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Critical Care Reviews Newsletter

May 7th 2013



Welcome to the 74th 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 investigations on the changing patterns of mechanical ventilation, effects of sepsis bundle compliance, consequences of azithromycin on cardiovascular death, results of nebulised frusemide in exacerbations of COPD, and a large RCT comparing low target oxygen saturations with higher oxygen saturations in very preterm babies. There are two Cochrane Reviews on routine change of peripheral venous catheters and statins in subarachnoid haemorrhage.

This week's guidelines cover the novel oral anti-coagulants, atrial fibrillation, and unstable angina/non ST elevation myocardial infarction. There are editiorials on radiation risks from imaging and research bias, plus several commentaries, including a couple explaining why the Boston healthcare system managed the marathon bombing so successfully. There is also a study critique on CRASH 2.

Amongst the clinical review articles are two series on intracerebreal haemorrhage and platelet reactivity, plus other papers on point-of-care echo, LVADs, heart failure with preserved ejection fraction, TRALI, PE, factor VIIa in major haemorrhage and two papers on angioedema.

The latest recently made open access articles from the major critical care journals are also included.

The topic for This Week's Papers is intracranial hypertension, with today's Paper of the Day focusing on hyperosmolar therapy.



Journal of the American Medical Association:     Oxygenation

Schmidt and colleagues completed an international randomized, double-blind trial in 1201 premature infants 23 to 27 weeks gestational age, o compare the effects of targeting lower or higher arterial oxygen saturations on the rate of death or disability in extremely preterm infants. Of the 578 infants with adequate data for the primary outcome who were assigned to the lower target range, 298 (51.6%) died or survived with disability compared with 283 of the 569 infants (49.7%) assigned to the higher target range (odds ratio adjusted for center, 1.08; 95% CI 0.85 to 1.37; P = 0.52). The rates of death were 16.6% for those in the 85% to 89% group and 15.3% for those in the 91% to 95% group (adjusted odds ratio, 1.11; 95% CI 0.80 to 1.54; P = 0.54). Targeting lower saturations reduced the postmenstrual age at last use of oxygen therapy (adjusted mean difference, −0.8 weeks; 95% CI, −1.5 to −0.1; P = .03) but did not alter any other outcomes. Conclusion: In extremely preterm infants, targeting oxygen saturations of 85% to 89% compared with 91% to 95% had no significant effect on the rate of death or disability at 18 months.

Full Text:  Schmidt. Effects of Targeting Higher vs Lower Arterial Oxygen Saturations on Death or Disability in Extremely Preterm Infants: A Randomized Clinical Trial (COT trial). JAMA 2013;epublished May 5th


American Journal of Respiratory and Critical care Medicine:     Sepsis Bundles

Miller et al completed a multi-centre observational study to assess the effect on mortality of compliance with a severe sepsis / septic shock management bundle in 4329 adults with severe sepsis or septic shock admitted to ICU from the ED, between January 2004 and December 2010. Overall hospital mortality was 12.1%, declining from 21.2% in 2004 to 8.7% in 2010. All-or-none total bundle compliance increased from 4.9% to 73.4% simultaneously. Mortality declined from 21.7% in 2004 to 9.7% in 2010 among subjects not compliant with one or more bundle element. Regression models adjusting for age, severity of illness, and comorbidities identified an association between mortality and compliance with each of inotropes and/or red cell transfusions, glucocorticoids, and lung protective ventilation. Compliance with early resuscitation elements during the first 3 hours following emergency department admission caused ineligibility, through lower subsequent severity of illness, for these later bundle elements.

Abstract:  Miller. Multicenter Implementation of a Severe Sepsis and Septic Shock Treatment Bundle. Am J Resp Crit Care Med 2013;epublished April 26th


American Journal of Respiratory and Critical care Medicine:     Mechanical Ventilation

To estimate whether mortality in mechanically ventilated patients changed over time, Esteban and colleagues examined data from prospective, cohort studies conducted in 1998, 2004 and 2010 including 18,302 patients receiving mechanical ventilation for more than 12 hours in a 1-month period from 927 units in 40 countries. Ventilatory management changed over time (p<0.001), with increased use of non-invasive positive pressure ventilation (5% in 1998 to 14% in 2010), a decrease in tidal volume [mean 8.8 ml/kg actual body weight (SD 2.1) in 1998 to 6.9 ml/kg (1.9) in 2010], and an increase in applied PEEP [mean 4.2 cmH20 ( 3.8) in 1998 to 7.0 cmH20 (3.0) in 2010]. Crude mortality in the intensive care unit decreased in 2010 compared with 1998 (28% versus 31%; odds ratio 0.87; 95% CI 0.80 to 0.94) despite a similar complication rate. Hospital mortality decreased similarly. After adjusting for baseline and management variables, this difference remained significant (odds ratio: 0.78; 95% CI 0.67 to 0.92). 

Abstract: Esteban. Evolution of Mortality Over Time in Patients Receiving Mechanical Ventilation. Am J Respir Crit Care Med 2013;epublished April 30th


Respiratory Care:     COPD

In a randomized, placebo-controlled, double-blinded trial in 100 patients with an exacerbation of chronic obstructive pulmonary disease, the addition of 40 mg nebulized furosemide to conventional therapy significantly improved severity of dyspnoea, FEV1, pH and PaO2 (p<0.001), but at the expense of a decrease in mean blood pressure and heart rate (p<0.001), when measured one hour post treatment. Furosemide may exert its effects via pulmonary vagal modulation.

Full Text:  Vahedi. The Adjunctive Effect of Nebulized Furosemide in Acute Treatment of Patients with Chronic Obstructive Pulmonary Disease Exacerbation: A Randomized Controlled Clinical Trial. Respir Care 2013;epublished April 30th


New England Journal of Medicine:     Azithromycin

Svanström et al undertook a nationwide historical cohort study from 1997 to 2010 involving Danish adults (18 to 64 years of age) to evaluate the cardiovascular effects of azithromycin and other anti-bacterials drugs. 1,102,050 episodes of azithromycin use were compared with no use of antibiotic agents (matched in a 1:1 ratio according to propensity score, for a total of 2,204,100 episodes) and 1,102,419 episodes of azithromycin use were compared with 7,364,292 episodes of penicillin V use (an antibiotic with similar indications; analysis was conducted with adjustment for propensity score). In comparion with no antibacterial therapy, azithromycin was associated with an increased risk of cardiovascular death (rate ratio 2.85; 95% CI 1.13 to 7.24). The analysis relative to an antibiotic comparator included 17 deaths from cardiovascular causes during current azithromycin use (crude rate, 1.1 per 1000 person-years) and 146 during current penicillin V use (crude rate, 1.5 per 1000 person-years). With adjustment for propensity scores, current azithromycin use was not associated with an increased risk of cardiovascular death, as compared with penicillin V (rate ratio, 0.93; 95% CI, 0.56 to 1.55). The adjusted absolute risk difference for current use of azithromycin, as compared with penicillin V, was −1 cardiovascular death (95% CI −9 to 11) per 1 million treatment episodes.

Abstract: Svanström. Use of Azithromycin and Death from Cardiovascular Causes. N Engl J Med 2013;368:1704-1712


Critical Care:     American Critical Care Outcomes

In a retrospective analysis of hospital mortality in 482,601 ICU admissions from 1988 to 2012 there was a 35% relative decrease in mortality over this period despite an increase in age and severity of illness. Mortality fell by >60% for patients with chronic obstructive pulmonary disease, seizures and surgery for aortic dissection and subarachnoid hemorrhage. Mortality fell by 51%-59% for intracerebral hemorrhage, urosepsis, acute myocardial infarction, surgery for gastrointestinal malignancy, congestive heart failure, and non-urinary tract sepsis; by 41%-50% for intracerebral hemorrhage, stroke, upper GI non-variceal bleeding, viral pneumonia, surgery for multiple-trauma, including the head, surgery for GI perforation, and GI variceal bleeding, and 10%-40% for GI obstruction, acute respiratory distress syndrome, surgery for GI bleeding, cardiac arrest, and head trauma with chest, abdomen, pelvis, or spine injury. The decrease in mortality from 2001 to 2012 was accompanied by an increase in discharge to post-acute care facilities and a decrease in discharge to home.

Full Text:  Zimmerman. Changes in hospital mortality for United States intensive care unit admissions from 1988 to 2012. Critical Care 2013;17:R81


Journal of Critical Care:     Fever

Niven et al performed a systematic review and meta analysis (5 RCTS, n=399) to determine the effect of fever control with antipyretic therapy on the mortality of febrile critically ill adults. The temperature threshold for treatment in the intervention group was typically 38.3°C to 38.5°C, whereas it was usually 40.0°C for controls. Four studies used physical measures and 3 used pharmacologic measures for temperature control. There was no significant heterogeneity among the included studies (I2 = 12.5%, P = 0.3). Fever control had no effect on ICU mortality with a pooled risk ratio of 0.98 (95% confidence interval 0.58-1.63, P = 0.9).

Abstract:  Niven. Antipyretic therapy in febrile critically ill adults: A systematic review and meta-analysis. J Crit Care 2013;28(3):303-310


Neurology:     Guillain-Barre Syndrome

Using prospective data from 4 studies, totalling 527 patients with Guillain-Barré syndrome, the mortality rate was 2.8% at 6 months and 3.9% at 12 months. Eleven patients were admitted to an intensive care unit during the course of disease, but only 7 patients (47%) died in ICU, with risk factors for death being age (p < 0.001), severity of weakness at entry (p = 0.02), mechanical ventilation (p < 0.001), delay from onset of weakness to entry (p = 0.035), and time to peak disability (p = 0.039).

Abstract:  Van den Berg. Mortality in Guillain-Barré syndrome. Neurology 2013;80:1650-1654


Cochrane Reviews

Cochrane Review:     Subarachnoid Haemorrhage

Liu et al performed a systematic review and meta analysis (1 RCT, n=39) to evaluate the effects of cholesterol-reducing agents for improving outcomes in patients with aneurysmal subarachnoid haemorrhage.  In one study comparing simvastatin (80 mg daily; n = 19) with placebo (n = 20) for 14 days, the incidence of delayed ischaemic deficits (secondary outcome) was 26% (5/19) in the simvastatin group versus 60% (12/20) in the placebo group (risk ratio 0.44, 95% CI 0.19 to 1.01, P = 0.05). There were no results from this trial for the primary outcome of death or dependency at six months. The authors conclude that more RCTs are required and that no inferences can be made about the effectiveness and safety of lowering cholesterol in aneurysmal SAH because of insufficient reliable evidence from only one small trial.

Full Text:  Liu. Cholesterol-reducing agents for aneurysmal subarachnoid haemorrhage. Cochrane Database of Systematic Reviews 2013, Issue 4. Art. No.: CD008184


Cochrane Review:     Peripheral Venous Catheter Replacement

Webster et al performed a systematic review and meta analysis (7 RCTs, n=4895) to determine the effect of routine peripheral venous catheter change after 48-72 hours. Routine catheter change (5 trials, n=4806) had no effect on catheter-related bloodstream infection (clinically-indicated 1/2365; routine change 2/2441; risk ratio 0.61, 95% CI 0.08 to 4.68; P = 0.64). There was no difference in phlebitis rates (clinically-indicated 186/2365; 3-day change 166/2441; RR 1.14, 95% CI 0.93 to 1.39), with this result being unaffected by whether infusion through the catheter was continuous or intermittent. When analysed  by number of device days, there remained no differences between groups (RR 1.03, 95% CI 0.84 to 1.27; P = 0.75). One trial assessed all-cause bloodstream infection. There was no difference between the two groups (clinically-indicated 4/1593 (0.02%); routine change 9/1690 (0.05%); P = 0.21). Cannulation costs were lower by approximately AUD 7.00 in the clinically-indicated group (mean difference -6.96, 95% CI -9.05 to -4.86; P ≤ 0.00001).

Full Text:  Webster. Clinically-indicated replacement versus routine replacement of peripheral venous catheters. Cochrane Database of Systematic Reviews 2013, Issue 4. Art. No.: CD007798 



European Heart Journal:     New Oral Anti-Coagulants


Journal of the American College of Cardiology:     Unstable Angina/Non-ST Elevation MI   


Journal of the American College of Cardiology:     Atrial Fibrillation


Study Critique

Journal of Family Practice:     CRASH2



Journal of the American Medical Association:     Boston Marathon Bombing


Annals of Internal Medicine:     Boston Marathon Bombing


New England Journal of Medicine:     Patient Discrimination


Journal of the American Medical Association:     Physician Impairment


Review - Clinical


AJNR American Journal of Neuroradiology:     Neuroimaging in Glycaemic Disorders


AJNR American Journal of Neuroradiology:     Neuroimaging in Cerebral Fat Embolism


AJNR American Journal of Neuroradiology:     Stroke


AJNR American Journal of Neuroradiology:     Brain Imaging in Carbon Monoxide Poisoning


Neurosurgical Focus:     Intracranial Haemorrhage



Cardiology:     Left Ventricular Assist Devices


Cleveland Clinic Journal of Medicine:     Aspirin 


Critical Care Nurses:     Aortic Stenosis



Transfusion Medicine & Hemotherapy:     TRALI


Critical Care Nurses:     Pulmonary Embolism



Transfusion Medicine:     Factor VIIa in Major Haemorrhage


Transfusion Medicine & Hemotherapy:     Platelet Function Testing


Thrombosis & Haemostasis:     Platelet Reactivity



American Journal of Critical Care:     Sepsis Guidelines



New England Journal of Medicine:     Injuries



Biologics: Targets and Therapy:     Hereditary Angioedema


Cleveland Clinic Journal of Medicine:     Hereditary Angioedema


Recently Made Open Access Articles from Major Journals


American Journal of Respiratory and Critical Care Medicine:  




Critical Care:


British Journal of Anaesthesia:


Anesthesia & Analgesia:


Acta Anaesthesiologica Scandinavica: 


Position Statement

American Journal of Respiratory and Critical Care Medicine:     Role of Clinical Research in Practice


American Journal of Respiratory and Critical Care Medicine:     Interstitial Lung Disease



American Journal of Respiratory and Critical Care Medicine:    

Critical Care & Resuscitation:     Nutrition




British Journal of Anaesthesia:


Anaesthesia & Analgesia:




Canadian Journal of Anaesthesia:

Review - Basic Science

BMC Medicine:     Evolutionary Medicine


Medical Gas Research:     Hydrogen Sulphide



I hope you find these brief summaries and links useful.

Until next week