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Newsletter 125 / April 27th 2014

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Welcome to the 125th 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. It's a relatively quiet week on the research front, but an abundance of commentaries and review articles provide plenty of reading for the next week.

This week's research studies include randomized controlled trials on ulinastatin for severe sepsis, prehospital stroke management, paediatric status epilepticus and tuberculous meningitis; meta analyses address carbapenam-associated seizures, lung ultrasound for pneumonia and noninvasive ventilation for post-extubation respiratory failure; observational studies focus on glycopeptide use for Enterococcus faecalis bacteraemia, ventilator-associated pneumonia and ventilator-associated condition. Additional studies investigate nasotracheal intubation, surgical scrub wearing outside the theatre complex, ischaemic stroke and clinical trial registration.

This week's guidelines and position statements include a new definition of epilepsy, plus guidance on pressure ulcer management and antiplatelet therapy in CABG. There are four study critiques looking at the RAIN, HOPE ICU, CHEST, and TTM studies. Amongst the commentaries are papers on patient-ventilator asynchrony and the ICU of the future, as well as one case report on thoraco-abdominal impalement injury. Amongst the clinical review articles are papers on sedation interruption, perioperative myocardial ischaemia, short bowel syndrome, micronutrients, heparin-induced thrombocytopaenia, coronaviruses, patient safety and wilderness medicine.

If you prefer a break from all the serious reading, take a look at the general interest articles, containing the latest episode of Lemmingaid.

The topic for This Week's Papers is critical care iatrogenesis, starting with a paper on ventilator-induced lung injury in tomorrow's Paper of the Day.

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Research

Randomized Controlled Trials

Karnad and colleagues compared ulinastatin (200,000 IU 12 hourly for 5 days, n=55), a serine protease inhibitor, with placebo (n=59), in patients within 48 hours of onset of severe sepsis, and found:

baseline data
- mean APACHE II score: 13.4 (SD 4.4)
- 42% receiving mechanical ventilation
- 51% receiving vasopressors
- 35% had multiple organ failure
ulinastatin was associated with
- intention-to-treat analysis
  - no significant reduction in 28 day mortality
    - ulinastatin: 10.2 % (n=6) vs. placebo: 20.6 % (n=13) (p = 0.11)
- modified intention-to-treat analysis (patients receiving six or more doses of study drugs)
  - reduced 28 day mortality
    - ulinastatin: 7.3 % (n=4) vs. placebo: 20.3% (n=12) (p = 0.045)
    - odds ratio 0.26, 95 % CI 0.07 to 0.95; p = 0.042
- reduced
  - incidence of new-onset organ failure
    - 10 vs. 26 patients, p = 0.003)
  - hospital stay
    - 11.8 ± 7.1 days vs. 24.2 ± 7.2 days, p < 0.001
- increased
  - ventilator-free days
    - 19.4 ± 10.6 days vs. 10.2 ± 12.5 days, p = 0.019

Full Text: Karnad. Intravenous administration of ulinastatin (human urinary trypsin inhibitor) in severe sepsis: a multicenter randomized controlled study. Intensive Care Med 2014;epublished April 16th

Ebinger and colleagues compared weeks (3,213 patients) with the utility of a prehospital stroke unit, consisting of a Stroke Emergency Mobile (STEMO) ambulance containing a CT scanner, point-of-care laboratory, and telemedicine connection; a stroke identification algorithm at dispatcher level; and a prehospital stroke team, with weeks (2,969 patients) of conventional ambulance care in 6,182 patients with suspected stroke, and found:

groups were similar at baseline
1. age 74
2. 45% male
STEMO availability (n=3,213) was associated with
- reduced alarm-to-thrombolysis times
  - minus 15 minutes (95% CI 11 to 19)
  - 76.3 min (95% CI 73.2 to 79.3) vs 61.4 min (95% CI 58.7 to 64.0) p < 0.001
- increased thrombolysis rates in ischemic stroke
  - 29% versus 21%; difference 8%, 95% CI 4% to 12%; p < 0.001
STEMO deployment (n=1,804) was associated with
- reduced alarm-to-thrombolysis times
  - minus 25 minutes (95% CI 20 to 29; p < 0.001)
  - 76.3 min (95% CI 73.2 to 79.3) versus 51.8 min (95% CI 49.0 to 54.6)
- increased thrombolysis rates in ischemic stroke
  - 33% versus 21%; difference 12%, 95% CI 7% to 16%; p < 0.001
- no increase in
  - intracerebral hemorrhage
    - adjusted odds ratio with STEMO 0.42, 95% CI 0.18 to 1.03; p = 0.06
  - 7-day mortality
    - adjusted odds ratio with STEMO 0.76; 95% CI 0.31 to 1.82; p = 0.53

Abstract: Ebinger. Effect of the Use of Ambulance-Based Thrombolysis on Time to Thrombolysis in Acute Ischemic Stroke. A Randomized Clinical Trial (PHANTOM-S Trial). JAMA 2014;311(16):1622-1631

Chamberlain and colleagues compared diazepam (0.2 mg/kg, n=140) with lorazepam (0.1 mg/kg, n=133) in 273 children (aged 3 months to 18 years) with status epilepticus, repeating half the dose after 5 minutes if unsuccessful, followed by fosphenytoin at 12 minutes if ongoing status, and found:

no difference in
- cessation of status epilepticus for 10 minutes without recurrence within 30 minutes
  - diazepam group 72.1% versus lorazepam group 72.9%
  - absolute efficacy difference of 0.8% (95% CI −11.4% to 9.8%)
- requirement for assisted ventilation
  - diazepam group 16.0% vs lorazepam group 17.6%
  - absolute risk difference 1.6% (95% CI −9.9% to 6.8%)
- secondary outcomes
lorazepam patients were more likely to be sedated
- 66.9% vs 50%
- absolute risk difference 16.9% (95% CI 6.1% to 27.7%)

Abstract: Chamberlain. Lorazepam vs Diazepam for Pediatric Status Epilepticus. A Randomized Clinical Trial. JAMA 2014;311(16):1652-1660

Kalita and colleagues performed an open-label comparison of levofloxacin (10 mg/kg, maximum 500 mg) with rifampicin (10 mg/kg, maximum 450 mg) in 60 patients with tuberculous meningitis also treated with isoniazid, pyrazinamide, ethambutol, prednisolone and aspirin, and found:

at baseline
- median age 34.5 (16-75) years
- groups were similar with respect to
  - clinical findings
  - MRI imaging
levofloxacin therapy was associated with
- a trend for reduced 6 month mortality
  - 21.7% vs 38.3%; p = 0.07
- reduced 6 month mortality on Cox regression analysis
  - hazard ratio 2.13, 95% CI 1.04 to 4.34, p = 0.04
- no difference
  - in functional outcome (p = 0.47)
    - but in intention-to-treat analysis,
      - levofloxacin 21.3% (10/47) vs rifampicin 13.5% (5/37)
  - repeat MRI findings
- increased discontinuation due to serious adverse events
  - 16 vs 4; p=0.01

Abstract: Kalita. Safety and efficacy of levofloxacin versus rifampicin in tuberculous meningitis: an open-label randomized controlled trial. J Antimicrob Chemother 2014;epublished April 20th

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Meta Analyses

Cannon et al pooled data from all randomized controlled trials comparing carbapenems (imipenem, meropenem, ertapenem and doripenem) with each other and with non-carbapenem antibiotics to assess the risk of seizures, and found:

carbapenams were associated with
- increased seizure risk
  - 2 per 1000 persons (95% CI 0.001 to 0.004)
  - OR 1.87 (95% CI 1.35 to 2.59)
- largely attributed to imipenem
  - 4 patients per 1000 (95% CI 0.002 to 0.007)
  - OR 3.50 (95% CI 2.23 to 5.49)
none of the other carbapenems were associated with increased seizure
- odds ratios
  - meropenem: 1.04 (95% CI 0.61 to 1.77)
  - ertapenem: 1.32 (95% CI 0.22 to 7.74)
  - doripenem: 0.44 (95% CI 0.13 to 1.53)

Abstract: Cannon. The risk of seizures among the carbapenems: a meta-analysis. J Antimicrob Chemother 2014;epublished April 16th

Santosham et al reviewed data from 10 studies (n=1,172, 4 studies in the critically ill) comparing the diagnostic accuracy of lung ultrasound with chest radiography or CT scanning and/or clinical criteria for pneumonia, and found:

lung ultrasound was performed by
- highly-skilled sonographers (7 studies)
- trained physicians (2 studies)
- unmentioned (1 study)
lung untrasound duration
- maximum 13 minutes
probes used were
- 3.5-5 MHz micro-convex transducer (9 studies)
- 5-9 MHz convex probe (1 study)
lung ultrasound test characteristics
- sensitivity 94% (95% CI 92% to 96%)
- specificity 96% (95% CI 94% to 97%)
- positive liklihood ratio 16.8 (95% CI 7.7 to 37.0)
- negative liklihood ratio 0.07 (95% CI 0.05 to 0.10)
- area-under-the-ROC curve 0.99 (95% CI 0.98 to 0.99)

Full Text: Santosham. Lung ultrasound for the diagnosis of pneumonia in adults: a systematic review and meta-analysis. Respiratory Research 2014;15:50

Lin et al reviewed ten studies (n=1,382) comparing noninvasive ventilation with standard medical therapy in the management of postextubation respiratory failure, and found:

in patients with established postextubation respiratory failure (2 studies, n=302)
- NIV was not associated with reductions in
  - reintubation rate (RR 1.02, 95% CI 0.83 to 1.25)
  - ICU mortality (RR 1.14, 95% CI 0.43 to 3.00)
in patients with early NIV after extubation (n=1,080)
- NIV was not associated with reductions in
  - reintubation rate (RR 0.75, 95% CI 0.45 to 1.15)
in patients with planned NIV use (n=849)
- NIV use was associated with reductions in
  - reintubation rate (RR 0.65, 95% CI 0.46 to 0.93)
  - ICU mortality rate (RR 0.41, 95% CI 0.21 to 0.82)
  - hospital mortality rate (RR 0.59, 95% CI 0.38 to 0.93)

Abstract: Lin. The efficacy of noninvasive ventilation in managing postextubation respiratory failure: a meta-analysis. Heart Lung 2014;43(2):99-104

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Observational Studies

Foo and colleagues completed a retrospective cohort study comparing an appropriate β-lactam (n = 126) with a glycopeptide (n = 46) for the management of 172 episodes of Enterococcus faecalis bacteraemia, and found:

glycopeptide therapy was associated with
- increased 30 day mortality
  - 26.1% vs 11.1%, p = 0.015
independent predictors of 30 day mortality were
- glycopeptide use
  - OR 2.46, 95% CI 1.01 to 6.02; p = 0.048
- APACHE II score
  - OR 1.10, 95% CI 1.02 to 1.18; p = 0.011
- malignancy
  - OR 2.58, 95% CI 1.03 to 6.49; p = 0.044

Abstract: Foo. Glycopeptide use is associated with increased mortality in Enterococcus faecalis bacteraemia. J Antimicrob Chemother 2014;epublished April 16th

Lorente and colleagues completed a prospective observational study, comparing the incidence of ventilator-associated pneumonia in 284 critically ill patients being mechanically ventilated > 48 hours, receiving either continuous (n=150) or intermittent (n=134) control of endotracheal tube cuff pressure, and found:

a lower incidence of VAP was associated with
- continuous cuff pressure control
  - 22.0% vs 11.2%; p=0.02
  - OR 0.45; 95% CI 0.22 to 0.89; p=0.02
  - HR=0.45; 95% CI=0.24 to 0.84; p=0.01
- subglottic drainage endotracheal tube
  - OR 0.39; 95% CI 0.19 to 0.84; p=0.02
  - HR=0.29; 95% CI=0.15 to 0.56; p<0.001
no interaction between type of endotracheal cuff pressure control system (continuous or intermittent) and endotracheal tube (with or without subglottic drainage)
- OR 0.41; 95% CI 0.07 to 2.37; p=0.32
- HR 0.35; 95% CI 0.06 to 1.84; p=0.21

Full Text: Lorente. Continuous endotracheal tube cuff pressure control system protects against ventilator-associated pneumonia. Critical Care 2014;18:R77

Lewis and colleagues completed a retrospective case-control study, comparing 110 patients with ventilator-associated conditions with 110 matched controls without ventilator-associated conditions, and found:

groups were similar at baseline
risk factors for ventilator-associated conditions
- mandatory modes of ventilation
  - odds ratio 3.4; 95% CI 1.6 to 8.0
- positive fluid balance
  - odds ratio 1.2 per L positive; 95% CI 1.0 to 1.4
possible risk factors for infection-related ventilator-associated complications
- benzodiazepines prior to intubation
  - odds ratio 5.0; 95% CI 1.3 to 29
- total opioid exposures
  - odds ratio 3.3 per 100 μg fentanyl equivalent/kg; 95% CI 0.90 to 16
- paralytic medications
  - odds ratio 2.3; 95% CI 0.79 to 80
traditional ventilator bundle elements were not associated with ventilator-associated conditions or infection-related ventilator-associated complications
- semirecumbent positioning
- oral care with chlorhexidine
- venous thromboembolism prophylaxis
- stress ulcer prophylaxis
- daily spontaneous breathing trials
- sedative interruptions