Newsletter 110 / January 12th 2014




Welcome to the 110th 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. It's the second newsletter in just four days, so it's smaller than usual.

This week's research studies include randomized controlled trials on renal replacement therapy modality, glycaemic control in paediatric critical care and antimicrobial plasma level monitoring; meta analyses address fluid type in ARDS, arterial catheters as a source of bloodstream infection, high volume haemofiltration for septic AKI and glutamine supplementation; while observational studies focus on sepsis outcomes and heparin-induced thrombocytopaenia.

This week's guidelines look at hospital-acquired infection prevention and the choosing wisely campaign. There is a single study critique reviewing the INTERACT 2 trial. Editorials reflect on declined trial enrollment, antidotes, ECMO and big data, while one commentary highlights ICU provision.

Amongst the clinical review articles are papers on myocarditis, ARDS, acute liver failure, renal transplantation rejection, sepsis pathophysiology, plus reviews on critical care over the past year as well as a series from The Lancet on research wastage.

The beginning of each month marks the addition of recently made open access articles from the major critical care journals, with 24 papers included.

The topic for This Week's Papers is a selection of guidelines from 2013, starting with a paper on red cell transfusion in the critically ill, from the British Committee for Standards in Haematology, in tomorrow's Paper of the Day.

Top 2013 Critical Care Research Review Podcast

This week I recorded a podcast with Chris Nickson from Life in the Fastlane and the SMACCgold Conference reviewing the main research findings of the past 12 months. The audio can be accesses via either the Life in the Fastlane or Intensive Care Network websites. I'll be joining Chris on the Gold Coast in Queensland, Australia, for this exciting conference in March.

Critical Care Reviews Meeting

After podcasting about the previous year's major research, next week we discuss them in person at the 2014 Critical Care Reviews Meeting. Nine months of preparations are complete and the final count down has begun. This promises to be one the best educational days of the year, so if you're within travelling distance, be sure to be in Belfast on Friday January 24th to hear the major research of 2013 discussed by Northern Ireland's top intensivists, speciality talks in haematolgy, microbiology and hepatology, as well as thought provoking presentations from our international guest speakers, Prof Alistair Nichol (Dublin/Melbourne), Prof Mervyn Singer (London) and Prof John Marshall (Toronto). The evening session provides an opportunity to chat with our guest speakers in a novel, informal setting - beside a blazing log fire in a beautiful lounge - perfect for a cold winters night. This will be followed by dinner, an after dinner talk by Prof Marshall, and the chance to meet new colleagues and friends. If you can't make it, a live twitter stream will be on #CCRMeeting, with all talks going online just a few days after the event.

This year, the meeting will be run in association with the Northern Ireland Intensive Care Society. Further details, the meeting programme, and registration can be accessed via these links.

Society of Critical Care Medicine 43rd Congress Vodcasts

SCCM have made available some of the presentations from their conference in San Francisco.

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Randomized Controlled Trials

Schefold and colleagues completed a single-center, prospective, randomized controlled trial in 252 critically ill patients comparing intermittent hemodialysis with continuous veno-venous hemofiltration, and found:

  1. groups were similar at baseline
  2. no difference in
    • 1° outcome
      • survival at 14 days after the end of RRT
        • IHD: 39.5% versus CVVH: 43.9%
        • odds ratio 0.84, 95% CI 0.49 to 1.41; P = 0.50
    • 2° outcomes
      • mortality
        • 14-day (P >0.5)
        • 30-day (P >0.5)
        • all-cause intra-hospital mortality (P >0.5)
      • days on
        • RRT
        • vasopressors
        • mechanical ventilation
      • length of stay
        • ICU
        • Intra-hospital

Full Text:  Schefold. The effect of continuous versus intermittent renal replacement therapy on the outcome of critically ill patients with acute renal failure (CONVINT): a prospective randomized controlled trial. Crit Care 2014;18(1):R11

Macrae et al performed a multicentre, parallel group, randomized controlled trial, comparing 1369 critically ill children, expected to require mechanical ventilation and vasoactive drugs for at least 12 hours, to either tight glycemic control (target blood glucose 72 to 126 mg/dL / 4.0 to 7.0 mmol/l, n=694), or conventional glycemic control (target level below 216 mg/dL /12.0 mmol/dL, n=675), and found:

  1. 60% had undergone cardiac surgery
  2. no difference in
    • 1° outcome
      • number of days alive and free from mechanical ventilation at 30 days
        • mean between-group difference 0.36 days (95% CI −0.42 to 1.14)
      • no subgroup difference
  • tight-glycaemic control was associated with increased incidences of
    • 2° outcomes
      • increased incidence of severe hypoglycaemia (blood glucose <36 mg/dl / 2.0 mmol/l)
        • 7.3% vs. 1.5%, P<0.001
      • lower mean 12-month costs
        • overall
        • in those undergoing non-cardiac surgery
          • mean cost difference −$13,120 (95% CI −$24,682 to −$1,559)

Abstract:  Macrae. A Randomized Trial of Hyperglycemic Control in Pediatric Intensive Care. N Engl J Med 2014; 370:107-118

 De Waele et al undertook a prospective, partially blinded, randomised controlled trial in 41 patients with normal kidney function treated with either meropenem or piperacillin/tazobactam, comparing dose adaption based on plasma levels versus conventional therapy. The predefined pharmacokinetic/pharmacodynamic target was 100% of time during a dosing interval that the free (f) drug concentration exceeded 4 times the minimum inhibitory concentration (MIC) (100 % fT>4MIC ). The authors found:

  1. pneumonia was the primary infectious diagnosis
  2. at baseline, 100 % fT>4MIC was achieved in
    • pip/taz patients: 21 %
    • meropenam patients: 0%
  3. Subsequently, 100 % fT>MIC was achieved in
    • pip/taz patients: 71 %
    • meropenam patients: 46 %
  4. The intervention was associated with
    • 76% of patients requiring dose adaptation
    • 5 patients requiring an additional increase
  5. At 72 h, the intervention was associated with improved target attainment rates for
    • 100 % fT>4MIC :  
      • 58% vs. 16%, p = 0.007
    • 100 % fT>MIC :
      • 95% vs. 68%, p = 0.045

Meta Analysis

Uhlig et al pooled data from three randomized controlled trials (n=206) in which patients with ARDS received either albumin or saline and found:

  1. overall risk of bias was unclear to high 
  2. no difference in
    • risk of death 
      • albumin 34.0% vs. saline 38.5%
      • relative risk 0.89, 95% CI 0.62 to 1.28, P = 0.539
  3. albumin was associated with
    • improved oxygenation (PaO2/FiO2)
      • at 48 hours
        • weighted mean difference improved 62 mmHg
        • 95% CI 47 to 77, P <0.001, I2 = 0%
      • at 7 days
        • weighted mean difference 20 mmHg
        • 95% CI 4 to 36, P = 0.017, I2 = 0%

O'Horo reviewed data from 49 studies, totalling 30,841 arterial catheters, examining the prevalence of arterial catheter-related bloodstream infection, and found:
  1. 222 cases of arterial catheter-related bloodstream infection
  2. incidence of
    • 3.40/1,000 catheters
    • 0.96/1,000 catheter days
  3. studies that cultured all catheters had a higher prevalence of arterial catheter-related bloodstream infection compared with arterial catheters cultured when suspected as the source for bloodstream infection
    • 1.26/1,000 vs. 0.70/1,000 catheter days
  4. femoral arterial catheters, in comparison with radial arterial catheters, were associated with an increased rate of arterial catheter-related bloodstream infection
    • relative risk 1.93; 95% CI 1.32 to 2.84; p = 0.001

Clark assessed data from four randomized controlled trials (n=470) comparing high-volume hemofiltration (HVHF, effluent rate >50 ml/kg per hour) with standard-volume hemofiltration (SVHF) for septic AKI, and found:

  1. no difference between HVHF and SVHF in
    • 1° outcome
      • 28-day mortality
        • odds ratio 0.76; 95% CI 0.45 to 1.29
    • 2° outcome
      • recovery of kidney function
      • lengths of stay
        • ICU
        • hospital 
      • vasopressor dose reduction
  2. HVHF was associated with increased adverse events
    • hypophosphatemia 
    • hypokalemia

Chen and colleagues evaluated randomized controlled trials, including REDOXS, utilizing glutamine-supplemented nutrition in critically ill patients, and found:
  1. glutamine supplementation, versus control, was associated with
    • no improvement in
      • mortality (17 RCTs, n=3,383)
        • in-hospital
        • at 6 months
        • worsened mortality in the high dose subgroup (>0.5 g/kg/day)
          • 33.5% vs. 28.2%; relative risk 1.18; 95% CI 1.02 to 1.38; P = 0.03
      • hospital length of stay (14 RCTs, n=2,777)
        • P = 0.24
    • reduced incidence of
      • nosocomial infections (15 RCTs, n=2,862)
        • RR 0.85; 95% CI 0.74 to 0.97; P = 0.02
          • surgical subgroup
            • RR 0.70; 95% CI 0.52 to 0.94; P = 0.04
          • parenteral subgroup
            • RR 0.83; 95% CI 0.70 to 0.98; P = 0.03

Observational Studies

Walkey and colleagues used data from 124 US academic hospitals evaluating associations between hospital severe sepsis caseload (n=56,997) and outcomes, and found:

  1. basic data
    • hospitals admitted 460±216 patients with severe sepsis
    • median length of stay 12.5 days (IQR 11.1 to 14.2)
    • median direct costs $26,304 (IQR $21,900 to 32,090)
    • average hospital mortality 25.6±5.3%
  2. higher severe sepsis case volume was associated with lower
    • unadjusted severe sepsis mortality (R2 =0.10, p=0.01) 
    • risk-adjusted severe sepsis mortality (R2=0.21, p<0.001)
  3. hospitals in the highest severe sepsis case volume quartile had an adjusted lower hospital mortality than hospitals in the lowest quartile
    • absolute difference 7% (95% CI 2.4-11.6%)
  4. there were no associations between case volume and resource utilization

Abstract:  Walkey. Hospital Case Volume and Outcomes among Patients Hospitalized with Severe Sepsis. Am J Respir Crit Care Med 2014;epublished January 8th

Matsumura et al evaluated the 4Ts scoring system against the antiplatelet factor 4/heparin complex antibodies (PF4/heparin Ab) test, in 104 critically ill patients with suspected heparin-induced thrombocytopenia, and found:

  1. no significant difference in the 4Ts scores between the PF4/heparin Ab positive and negative groups
  2. a positive predictive value (HIT patients/4T high score patients) of 15.4% (2/13),
  3. a negative predictive value (non-HIT patients/4T low score patients) of 87.5% (42/48),
  4. a false-negative rate for the 4Ts score (4T low score patients/HIT patients) of 54.5% (6/11)
  5. PF4/heparin Ab positive patients had longer stay in intensive care compared to the PF4/heparin Ab negative patients (P = 0.035)

Abstract:  Matsumura. Relationship between the 4Ts scoring system and the antiplatelet factor 4/heparin antibodies test in critically ill patients. Acute Medicine & Surgery 2014;1:36–43 

Other Studies of Interest

Meta Analyses

Observational Trials

Full Text:  Masson. Presepsin (soluble CD14 subtype) and procalcitonin levels for mortality prediction in sepsis: data from the Albumin Italian Outcome Sepsis trial. Critical Care 2014;18:R6

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Study Critiques

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Clinical Review Articles




Lancet Series on Research Waste

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Recently Made Open Access Articles

American Journal of Respiratory and Critical Care Medicine




Critical Care





Anesthesia & Analgesia



British Journal of Anaesthesia



Anaesthesia & Intensive Care


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I hope you find these brief summaries and links useful.

Until next week