness of pre-operative optimization, there was no difference in mortality. PAC did not affect general ICU length of stay (reported by four studies) or hospital length of stay (reported by nine studies). Four studies, conducted in the United States (US), reported costs based on hospital charges billed, which on average were higher in the PAC groups. Two of these studies qualified for analysis and did not show a statistically significant hospital cost difference (mean difference USD 900, 95% CI -2620 to 4420, P = 0.62). Conclusion:  The use of a pulmonary artery catheter was not associated with decreased mortality, general ICU or hospital length of stay, or cost for adult patients in intensive care; although whether this is due to the monitor or therapeutic strategy employed is unclear.

Full Text: Rajaram. Pulmonary artery catheters for adult patients in intensive care. Cochrane Database Syst Rev. 2013 Feb 28;2:CD003408


Cochrane Review:     High-Frequency Oscillation

In an "updated" review (although already outdated as it was performed in 2011, before the recent OSCAR and OSCILLATE trials were reported, but only published now), Sud and colleagues determined in 8 randomized controlled trials (n=433) that high frequency oscillation was a promising treatment for ALI and ARDS prior to the uptake of current lung protective ventilation strategies. Conclusion: This meta analysis is outdated and the results obsolete.

Full Text:  Sud. High-frequency ventilation versus conventional ventilation for treatment of acute lung injury and acute respiratory distress syndrome. Cochrane Database Syst Rev 2013 Feb 28;2:CD004085


Cochrane Review:     Lung Protective Ventilation

In an updated review (no new data found) Petrucci and colleagues performed a systematic review and meta analysis (six trials, n = 1297) comparing protective ventilation with non-protectice ventilation in ALI/ARDS.  Lung-protective ventilation was associated with a 26% relative decrease in mortality at 28 days (95% CI 0.61 - 0.88) and a 20% relative decrease in hospital mortality (95% CI 0.69 - 0.92). Overall mortality was not significantly different if a plateau pressure less than or equal to 31 cm H2O in the control group was used (RR 1.13, 95% CI 0.88 - 1.45). There was insufficient evidence for morbidity and long-term outcomes. Conclusion: Lung-protective ventilation is associated with significant improvements in mortality and length of hospital stay in ALI/ARDS patients.

Full Text:  Petrucci. Lung protective ventilation strategy for the acute respiratory distress syndrome. Cochrane Database Syst Rev 2013 Feb 28;2:CD003844


Cochrane Review:     Partial Liquid Ventilation in Paediatrics

In a systematic review and meta analysis evaluating the eficacy of partial liquid ventilation in paediatric lung injury, only one study enrolling 182 patients (reported as an abstract in conference proceedings) was identified and found eligible for inclusion; the authors reported only limited results. The trial was stopped prematurely and was, therefore, under-powered to detect any significant differences and at high risk of bias. The only available outcome of clinical significance was 28-day mortality. There was no statistically significant difference between groups, with a relative risk for 28-day mortality in the partial liquid ventilation group of 1.54 (95% confidence interval 0.82 to 2.9). Conclusion: There is no evidence from RCTs to support or refute the use of partial liquid ventilation in children with acute lung injury or acute respiratory distress syndrome

Full Text:  Kaushal. Partial liquid ventilation for the prevention of mortality and morbidity in paediatric acute lung injury and acute respiratory distress syndrome. Cochrane Database Syst Rev 2013 Feb 28;2:CD003845


Cochrane Review:     GABA Receptors for Acute Stroke

Liu and Wang performed a systematic review and meta analysis to determine the efficacy and safety of GABA receptor agonists in the treatment of acute stroke. Five trials (n= 3838) with a low risk of bias were identified. Four trials measured death and dependency at three months in chlormethiazole versus placebo without significant difference (risk ratio (RR) 1.03, 95% CI 0.95 - 1.11). One trial measured this outcome between diazepam and placebo (RR 0.94, 95% CI 0.82 - 1.07). In the subgroup analysis of total anterior circulation syndrome, a higher percentage of functional independence was found in the chlormethiazole group (RR 1.33, 95% CI 1.09 - 1.64). The frequent adverse events related to chlormethiazole were somnolence (RR 4.56, 95% CI 3.50 - 5.95) and rhinitis (RR 4.75, 95% CI 2.67 - 8.46). Conclusion:  The evidence does not support the use of GABA receptor agonists (chlormethiazole or diazepam) for the treatment of patients with acute ischemic or hemorrhagic stroke

Liu. Gamma aminobutyric acid (GABA) receptor agonists for acute stroke. Cochrane Database of Systematic Reviews 2013;2:CD009622



Circulation:     Peripheral Arterial Disease


Journal of the American College of Cardiology:     Implantable Cardioverters-Defibrillation



Journal of the Intensive Care Society:     Brain Death


Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine:     Publishing Trial Protocols


Respiratory Care:     Recruitment


Antimicrobial Resistance and Infection:     Chennai Declaration


Emergency Medicine News:     Carbapenam Resistant Klebsiella Pneumonia


Study Critiques

Journal of the Intensive Care Society:     Ultrasound-Guided Subclavian Vein Cannulation


Journal of the Intensive Care Society:     6S Study


Journal of the Intensive Care Society:     Citrate Anticoagulation for CRRT


Journal of the Intensive Care Society::     Tranexamic Acid


Review - Clinical


Critical Care:     Mobilisation


Journal of the Intensive Care Society:     Benzodiazepine Administration


Journal of the Intensive Care Society:     Subarachnoid Haemorrhage


Journal of the Intensive Care Society:     Delirium


Neuroscience Journal:    Incidental Findings in Neuroimaging



Perioperative Medicine:     Anaerobic Threshold


Indian Journal of Endocrinology and Metabolism:     Natriuretic Hormones


Journal of Anesthesia and Clinical Research:     Cirrhosis-Associated Cardiomyopathy


Journal of the American College of Cardiology:     Heart Team



Journal of the Intensive Care Society:     Pulmonary Embolism


Annals of Medical and Health Sciences Research:     Postoperative Pulmonary Oedema


Revista da Associação Médica Brasileira:     Viral Community-Acquired Pneumonia



Nutrition in Intensive Care Medicine: Beyond Physiology:     Nutrition



Clinical Liver Disease:     Hepatitis B


Liver International:     Liver Transplantation



Nephrology:     Melioidosis associated Acute Kidney Injury



Cleveland Clinic Journal of Medicine:     Sepsis


Virology Journal:     Novel Coronavirus


Therapeutic Advances in Infectious Diseases:     Febrile Neutropaenia


Therapeutic Advances in Infectious Diseases:     Clostridium Difficile


Therapeutic Advances in Infectious Diseases:     Community-Acquired Pneumonia


Journal of Basic & Clinical Medicine:     Procalcitonin


Indian Journal of Medical Science:     New Delhi Metallo-Beta-Lactamase


Clinical Infectious Diseases:     Fungal Infections



Marine Drugs:     Jellyfish Stings


Organ Transplantation

Clinical and Translational Medicine:     Organ Transplantation


Ethics / End-of-Life

Journal of the Intensive Care Society:     Assisted Suicide


Cleveland Clinic Journal of Medicine:     End-of-Life


Respiratory Care:     Apnoea Testing


PLoS Biology:     Animal Experiments



Review - Basic Science

Circulation Research:     Therapeutic Transdifferentiation


International Journal of Vascular Medicine:     MicroRNAs in Vascular Biology


Journal of Hematology & Oncology:     Mitochondrial Reactive Species


Cardiovasc Research:     Proteomics


Review - Non-Clinical

New England Journal of Medicine:     Open Access Publication


and a bit of humour:

Journal of the Intensive Care Society:     Lemmingaid


World Federation of Societies of Anaesthesiologists:     Update in Anaesthesia 2012


General Principles




General Care

















I hope you find these brief summaries and links useful.

Until next week