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Newsletter 124 / April 20th 2014

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Welcome to the 124th 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 research studies include randomized controlled trials on necrotizing soft tissue infections, rasied intra-cranial pressure management in children, and uric acid for ischaemic stroke; meta analyses address rehabilitation for post-intensive care syndrome, statins for sepsis, and glutamine supplementation; observational studies focus on dysnatraemia in the critically ill, outcomes from septic shock in patients with cirrhosis, and a global audit of the burden of critical illness. Additional studies investigate azithromycin for the prevention of COPD exacerbations, therapeutic hypothermia for cardiac arrest, timing of initiation of renal replacement therapy, delirium screening and imaging in disorders of consciousness. 

There are two guideline, on tricyclic antidepressant toxicity and resistant TB. There is one study critique, looking at the DESTINY II trial, and two editorials on Brugada phenocopy and non-inferiority trials. There are several commentaries, with three on end-of-life care, including a discussion on paediatric euthanasia in Belgium. There are two case reports on an unusual ECG finding in the critically ill, the spiked helmet sign, and a first-in-human report of the use of engineered autologous cartilage tissue.

Amongst the clinical review articles are papers on traumatic brain injury, myocardial infarction, post cardiac arrest syndrome, ARDS, tertiary peritonitis, atypical haemolytic uraemic syndrome, sepsis-related DIC, resuscitative thoracotomy, trauma-related critical care, and ICU scoring systems. Non-clinical review articles discuss time management and grant application writing.

Over the last few days there has been much heated debate online on the utility of cricoid pressure, so this becomes the topic for This Week's Papers, starting with a recent general paper in tomorrow's Paper of the Day.

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Research

Randomized Controlled Trials

Bulger and colleagues completed a prospective, multi-centre, randomized, placebo-controlled, double-blinded study evaluating the safety of AB103, a peptide mimetic of the T-lymphocyte receptor CD28, in 43 patients (40 in modified intention-to-treat analysis), with necrotizing soft tissue infection. Patients were randomized into three groups; a single low intravenous dose (0.25 mg/kg, n=15), a single high IV dose (0.5 mg/kg, n=15) or placebo (n=10), administered with 6 hours of diagnosis of necrotizing soft tissue infection. The authors found:

  1. groups were similar at baseline
  2. AB103 treatment was associated with:
    • improvements in
      • SOFA score at day 14 (mean change) (p=0.04)
        • AB103 high-dose -2.8
        • AB103 low-dose -2
        • placebo +1.3
    • no significant difference in
      • number of debridements (mean/SD) (P=0.56)
        • AB103 high-dose 2.2 (1.1)
        • AB103 low-dose 2.3 [1.2]
        • placebo 2.8 [2.1] 
      • ICU–free days
      • ventilator-free days 
      • plasma and tissue cytokine levels
  3. there were no drug-related adverse events 

Abstract:  Bulger. A Novel Drug for Treatment of Necrotizing Soft-Tissue Infections. A Randomized Clinical Trial. JAMA Surg 2014;epublished April 16th


Kumar and colleagues performed a prospective, open-label randomized controlled trial, comparing cerebral perfusion pressure-targeted therapy (n=55) with intracranial pressure-targeted therapy (n=55) in 110 neurologically impaired critically ill children with raised intracranial pressure due to acute CNS infection. CPP was mainatined at ≥ 60 mm Hg, using normal saline and dopamine, with noradrenaline if needed; ICP was maintained < 20 mm Hg with osmotherapy while ensuring maintanence of normal blood pressure. The authors found:

  1. intracranial pressure-targeted therapy was associated with:
    • increased 90-day mortality 
      • 38.2% vs 18.2%; relative risk = 2.1; 95% CI 1.09 to 4.04; p = 0.020
  2. cerebral perfusion pressure-targeted therapy was associated with (median/IQR):
    • decreased
      • duration
        • PICU stay (13 d [10.8 to 15.2 d] vs 18 d [14.5 to 21.5 d], p = 0.002) 
        • mechanical ventilation (7.5 d [5.4 to 9.6 d] vs 11.5 d [9.5 to 13.5 d], p = 0.003)
      • prevalence of
        • hearing deficit (8.9% vs 37.1%; RR 0.69; 95% CI 0.53 to 0.90; p = 0.005)
        • neurodisability at
          • discharge from PICU (53.3% vs 82.9%; RR 0.37, 95% CI 0.17 to 0.81; p = 0.005) 
          • 90 days after discharge (37.8% vs 70.6%; RR 0.47, 95% CI 0.27 to 0.83; p = 0.004)
    • increased
      • modified Glasgow Coma Scale score at 72 hours (10 [8-11] vs 7 [4-9], p < 0.001)

Abstract:  Kumar. Randomized Controlled Trial Comparing Cerebral Perfusion Pressure-Targeted Therapy Versus Intracranial Pressure-Targeted Therapy for Raised Intracranial Pressure due to Acute CNS Infections in Children. Critical Care Med 2014;epublished April 1st


Chamorro and colleagues compared uric acid (1000mg infusion, n=211), which has potential antioxidant and neuroprotective effects, with placebo (n=200), in 411 adults with

  1. acute ischaemic stroke
  2. alteplase within 4·5 h of symptom onset
  3. National Institutes of Health Stroke Scale (NIHSS) score (>6 and ≤25)
  4. premorbid (assessed by anamnesis) modified Rankin Scale (mRS) score (≤2)

and found:

  1. uric acid was associated with:
    • a trend for excellent outcome (mRS score of 0—1, or 2 if premorbid score was 2) (1° outcome)
      • 39% vs 33%; adjusted risk ratio 1·23, 95% CI 0·96 to 1·56; p=0·099
    • no difference in
      • death
        • uric acid group 13% versus placebo 16%
      • symptomatic intracerebral haemorrhage
        • uric acid group 4% versus placebo 3%
      • gouty arthritis
        • uric acid group <1% versus placebo 2%
      • serious adverse events (as % of adverse events)
        • uric acid group 12% versus placebo 13%, p=0·703

Abstract:  Chamorro. Safety and efficacy of uric acid in patients with acute stroke (URICO-ICTUS): a randomised, double-blind phase 2b/3 trial. Lancet Neurology 2014;13(5):453-460

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Meta Analyses

Mehlhorn et al pooled data from 18 studies (n=2,510) evaluating rehabilitation interventions in post-ICU patients, and found:

  1. ICU diaries reduced
    • new-onset posttraumatic stress disorder at 3 months (5% vs 13%, p = 0.02)
    • mean Impact of Event Scale-Revised score after 12 months (21.0 vs 32.1, p = 0.03)
  2. ICU follow-up clinic reduced
    • Impact of Event Scale for women (20 vs 31; p < 0.01)
  3. a self-help manual was associated with
    • fewer patients scoring high in the Impact of Event Scale after 8 weeks (p = 0.026)
      • but not after 6 months

Abstract:  Mehlhorn. Rehabilitation Interventions for Postintensive Care Syndrome: A Systematic Review. Critical Care Med 2014;42(5):1263-1271


Wan et al reviewed data from 5 randomized controlled trials (n=867) and 27 observational studies (n=337,648), examining the effects of statins on mortality from infection and sepsis, and found:

  1. in randomized controlled trials
    • statins did not significantly decrease mortality
      • in-hospital 
        • RR 0.98; 95% CI 0.73 to 1.33
      • 28-day mortality
        • RR 0.93; 95% CI 0.46 to 1.89
  2. in observational studies,
    • statins were associated with a significant decrease in mortality 
      • adjusted data
        • RR 0.65; 95% CI 0.57 to 0.75
      • unadjusted data
        • RR 0.74; 95% CI 0.59 to 0.94

Full Text:  Wan. Effect of statin therapy on mortality from infection and sepsis: a meta-analysis of randomized and observational studies. Critical Care 2014;18:R71


Wischmeyer et al reviewed data from 26 randomized controlled trials (n=2,484) investigating parenteral glutamine in critically ill patients, and found:

  1. parenteral glutamine was associated with
    • a trend towards a reduction of mortality
      • relative risk 0.88, 95% CI 0.75 to 1.03, P = 0.10
    • a significant reduction in hospital mortality
      • RR 0.68, 95% CI 0.51 to 0.90, P = 0.008
    • a trend towards reductions in
      • infectious complications
        • RR 0.86, 95% CI 0.73 to 1.02, P =0.09
      • ICU length of stay 
        • weighted mean difference - 1.91, 95% CI -4.10 to 0.28, p = 0.09
    • a reduction in
      • hospital length of stay
        • weighted mean difference -2.56, 95% CI -4.71 to -0.42, P = 0.02

Full Text: Wischmeyer. Parenteral glutamine supplementation in critical illness: a systematic review. Critical Care 2014;18:R76

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Observational Studies

Darmon and colleagues investigated the effect of dysnatremia (serum Na <135 mmol/L or > 145 mmol/L) in 18 French ICUs from 2005 to 2012, and found:

  1. 7,067 patients were included, of which,
    • by day 1
      • hyponatraemia occurred in 25.9%
      • hypernatraemia occurred in 9.0% 
    • by day 3
      • correction had occurred in
        • hyponatremia: 55.7%
        • hypernatremia 62.0%
      • persistent dysnatraemia at day 3 was independently associated with higher day 28 mortality
        • hyponatremia: OR 1.31; 95% CI 1.06 to 1.61
        • hypernatraemia: OR 1.86; 95% CI 1.37 to 2.54
  2. 28 day mortality was not associated with
    • day 3 correction of dysnatraemia
    • ICU acquired hyponatraemia
  3. median correction rate from days 1 to 3 was 2.58 mmol/L per day (IQR 0.67 – 4.55)
  4. higher natremia correction rate was associated with lower
    • crude 28 day mortality 
      • OR per mmol/L per day 0.97; 95% CI 0.94 to 1.00; p=0.04
    • adjusted day 28 mortality rate
      • OR per mmol/L per day 0.93; 95% CI 0.90 to 0.97; P = 0.0003

Abstract:  Darmon. Influence of Early Dysnatremia Correction on Survival of Critically Ill Patients. Shock 2014;41(5):394–399


Galbois and colleagues performed a multicenter, retrospective cohort study from 1998 to 2010, of 31,251 patients with septic shock, including 2,383 (7.6%) patients with cirrhosis, and found:

  1. compared with noncirrhotic patients, patients with cirrhosis had
    • higher
      • simplified Acute Physiology Score II (63.1 +/- 22.7 vs 58.5 +/- 22.8, p < 0.0001)
      • prevalence of
        • renal dysfunction (71.5% vs 54.8%, p < 0.0001)
        • neurological dysfunction  (26.1% vs 19.5%, p < 0.0001)
      • mortality
        • ICU (70.1% vs 48.3%, p<0.0001; adjusted odds ratio 2.524, 95% CI 2.279 to 2.795)
        • hospital mortality (74.5% vs 51.7%, p<0.0001)
    • in patients with cirrhosis, factors independently associated with in-ICU mortality were:
      • medical admission, Simplified Acute Physiology Score II, mechanical ventilation, renal replacement therapy, spontaneous bacterial peritonitis, positive blood culture, fungal infection
    • over the study period
      • prevalence of septic shock in patients with cirrhosis increased from
        • 8.64 to 15.67 per 1,000 admissions to ICU (p < 0.0001) 
      • ICU mortality decreased from 73.8% to 65.5%  (p = 0.01)
        • despite increasing Simplified Acute Physiology Score II
      • ICU mortality decreased in those receiving
        • mechanical ventilation (84.7% to 68.5%, p = 0.004) 
        • renal replacement therapy (91.2% to 78.4%, (p = 0.04)

Abstract:  Galbois. Improved Prognosis of Septic Shock in Patients With Cirrhosis: A Multicenter Study. Crit Care Med 2014;epublished April 11th


Vincent et al performed an international (84 countries, 730 centres, 10,069 patients) 10 day audit assessing ICU mortality, and found:

  1. regional recruitment was
    • Europe (5445 patients; 54·1%)
    • Asia (1928; 19·2%)
    • the Americas (1723; 17·1%)
    • Oceania (439; 4·4%)
    • the Middle East (393; 3·9%)
    • Africa (141; 1·4%)
  2. 2973 patients (29·5%) had sepsis on admission or during the ICU stay
  3. mortality rates
    • ICU
      • overall 16·2% (95% CI 15·5 to 16·9) 
      • in sepsis 25·8% (95% CI 24·2 to 27·4) 
    • hospital
      • overall 22·4% (95% CI 21·6 to 23·2) 
      • in patients with sepsis 35·3% (95% CI 33·5 to 37·1) 
  4. using a multilevel analysis, the unconditional model suggested significant variation in the individual risk of in-hospital death
    • between-country (var=0·19, p=0·002)
    • between-hospital (var=0·43, p<0·0001) 
  5. a stepwise increase in the adjusted risk of in-hospital death according to decrease in global national income

Abstract:  Vincent. Assessment of the worldwide burden of critical illness: the Intensive Care Over Nations (ICON) audit. Lancet Respiratory Medicine 2014;epublished April 14th

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Additional Studies of Interest

Randomized Controlled Trials

Meta Analyses

Observational Studies

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Guidelines and Position Statements

 
 

Case Report

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Clinical Review Articles

Neurological

Circulatory

Respiratory

Gastrointestinal

Hepatobiliary

Renal

Endocrine

Haematological

Sepsis

Trauma

Miscellaneous

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