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Newsletter 113 / February 2nd 2014

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Welcome to the 113th 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 over 300 clinical and scientific journals.

This week's research studies include randomized controlled trials on glycaemic control, NIV post lung resection, and β2 agonism for donor lung optimization; meta analyses address starches and red cell transfusion thresholds; while observational studies focus on non-palliative ventilatory support in cancer patients,  delayed ICU admission, anidulafungin pharmacokinetics during CRRT and MERS-CoV infection.

This week there are guidelines on brain death, hyponatraemia, tropical fever and cerebral swelling. There is a single study critique, reviewing the TracMan study. There are several editorials, including articles on extracorporeal therapies, acute kidney injury and futile ICU management. In addition to a series of commentaries from The Lancet Respiratory Medicine, there are articles focusing on clinical reasoning and cardiac thrombi.

Amongst the clinical review articles are papers on dexmedetomidine, posttraumatic stress disorder, type II myocardial infarction, pulmonary embolism, cricoid pressure, hepatorenal syndrome, contrast-induced nephropathy, glycopeptide antibiotic biosynthesis, traumatic haemorrhage, military critical care, anaphylaxis, amniotic fluid embolism, and critical care transfer. One basic science review article looks at confounder selection.

If you prefer a break from all the serious reading, take a look at the latest Lemmingaid contribution, from the Journal of the Intensive Care Society.

The topic for This Week's Papers is neurological monitoring, starting with a general paper on brain monitoring in tomorrow's Paper of the Day.

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News

Research

Randomized Controlled Trials

Kalfon and colleagues completed a multi-center, randomized controlled trial in 2,684 French ICU patients (results available for 2,646) expected to require treatment in the ICU for at least 3 days, comparing tight computerized glucose control (TGC, 4.4–6.1 mmol/L, n=1,335) with conventional glucose control (CGC, <10.0 mmol/L, n=1,311), and found:

  1. groups were similar at baseline
  2. primary outcome
    • no difference in all-cause mortality at 90 days
      • TGC group 32.3 % versus CGC group 34.1 %
      • odds ratio for death in the TGC 0.92; 95 % CI 0.78–1.78; p = 0.32
  3. secondary outcome
    • increased incidence of severe hypoglycaemia (<2.2 mmol/L) with tight glycaemic control
      • 13.2 % versus 6.2 %; p < 0.001

Lorut et al conducted a multi-centre study in 360 COPD patients undergoing lung resection surgery, comparing conventional postoperative treatment (n = 179) with conventional postoperative treatment plus prophylactic noninvasive ventilation applied intermittently for 6 hours per day for 48 hours following surgery (n = 181), and found:

  1. primary outcome
    • no difference in rate of acute respiratory events at 30 days
      • prophylactic NIV group 31.5% versus control group 30.7 %; p = 0.93
  2. secondary outcomes
    • no difference in
      • acute respiratory failure
        • prophylactic NIV group 18.8 % versus controls 24.5%; p = 0.20
      • re-intubation rates
        • prophylactic NIV group 5.5% versus control group 7.2%; p = 0.53
      • mortality
        • prophylactic NIV groups 2.2% versus control group 5%; p = 0.16
      • complications
        • infectious
        • non-infectious
        • durations of stay
        • ICU
        • hospital stays
Ware and colleagues undertook a randomized, blinded, placebo-controlled trial comparing aerosolized albuterol (5 mg 4 hourly, n=260) with saline placebo (n=246) during active donor management in 506 organ donors, and found:
  1. groups were similar at baseline
  2. primary outcome
    • no difference in change in oxygenation (arterial partial pressure of oxygen/fraction of inspired oxygen [PaO2/FiO2] from enrollment to organ procurement)
    • p = 0.54
  3. secondary outcomes
    • no difference in
      • donor lung utilization 
      • albuterol 29% vs. placebo 32%, p = 0.44
    • albuterol therapy was associated with an increased risk of study drug dose modification due to tachycardia
      • reduced (13% vs. 1%, p < 0.001)
      • stopped (8% vs. 0%, p < 0.001)

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Meta Analysis

Wiedermann et al pooled data from 48 studies [37 human (n=635, 282 surgical patients; 45.9%) and 11 animal] evaluating clinical and preclinical data on hydroxyethyl starch (HES) tissue storage, and found:
  1. HES organ deposition was common
    • skin - 17 studies
    • kidney - 12 studies (highest tissued concentration)
    • liver - 8 studies
    • bone marrow - 5 studies
    • plus  lymph nodes, spleen, lung, pancreas, intestine, muscle, trophoblast, and placental stroma.
  2. HES tissue deposition
    • uptake into intracellular vacuoles occurred within 30 minutes
    • was cumulative, increasing with dose
    • occurred at the lowest cumulative doses (0.4 g kg−1) in 15%
    • could be extremely long-lasting,
      • persisting for
        • 8 years in skin
        • 10 years in kidney
    • was associated with
      • pruritus  in 17 studies
      • renal dysfunction in ten studies
      • was generally similar in animals and humans
Salpeter and colleagues reviewed data from 3 randomized trials (n=2,364) comparing a restrictive hemoglobin transfusion trigger of <7 g/dL, with a more liberal trigger, and found:
  1. a restrictive hemoglobin transfusion trigger of <7 g/dL was associated with reduced
    • in-hospital mortality (risk ratio 0.74; 95% CI 0.60-0.92)
    • total mortality (RR 0.80; 95% CI 0.65-0.98)
      • number needed to treat to prevent a death was 33
    • rebleeding (RR 0.64; 95% CI 0.45-0.90)
    • acute coronary syndrome (RR 0.44; 95% CI 0.22-0.89)
    • pulmonary oedema (RR 0.48; 95% CI 0.33-0.72)
    • bacterial infections (RR 0.86; 95% CI 0.73-1.00)
  2. less restrictive transfusion strategies were not superior to liberal transfusion strategies

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Observational Studies

Azevedo and colleagues performed a secondary analysis of a Brazilian multi-centre, prospective cohort study assessing clinical characteristics and outcomes of 263 cancer patients requiring non-palliative ventilatory support, and found:

  1. cancer characteristics
    • solid tumors, n=227
    • hematological malignancies, n=36
  2. initial use of mechanical ventilation was
    • NIV: 32%
      • 53% of this cohort subsequently required invasive ventilation
    • invasive mechanical ventilation: 68%
  3. hospital mortality rates were significantly different  (p<0.001)
    • all patients: 67%
    • NIV only: 40%
    • NIV was followed by IMV: 69%
    • IMV only: 73% 
  4. Adjusting for the type of admission, hospital mortality was associated with
    • newly diagnosed malignancy (OR 3.59; 95% CI 1.28-10.10)
    • recurrent or progressive malignancy (OR 3.67; 95% CI 1.25-10.81)
    • tumoral airway involvement (OR 4.04; 95% CI 1.30-12.56)
    • performance status (PS) 2-4 (OR 2.39; 95% CI 1.24-4.59)
    • NIV followed by MV (OR 3.00; 95% CI 1.09-8.18)
    • MV as initial ventilatory strategy (OR 3.53; 95% CI 1.45-8.60)
    • SOFA score (each point, excluding respiratory domain) (OR 1.15, 95% CI 1.03-1.29)

Yu et al performed a retrospective single centre study evaluating if a delay in ICU admission, waiting in a post anesthesia care unit and managed by anesthetists, affected ICU outcome for 2,279 critically ill surgical patients, and found:

  1. ICU admission characteristics
    • immediate admission - 91.9%
    • delayed ICU admission - 8.1%
  2. delayed admission was associated with
    • increased ICU mortality (p < 0.001)
    • prolonged waiting hours in PACU (≥6 hours) was associated with higher ICU mortality
      • adjusted odds ratio 5.32; 95% CI 1.25 to 22.60, p = 0.024
  3. longer PACU waiting times were not associated with
    • mechanical ventilation days
    • ICU length of stay
    • ICU cost
Aguilar and colleagues reviewed anidulafungin pharmacokinetic data (200mg day 1, 100mg days 2 & 3) from 12 critically ill patients receiving continuous venovenous haemodiafiltration for acute renal failure, and found:
  1. on day 3, peak plasma concentrations were
    • arterial: 6.2 ± 1.7 mg/L
    • venous: 7.1 ± 1.9 mg/L
  2. mean pre-filter trough concentration was 3.0 ± 0.6 mg/L
  3. mean AUC0–24 plasma anidulafungin levels
    • arterial: 93.9 ± 19.4 mg·h/L 
    • venous: 104.1 ± 20.3 mg·h/L
  4. regarding CRRT effects
    • there was no adsorption to synthetic surfaces
    • anidulafungin concentration in the ultradiafiltrate was below the limit of detection

Khaldi and colleagues reported data on 12 patients with confirmed or probable MERS-CoV infection from 3 Saudi Arabian ICUs, and found:

  1. 114 patients were tested for suspected MERS-CoV
    • 11 ICU patients (10%) met the definition of confirmed or probable cases
    • three of these patients were part of a healthcare-associated cluster that also included 3 healthcare workers
    • 1 infected healthcare worker became critically ill
  2. All 12 patients
    • had underlying comorbid conditions 
    • presented with acute severe hypoxemic respiratory failure
    • median APACHE II score was 28 (range 16-36)
  3. 92% had
    • extrapulmonary manifestations including
      • shock
      • acute kidney injury
      • thrombocytopenia
  4. 90 day mortality was 58%
  5. 1% of healthcare workers were infected (4/520)

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Other Studies of Interest

Randomized Controlled Trials

Observational Studies

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Guidelines

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Study Critique

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Editorial

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Commentaries

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Clinical Review

Neurological

Circulatory

Renal

Sepsis

Trauma

Immunology

Transfer

Miscellaneous

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