Newsletter 106 / December 15th 2013




Welcome to the 106th 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.

Unusually, in this week's research, there are no randomized controlled trials, with attention focusing on a single interventional study, plus a plethora of meta analyses and observational studies. Meta analyses include investigations into stress ulcer prophylaxis, procalcitonin-guided therapy and clostridium difficile, with observational studies evaluating excessive surgical fluid balance, septic acute kidney injury, and lung ultrasound. There is a single festive study, examining the survival of chocolates in UK hospitals.

This week's guidelines look at antibiotic therapy in neutropaenia, IV fluids and AKI biomarkers. Editorials address the right ventricle, social media and Nelson Mandela, while commentaries focus on emergency surgery, resident hours, trial recruitment and respiratory updates. In addition to the usual tens of clinical review articles, this week there are fantastic supplements from the British Journal of Anaesthesia, British Journal of Surgery, BMJ Quality & Safety and the American Society of Hematology via their annual Education Book published with Hematology. A single non-clinical review article discusses selection for medical school in Switzerland. Correspondence is not usually featured, but the ongoing debate on the 6S study continues in the Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, with a reply from Chappell and colleagues again questioning the interpretation of the study results by the trial investigators.

The topic for This Week's Papers is hypersensitivity reactions, starting with a paper on perioperative anaphylaxis in tomorrow's Paper of the Day.


Critical Care Reviews Meeting

It's just 6 weeks to the 2014 Critical Care Reviews Meeting. This year we discuss the major studies from the past 12 months, hear from our international guest speakers, Prof Alistair Nichol (Dublin/Melbourne), Prof Mervyn Singer (London) and Prof John Marshall (Toronto), and have updates on ICU infections, massive haemorrhage and acute liver failure. 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 and the chance to meet new colleagues and friends.

If you're a drive or short flight away, it would be great to have you come along. Travel on Thursday, attend the meeting on Friday and see some of the local landmarks over the weekend, before returning home on Sunday evening after a great winter break. On Saturday visit the North Coast: the World Heritage site Giants Causeway, Carrick-a-Rede rope bridge, Dunluce Castle and Bushmills Distillary, the oldest distillary in the world; while on Sunday experience Belfast: the new acclaimed Titanic Centre followed by a famous black taxi tour describing the troubled past of one of Europe's now most vibrant cities. The Galgorm Resort and Spa is one of Northern Ireland's premier hotels and is a 30 minute drive from Belfast International Airport. Special room rates are available, by quoting the meeting. Please feel free to contact me if you're thinking about making the trip - it would be great to hear from you. Now is a good time to register before such thoughts are rightly forgotten during the approaching festivities.

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.

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Interventional Trials

Bergen and colleagues performed a single arm prospective interventional study, evaluating the effects of an oral health protocol (dental examination and education, plus pre-operative twice daily mouthwashes with chlorhexidine 0.12%) on the incidence of postoperative pneumonia in 226 patients having coronary artery bypass grafting (54%) or valve surgery (46%), and found:

  1. no between group differences in postoperative pneumonias (8%, n=9 each group)
    • dentate patients n=10
    • edentulous patients n=8
  2. postoperative pneumonia was significantly
    • increased with preoperative
      • tongue plaque (OR 17, P < 0.001) 
      • poor hygiene of the total superior dentures (OR 25, P < 0.001)
    • decreased with use of chlorhexidine
      • preoperatively (OR 0.06, P < 0.001)
      • on the day of surgery (OR 0.002, P < 0.001)
  3. postoperative pneumonia was associated with an increased risk of death
    • 4.32 % (9/208) vs. 33.3 % (6/19)
  4. mean pneumonia rate in ICU
    • 6 months before the study protocol:  32 per 1,000 ventilator-days
    • 6-month intervention period: 24 per 1,000 ventilator-days
    • next 6 months following the study: 10 per 1,000 ventilator-days

Abstract:  Bergan. Impact of improvement in preoperative oral health on nosocomial pneumonia in a group of cardiac surgery patients: a single arm prospective intervention study. Intensive Care Med 2013;40(1):23-31

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Meta Analysis

Krag and colleagues pooled data from 20 trials (n=1,971), comparing the effects of stress ulcer prophylaxis with either placebo or no prophylaxis in adult critically ill patients in the intensive care unit, and found:

  1. all studies had a high risk of bias
  2. stress ulcer prophylaxis was associated with
    • no improvements in
      • mortality (fixed effect model: RR 1.00, 95 % CI 0.84 to 1.20; P = 0.87; I2 = 0 %) 
      • hospital-acquired pneumonia (random effects: RR 1.23, 95 % CI 0.86 to 1.78; P = 0.28; I2 = 19 %)
    • improvement in
      • GI bleeding  (random effects: RR 0.44, 95 % CI 0.28 to 0.68; P = 0.01; I2 = 48 %)
        • but not using
          • trial sequential analysis (adjusted 95 % CI 0.18 to 1.11)
          • subgroup analysis

Abstract:  Krag. Stress ulcer prophylaxis versus placebo or no prophylaxis in critically ill patients : A systematic review of randomised clinical trials with meta-analysis and trial sequential analysis. Intensive Care Med 2013;40(1):11-22


Prkno and colleagues evaluated seven randomized controlled clinical trials or cohort studies (n=1,075) which compared procalcitonin-guided therapy with standard care in critically ill septic patients, and found:

  1. no difference between procalcitonin-guided therapy and standard treatment groups
    • hospital mortality (RR 0.91, 95% CI  0.61; 1.36)
    • 28-day mortality (RR 1.02, 95% CI 0.85; 1.23)
    • combined estimates of the length of stay in ICU and in hospital
  2. duration of antimicrobial therapy was significantly reduced with procalcitonin-guided therapy (HR 1.27, 95% CI 1.01 to 1.53)

Full Text:  Prkno. Procalcitonin-guided therapy in intensive care unit patients with severe sepsis and septic shock - a systematic review and meta-analysis. Critical Care 2013;17:R291


Slimings et al analysed data from 13 case–control and 1 cohort study (n=15 ,938) examing the association between antibiotic classes and hospital-acquired Clostridium difficile infection, and found:
  1. the strongest associations were found for
    • third-generation cephalosporins (OR   3.20, 95% CI = 1.80 to 5.71; n = 6 studies; I2 = 79.2%)
    • clindamycin (OR 2.86, 2.04 to 4.02; n = 6; I2 = 28.5%)
    • second-generation cephalosporins (OR 2.23, 1.47 to 3.37; n = 6; I2 = 48.4%)
    • fourth-generation cephalosporins (OR 2.14, 1.30 to 3.52; n = 2; I2 = 0.0%)
    • carbapenems (OR 1.84, 1.26 to 2.68; n = 6; I2 = 0.0%)
    • trimethoprim/sulphonamides (OR 1.78, 1.04 to 3.05; n = 5; I2 = 70%)
    • fluoroquinolones (OR 1.66, 1.17 to 2.35; n = 10; I2 = 64%) 
    • penicillin combinations (OR 1.45, 1.05 to 2.02; n = 6; I2  = 54%)
  2. sources of heterogeneity were
    • study population
    • timing of measurement of antibiotic exposure

Abstract:  Slimings. Antibiotics and hospital-acquired Clostridium difficile infection: update of systematic review and meta-analysis. J Antimicrob Chemother 2013;epublished December 8th

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Observational Studies

Silva and colleagues completed a multicentre, prospective cohort study evaluating the efect of intra-operative fluid balance in 479 patients undergoing major surgery who required postoperative ICU, and found:

  1. basic data
    • mean age 61.2 ± 17.0 years
    • median duration of surgery 4.0 (IQR 3.2 to 5.5) hours
    • intra-hospital mortality 8.8%
  2. non-survivors had a higher
    • intra-operative fluid balance
      • 1950 (1400 to 3400) mL vs. 1400 (1000 to 1600) mL, P <0.001
    • SAPS 3 score
      • 53.8 ± 12.3 vs. 40.6 ± 14.2; P <0.001
    • requirement for vasopressors intra-operatively
      • 78.4%  vs. 54.5%;  P=0.005
    • transfusion requirement
      • 43.2%  vs. 23.1%  P=0.007
  3. patients with a fluid balance >2000 mL intraoperatively had
    • longer ICU stay 4.0 (3.0 to 8.0) vs. 3.0 (2.0 to 6.0) days; P <0.001
    • higher incidence of complications,
      • infectious (41.9% vs. 25.9%, P = 0.001)
      • neurological (46.2% vs. 13.2%, P <0.001)
      • cardiovascular (63.2% vs. 39.6%, P <0.001)
      • respiratory complications (34.3% vs. 11.6%, P <0.001)
  4. In multivariate analysis, fluid balance was an independent risk factor for death
    • OR per 100 mL 1.024, 95% CI 1.007 to 1.041;  P = 0.006

Full Text:  Silva. The effect of excess fluid balance on the mortality rate of surgical patients: a multicenter prospective study. Critical Care 2013;17:R288


Poukkanen and colleagues completed a secondary analysis of the prospective, observational FINNAKI study, examing the association between mean arterial blood pressure and progression of septic acute kidney injury in 423 patients, based on 53,724 10-minute medians of MAP, and found:

  1. 36.2% (n=153) had progression of AKI
  2. patients with progression of AKI had significantly lower time-adjusted MAP than those without progression
    • 74.4 mmHg (68.3-80.8) vs. 78.6 mmHg (72.9-85.4); P < 0.001
      • a cut-off value of 73 mmHg for time-adjusted MAP best predicted AKI progression
  3. independent predictors of AKI progression were
    • chronic kidney disease
    • higher lactate
    • higher dose of furosemide
    • use of dobutamine 
    • time-adjusted MAP below 73 mmHg

Full Text:  Poukkanen. Hemodynamic variables and progression of acute kidney injury in critically ill patients with severe sepsis: data from the prospective observational FINNAKI study
Critical Care 2013;17:R295 


Xirouchaki et al performed a prospective, observational study examining the effect of lung ultrasound (253 examinations) on clinical decision making in 189 mechanically ventilated, critically ill patients, and found:

  1. reasons for undertaking sonographic examinations were
    • unexplained deterioration of arterial blood gases  (42.7 %, n=108 studies) 
    • suspected pathologic entity (57.3 %, n=145 studies)
      • pneumothorax (n=60)
      • significant pleural effusion (n=34)
      • diffuse interstitial syndrome (n=22)
      • unilateral lobar or total lung atelectasis (n=15)
      • pneumonia (n=14)
  2. lung ultrasound significantly influenced the decision-making process (net reclassification index 85.6 %)
  3. management was changed directly as a result of the examination in 47 % (119/253)
    • invasive interventions occurred in 81 cases (chest tube, bronchoscopy, diagnostic thoracentesis/fluid drainage, continuous venous–venous hemofiltration, abdominal decompression, tracheotomy)
    • non-invasive interventions in in 38 cases (PEEP change/titration, recruitment maneuver, diuretics, physiotherapy, change in bed position, antibiotics initiation/change)
    • unexpected finding occurred in 21% (53/253 cases)
      • pneumothorax (n=7)
      • significant pleural effusion (n=9)
      • pneumonia (n=9)
      • unilateral atelectasis (n=16)
      • diffuse interstitial syndrome (n=12)

Abstract:  Xirouchaki. Impact of lung ultrasound on clinical decision making in critically ill patients. Intensive Care Med 2013;40(1):57-65

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Other Studies of Interest

Meta Analyses

Observational Studies


Studies of Absolutely No Interest

Gajendragadkar and colleagues undertook a multicentre, prospective, covert observational study, examing the survival times of chocolates (n=258), both Quality Street (Nestlé) and Roses (Cadbury), on four UK wards, and found:

  1. 191 out of 258 (74%) chocolates were observed being eaten
  2. mean total observation period was 254 minutes (95% CI 179 to 329)
  3. median survival time of a chocolate was 51 minutes (39 to 63)
  4. chocolate consumption was non-linear, with an initial rapid rate of consumption that slowed with time
    • an exponential decay model best fitted these findings (model R2=0.844, P<0.001)
  5. survival half life (time taken for 50% of the chocolates to be eaten) was 99 minutes.
  6. mean time taken to open a box of chocolates from first appearance on the ward was 12 minutes (95% CI 0 to 24)
  7. Quality Street chocolates survived longer than Roses chocolates (hazard ratio for survival of Roses vs. Quality Street 0.70, 95% CI 0.53 to 0.93; P=0.014)
  8. percentages of chocolates consumed were by
    • healthcare assistants (28%) 
    • nurses (28%)
    • doctors (15%)

Full Text:  Gajendragadkar. The survival time of chocolates on hospital wards: covert observational study. BMJ 2013;347:f7198

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Clinical Review Articles









From the American Society of Hematology Annual Education Book

Trauma-Induced Coagulopathy: A Clinical and Scientific Perspective

Transfusion Medicine

Management of Thromboembolic Disease

Updates in Aggressive Thrombotic Disease

Disorders of Platelet Destruction

Congenital Bleeding Disorders


Other Sources





Clinical Reasoning


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