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Newsletter 123 / April 13th 2014

Welcome

 

Hello

Welcome to the 123rd 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, guidelines, commentaries and editorials from hundreds of clinical and scientific journals.

This week's highlighted research studies include randomized controlled trials on thrombolysis for intermediate-risk pulmonary embolism, spironolactone for heart failure with preserved left ventricular ejection fraction, hypocaloric nutrition, nutrition in ARDS, and metformin post STEMI; meta analyses address extracorporeal life support for acute respiratory failure, vasopressin during CPR, corticosteroids in ARDS, and oseltamivir for influenza; observational studies focus on propofol versus benzodiazepine sedation, venous thromboembolism prophylaxis, psychological and functional outcomes post ICU, and the incidence of MRSA infections in the USA. Additional studies include investigations into high flow nasal cannuale, timing of renal replacement therapy, VRE, β blockers in asthma, central line-associated bloodstream infections, protective ventilation in the non-injured lung and steroids for severe community acquired pneumonia.

This month's Cochrane reviews include two new articles on anticoagulation in non-valvular AF and cerebral CT in brain death, plus updated papers on opioid withdrawal, ischaemic stroke, liver transplantation, perioperative monitoring, fluids in bleeding, and anticoagulation in heart failure with sinus rhythm.

This week's guidelines look at appendicitis and fungal infections in burns patients, while editorials address cooling post cardiac arrest, stem cell therapy, ischaemic stroke, electrophysiological testing and ARDS research. Commentaries focus on medicaid and physician-led accountable care. There are two case reports on reversible cerebral vasoconstriction syndrome and explosive trauma.

Amongst the clinical review articles are papers on stroke, myasthenic crisis, elevated troponin, ECMO monitoring, respiratory complications of rheumatoid disease, β blockers in portal hypertension, sodium-rich crystalloids, acquired haemophilia A, melioidosis and high-dose insulin therapy. There are also 9 papers from the Annual Update in Intensive Care and Emergency Medicine 2014.

One basic science review articles discusses survival analysis of time-to-event data, while non-clinical reviews explore publishing a scientific manuscript and guideline development.

The topic for This Week's Papers is pulmonary embolism, starting with a paper on cmanagement dilemmas in tomorrow's Paper of the Day.

In other news, e-Learning for Heathcare have released a free new resource on intensive care echo and lung ultrasound. Both a UK NHS email address and GMC number may be required to access this.

 

Critical Care Reviews Meeting 2015

Planning for the the next Critical Care Reviews Meeting is well underway, with some fantastic speakers lined up. Further details to emerge in the following weeks.

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Research

Randomised Controlled Trials

Meyer and colleaguese compared tenecteplase plus heparin with placebo plus heparin in 1,006 normotensive patients with intermediate-risk pulmonary embolism, identified by right ventricular dysfunction (on echo or CT) and myocardial injury (positive troponin I or T), and found:

  1. tenecteplase plus heparin was associated with
    • reduced rate of death or haemodynamic decompensation (1° outcome)
      • 2.6% (13/506) versus 5.6% (28/499) 
      • odds ratio 0.44; 95% CI 0.23 to 0.87; P=0.02
    • increased
      • extracranial bleeding
        • 6.3% versus 1.2%  (P<0.001)
      • stroke
        • 2.4% versus 0.2%  (P=0.003)
        • hemorrhagic stroke - 10 patients versus 1 patient
  2. no difference in death by
    • day 7
      • tenecteplase plus heparin group: 1.2% versus heparin group 1.8% (P=0.42)
    • day 30
      • tenecteplase plus heparin group: 2.4% versus heparin group 3.2% (P=0.42)

Pitt and colleagues compared spironolactone (15 to 45 mg daily) with placebo in 3,445 patients with symptomatic heart failure and preserved left ventricular ejection fraction, and found over a median 3.3 year follow up:

  1. no difference in a composite of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for the management of heart failure (1° outcome)
    • spironolactone 18.6% versus placebo 20.4%
    • hazard ratio 0.89; 95% CI 0.77 to 1.04; P=0.14
      • of the 1° outcome components, only hospitalization for heart failure had a significantly lower incidence in the spironolactone group
        • 12.0% versus 14.2%; HR 0.83, 95% CI 0.69 to 0.99, P=0.04
  2. spironolactone therapy was associated with
    • higher rate of hyperkalemia
      • 18.7% vs. 9.1%
    • a lower rate of hypokalemia
      • 16.2% vs. 22.9%
    • doubling of serum creatinine
      • 10.2% vs. 7.0%
  3. no significant differences in the
    • incidence of serious adverse events
    • serum creatinine level of 265 μmol/l (3.0 mg/dl) or higher
    • dialysis

In a pilot study, Petros and colleagues compared normocaloric feeding (100% daily energy expenditure) with hypocaloric feeding (50% daily energy expenditure) in 100 critically ill patients requiring artificial nutrition for at least 72 hours, and found:

  1. basic data
    • 66 males and 34 females
    • mean age of 65.8 ± 11.6 years
  2. a significant difference in delivered nutrition
    • normocaloric group 19.7 ± 5.7 kcal/kg versus hypocaloric group 11.3 ± 3.1 kcal/kg (P = 0.0001)
  3. normocaloric feeding was associated with
    • increased
      • insulin demand
      • gastrointestinal intolerance
    • decreased nosocomial infections 
      • 11.1% versus 26.1%
  4. no difference in mortality
    • ICU
      • normocaloric group 22.2% versus hypocaloric group 21.7% (p>0.05)
    • hospital mortality
      • normocaloric group 31.5% versus hypocaloric group 37.0% (P = 0.67)

Braunschweig and colleagues compared intensive medical nutrition therapy (provision of >75% of estimated energy and protein needs per day via EN and adequate oral diet) with standard nutrition support care (standard EN and ad lib feeding) in 78 patients from diagnosis of acute lung injury to hospital discharge, and found:

  1. the trial was stopped early for increased mortality with intensive medical nutrition therapy
    • 40% vs 16%, P = 0.02
    • hazard of death 5.67, P = 0.001
  2. at baseline
    • no differences between groups for
      • age, body mass index, disease severity, white blood cell count, glucose, C-reactive protein, energy or protein needs
  3. intensive medical nutrition therapy was associated with a higher percentage per day of
    • estimated energy
      • 84.7% versus 55.4%, P < 0.0001
    • protein needs
      • 76.1 versus 54.4%, P < 0.0001
  4. there were no differences in
    • length of
      • mechanical ventilation
      • stay
        • hospital
        • ICU stay
      • infections

Lexis and colleagues compared metformin hydrochloride (500 mg, n = 191) with placebo (n = 189) twice daily for 4 months in 380 non-diabetic patients with ST elevation myocardial infarction treated with percutaneous coronary intervention, and found at 4 months:
  1. no difference in
    • left ventricular ejection fraction (assessed by MRI)
      • metformin group 53.1% (95% CI 51.6% to 54.6%) versus placebo group 54.8% (95% CI, 53.5% to 56.1%) (P = 0.10)
    • NT-proBNP
      • metformin group 167 ng/L (IQR 65 to 393 ng/L) versus placebo group 167 ng/L (IQR 74 to 383 ng/L) (P = 0.66)
    • major adverse cardiac events
      • metformin group 3.1% versus placebo group 1.1% (P = 0.16)
    • creatinine
      • metformin group 79 µmol/L (IQR 70 to 87 µmol/L) vs placebo group 79 µmol/L (IQR 72 to 89 µmol/L), (P =0 .61) 
    • glycated hemoglobin
      • metformin group 5.9% (IQR 5.6% to 6.1%) vs placebo group 5.9% (IQR 5.7% to 6.1%) (P=0.15)
  2. there were no
    • cases of lactic acidosis
    • deaths

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Meta Analysis

Munshi et al pooled data from 10 studies (4 randomized controlled trials, 6 observational studies, n=1248) comparing extracorporeal life support with mechanical ventilation in respiratory failure, and found:

  1. extracorporeal life support was associated with
    • no significant difference
      • in-hospital mortality
        • RR 1.02; 95% CI 0.79 to 1.33; I2 = 77%
    • restricted to veno-venous extracorporeal life support studies of randomized trials and quasi-randomized trials (3 studies; 504 patients)
      • reduced mortality
        • RR 0.64; 95% CI 0.51 to 0.79; I2 = 15%
    • increased bleeding
      • RR 11.44; 95% CI 3.11 to 42.06; I2 = 0%
    • In the H1N1 subgroup (3 studies, n=364)
      • lower hospital mortality
        • RR 0.62; 95% CI 0.45 to 0.8; I2 = 25%
  2. there were insufficient data to examine most secondary outcomes

Layek et al combined data from 10 randomized controlled trials (n=6,120) examining the efficacy of vasopressin in adult cardiac arrest patients, and found:

  1. vasopressin was associated with
    • no improvements in unselected populations for
      • return of spontaneous circulation (OR 1.19, 95% CI 0.93 to 1.52)
      • survival to hospital discharge (OR 1.13, 95% CI 0.89 to 1.43)
      • survival to hospital admission (OR 1.12, 95% CI 0.99 to 1.27)
      • favourable neurological outcome (OR 1.02, 95% CI 0.75 to 1.38)
    • improvements in “in-hospital” cardiac arrest patients
      • return of spontaneous circulation (OR 2.20, 95% CI 1.08 to 4.47] 
  2. when used as repeated boluses of 4-5 times titrating desired effects during CPR, subgroup analyses revealed equal or higher chance of
    • return of spontaneous circulation (OR 2.15, 95% CI 1.00 to 4.61)
    • higher possibility of survival to hospital discharge (OR 2.39, 95% CI 1.34 to 4.27)
    • favourable neurological outcome (OR 2.58, 95% CI 1.39 to 4.79)

Ruan and colleagues evaluated the effectiveness of corticosteroid therapy on the mortality of acute respiratory distress syndrome in 8 randomized controlled trials and 10 cohort studies (n=1,474), and found:

  1. in randomized controlled trials, corticosteroids had
    • a possible but statistically insignificant effect on ICU mortality
      • risk difference  -0.28; 95% CI -0.53 to -0.03 
      • relative risk 0.55; 95% CI 0.24 to 1.25
    • no effect on 60-day mortality
      • RD -0.01; 95% CI -0.12 to 0.10
      • RR 0.97; 95% CI 0.75 to 1.26
  2. in cohort studies
    • no effect on ICU mortality
      • RR 1.05; 95% CI 0.74 to 1.49
    • non-significantly increased 60-day mortality
      • RR 1.30; 95% CI 0.96 to 1.78
  3. in subgroup analysis by ARDS etiology
    • corticosteroids significantly increased mortality in influenza-related ARDS
      • 3 cohort studies, RR 2.45, 95% CI 1.40 to 4.27

Using data from from the European Medicines Agency and Roche, Jefferson et al reviewed clinical study reports for 83 randomised placebo controlled trials on adults and children who had confirmed or suspected exposure to natural influenza , including 23 trials in stage 1 (reliability and completeness screen) and 20 in stage 2 (formal analysis), evaluating the potential benefits and harms of oseltamivir, and found:

  1. In treatment trials
    • oseltamivir reduced
      • time to first alleviation of symptoms
        • in adults by 16.8 hours (95% CI 8.4 to 25.1 hours, P<0.001)
        • in healthy children by 29 hours (95% CI 12 to 47 hours, P=0.001)
    • no difference in
      • admissions to hospital in adults (risk difference 0.15%, 95% CI −0.91% to 0.78%, P=0.84)
      • risk of unverified bronchitis, otitis media, sinusitis, or any complication classified as serious or that led to study withdrawal
    • oseltamivir increased the risk of
      • in adults
        • nausea (risk difference 3.66%, 95% CI 0.90% to 7.39%; NNH 28, 95% CI 14 to 112)
        • vomiting (risk difference 4.56%, 95% CI 2.39% to 7.58%; NNH 22, 95% CI 14 to 42)
      • in children
        • vomiting (risk difference 5.34%, 95% CI 1.75% to 10.29%; NNH 19, 95% CI 10 to 57)
  2. In prophylaxis trials,
    • oseltamivir reduced symptomatic influenza in (based on 1 study)
      • participants by 55%
      • households
    • no significant effect on
      • asymptomatic influenza
      • reduction in transmission 
    • oseltamivir increased the risk of
      • psychiatric adverse events
      • headaches
      • renal events
      • nausea 


Observational Studies

Lonardo and colleagues performed a propensity matched analysis based on multi-center ICU database (2003-2009), comparing in a 1:1 ratio sedative infusions of propofol with either midazolam (2,250 matched patients) or lorazepam (1,054 matched patients) in critically ill mechanically ventilated patients, and found:

  1. propofol sedation was associated with
    • reduced hospital mortality
      • vs midazolam
        • risk ratio 0.76; 95% CI 0.69 to 0.82
      • vs lorazepam
        • risk ratio 0.78; 95% CI 0.68 to 0.89
    • for the 28-day ICU time period
      • increased ICU discharge (P<0.001)
        • propofol 78.9% vs midazolam 69.5%
        • propofol 79.2% vs lorazepam 71.9%
      • earlier removal from the ventilator (P<0.001)
        • propofol 84.4% vs midazolam 75.1%
        • propofol 79.2% vs midazolam 71.9%

Lilly investigated assessed the optimal method of managing increased risk for venous thrmboembolism based on 294,896 episodes of critical illness in 271 American adult intensive care units, and found:
  1. after adjustment for propensity to receive VTE prophylaxis, APACHE IV scores and management with mechanical ventilation, prophylactic anticoagulation was the only intervention associated with a lower risk of death compared with those not provided VTE prophylaxis
    • ICU mortality
      • hazard ratio 0.81, 95% CI 0.79 to 0.84, p<.0001
    • hospital mortality
      • hazard ratio 0.84, 95% CI 0.82 to 0.86, p<.0001
  2. mechanical devices, in comparison with no VTE prophylaxis, were not associated with a reduced mortality risk
  3. in a study of 87,107 pairs of patients matched for propensity to receive VTE prophylaxis
    • prophylactic anticoagulation was associated with a lower risk of death than those receiving only mechanical device prophylaxis
      • ICU sub-hazard ratio
        • 0.82, 95% CI 0.78 to 0.85; p < 0.001
      • hospital sub-hazard ratio
        • 0.82, 95% CI 0.79 to 0.85; p < 0.001

Jackson and colleagues followed up 821 critically ill patients with respiratory failure or shock in a prospective, multicentre cohort study, examining psychological and functional outcomes, and found:
  1. baseline data
    • median age of 61 years (IQR 51—71)
    • assessment post discharge
      • 448 patients at 3 months 
      • 382 patients at 12 months
  2. at least mild depression was present in
    • 37% at 3 months
    • 33% at 12 months
      • this depression was mainly due to somatic rather than cognitive—affective symptoms
  3. depressive symptoms were common among individuals without a history of depression
    • 30% at 3 months
    • 29% at 12 months
  4. post-traumatic distress disorder was present in
    • 7% at 3 and 12 months
  5. disabilities in
    • basic activities of daily living
      • 32% at 3 months
      • 27% at 12 months
    • instrumental activities of daily living
      • 26% at 3 months
      • 23% at 12 months

Malani et al provide an updated estimate of health care– and community-associated invasive methicillin-resistant Staphylococcus aureus infections in the USA in 2011, and found:
  1. 80,461 (95% CI  69,515 to 93,914) invasive MRSA infections 
    • which breakdown as:
      • health care–associated community-onset: 48,353 (95% CI 40,195 to 58,642)
      • hospital-onset infections: 14,156 (95% CI 10,096 to 20,440) 
      • community-associated infections: 16,560 (95% CI 12,806 to 21,811) 
  2. since 2005, adjusted national estimated incidence rates decreased by
    • health care–associated community-onset infections: 27.7% 
    • hospital-onset infections decreased: 54.2%;
    • community-associated infections decreased: 5.0%.
  3. among recently hospitalized community-onset (nondialysis) infections
    • 64% occurred 3 months or less after discharge
    • 32% of these were admitted from long-term care facilities

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Additional Studies

Randomized Controlled Trials

Meta Analyses

 Observational Studies

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Cochrane Reviews

New

Updated

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Guidelines and Position Statements

 

Case Reports

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Clinical Review Articles

Neurological

Circulatory    

Respiratory

Gastrointestinal

Renal

Haematological

Sepsis

Trauma

Burns

Toxicology

Miscellaneous

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Annual Update in Intensive Care and Emergency Medicine 2014

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Basic Science Review Articles

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Non-Clinical Review Articles

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I hope you find these brief summaries and links useful.


Until next week

Rob

 

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