Newsletter 103 / November 24th 2013




Welcome to the 103rd 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.

Despite a supplementary newsletter earlier this week, this week's research studies are still dominated by trials presented at the American Heart Association conference in Dallas, and include randomized investigations into acute heart failure and acute coronary syndrome, as well as non-AHA studies examining traumatic brain injury and contrast-induced nephropathy. Meta analyses focus on hydroxyethyl starches, healthcare-associated pneumonia and coronary revascularization. Observational studies focus on intraoperative β-blocker therapy, procedural pain in ICU and out-of-hospital cardiac arrest.

This week's guidelines look at transport of the critically ill, airway clearance and obesity. There is one editorial on goal-directed therapy in cardiac surgery, and multiple commentaries addressing asthma, terrorist events, scientific interpretation, antibiotic resistance, desmopressin for surgical haemorrhage, and muscle wasting.

Amongst the clinical review articles are papers on the blood brain barrier, stroke thrombolysis in the elderly, acute coronary syndrome, preoperative cardiac evaluation, respiratory burns, abdominal radiography, interstitial nephritis, perioperative organ injury, anaesthetic management of the septic patient and ultrasound. There's even a couple of papers from me, on fluids and acute lung injury.

The topic for This Week's Papers is thoracic trauma, starting with an article on CT imaging in tomorrow's Paper of the Day.

The medical students at Queens University Belfast are trying to raise funds for hospitals in less developed healthcare systems - check out this fantastic video and considering sponsoring a good cause.



Critical Care Reviews Meeting January 24th, 2014 - Belfast, Northern Ireland

For the second year, Critical Care Reviews will be hosting a not-for-profit meeting discussing the major critical care studies published in the past 12 months. In addition, there will be updates in haematology, hepatology and microbiology, as well as key note presentations from international guest speakers Prof Alistair Nichol (Dublin/Melbourne), Prof Mervyn Singer (London) and Prof John Marshall (Toronto). 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.

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.


SMACC GOLD March 19-21st, 2014 Gold Coast, Queensland, Australia

This major international conference, also in it's second year, is a must for those active in the online critical care community. Webmasters of the most prominent critical care websites and blogs will descend on the beautiful Gold Coast for an amazing get together of like-minded people in a totally different style of conference. 



Randomized Controlled Trials

Journal of the American Medical Association:     Renal Dysfunction in Heart Failure

Chen et al undertook a multicenter, double-blind, randomized, placebo-controlled trial in 360 hospitalized patients with acute heart failure and renal dysfunction (estimated glomerular filtration rate of 15-60 mL/min/1.73 m2), evaluating the addition to diuretic therapy of either low-dose dopamine (2 μg/kg/min) (n = 122), low-dose nesiritide (0.005 μg/kg/min without bolus) (n = 119) or placebo (n = 119), and found: 
  1. Compared with placebo
    • low-dose dopamine had no significant effect on
      • 72-hour cumulative urine volume
        • dopamine 8524 mL (95% CI 7917-9131) vs placebo 8296 mL (95% CI 7762-8830) 
        • difference 229 mL; 95% CI −714 to 1171; P = 0.59
      • change in cystatin C level
        • dopamine 0.12 mg/L (95% CI 0.06-0.18) vs placebo 0.11 mg/L (95% CI 0.06-0.16)
        • difference 0.01; 95% CI −0.08 to 0.10; P= 0.72
    • low-dose nesiritide had no significant effect on
      • 72-hour cumulative urine volume
        • nesiritide 8574 mL (95% CI 8014-9134) vs placebo 8296mL (95% CI 7762-8830)
        • difference 279 mL; 95% CI −618 to 1176 mL; P = 0.49 
      • change in cystatin C level
        • nesiritide 0.07 mg/L (95% CI 0.01-0.13) vs placebo 0.11 mg/L (95% CI, 0.06-0.16)
        • difference −0.04; 95% CI −0.13 to 0.05; P=0.36
    • no effect of low-dose dopamine or nesiritide on secondary end points reflective of decongestion, renal function, or clinical outcomes
Full Text:  Chen. Low-Dose Dopamine or Low-Dose Nesiritide in Acute Heart Failure With Renal Dysfunction. The ROSE (Renal Optimization Strategies Evaluation) Acute Heart Failure Randomized Trial JAMA 2013;epublished November 18th 

Journal of the American Medical Association:     Acute Coronary Syndrome

Nicholls and colleagues completed an international, double-blind, randomized trial in 5,145 patients randomized within 96 hours of presentation with an acute coronary syndrome, comparing varespladib 500mg (n = 2,572), a secretory phospholipase A2 inhibitor which has favorable effects on lipid and inflammatory markers, with placebo (n = 2,573) for 16 weeks, and found:

  1. the independent data and safety monitoring board recommended termination of the trial for futility and possible harm at a prespecified interim analysis
  2. varespladib was associated with
    • no difference in the incidence of the primary efficacy, a composite of cardiovascular mortality, nonfatal myocardial infarction, nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks
      • varespladib 6.1% versus placebo 5.1% (hazard ratio 1.25; 95% CI 0.97-1.61; log-rank P =0.08)
    • an increased risk of myocardial infarction with varespladib
      • (3.4% vs 2.2%; HR 1.66; 95% CI 1.16-2.39; log-rank P  = 0.005)
    • an increased risk of the composite secondary end point of cardiovascular mortality, MI, and stroke
      • 4.6% vs 3.8%; HR 1.36; 95% CI 1.02-1.82; P= 0.04

Full Text:  Nicholls. Varespladib and Cardiovascular Events in Patients With an Acute Coronary SyndromeThe VISTA-16 Randomized Clinical Trial. JAMA 2013;epublished November 18th  


BMC Emergency Medicine:     Traumatic Brain Injury

Yutthakasemsunt and colleagues completed a double blinded, placebo controlled, randomized trial, evaluating early administration of tranexamic acid (n=120) in 238 patients with moderate to severe traumatic brain injury, and found:

  1. no differences in
    • the incidence of progressive intracranial haemorrhage
      • tranexamic acid 18% versus 27% (RR = 0.65; 95% CI 0.40 to 1.05)
    • the risk of all-cause death
      • tranexamic acid vs placebo: RR 0.69; 95% CI 0.35 to 1.39
    • risk of unfavourable Glasgow Outcome Scale 
      • tranexamic acid vs placebo: RR 0.76; 95% CI 0.46 to 1.27
  2. no evidence of increased risk of thromboembolic events in those patients allocated to TXA

Full Text:  Yutthakasemsunt. Tranexamic acid for patients with traumatic brain injury: a randomized, double-blinded, placebo-controlled trial. BMC Emergency Medicine 2013;13:20


JAMA Internal Medicine:     Acute Coronary Syndrome

de Mulder and colleagues performed a single-center, prospective, open-label, randomized clinical trial in 294 patients with acute coronary syndrome and an admission plasma glucose level of 140 to 288 mg/dL, and without insulin dependent diabetes mellitus, comparing an intensive glucose management strategy, aiming at a plasma glucose level of 85 to 110 mg/dL by using intravenous insulin, with a conventional expectative glucose management strategy, and found:

  1. no difference in serum biomarkers
    • median high-sensitivity troponin T values at 72 hours
      • intensive management 1,197 ng/L (IQR 541-2,296 ng/L) vs conventional arm 1,354 ng/L (530-3,057 ng/L) (P=0.41)
    • median AUC CK-MB
      • intensive management 2,372 U/L (1,242-5,004 U/L) vs 3,171 U/L (1,620-5,337 U/L) (P = 0.18)
  2. no significant difference in median extent of myocardial injury as measured by myocardial perfusion scintigraphy (2% vs 4%; P=0.07)
  3. severe hypoglycemia (<50 mg/dL) was rare and occurred in 13 patients
  4. intensive management was associated with increased risk of death or spontaneous second myocardial infarction (5.7% vs 0.7%; P=0.04)

Abstract:  de Mulder. Intensive Glucose Regulation in Hyperglycemic Acute Coronary Syndrome. Results of the Randomized BIOMarker Study to Identify the Acute Risk of a Coronary Syndrome–2 (BIOMArCS-2) Glucose Trial. JAMA Intern Med 2013;173(20):1896-1904


Journal of the American College of Cardiology:     Contrast-Induced Nephropathy

Han and colleagues completed a randomized controlled trial in 2,998 patients with type 2 diabetes mellitus and chronic kidney disease, comparing rosuvastatin 10 mg/day (n=1,498) for five days (two days before, three dayspost procedure) with standard care (n=1,500) for the prevention of contrast-induced acute kidney injury, and found:

  1. rosuvastatin was associated with a
    • reduced incidence of contrast-induced AKI
      • 2.3% vs 3.9%, P=0.01
      • OR=0.58, 95% CI 0.38, P=0.89
    • at day 30, reduced rates of worsening heart failure
      • 2.6% vs 4.3%;P=0.02

Abstract:  Han. Short-term rosuvastatin therapy for the prevention of contrast-induced acute kidney injury in patients with diabetes and chronic kidney disease. J Am Coll Cardiol 2013;epublished September 26th


Meta Analysis

Journal of Critical Care:     Hydroxyethyl Starch

Neto and colleagues pooled data from 10 trials (n=4,624) comparing hydroxyethyl starch fluid resuscitation with crystalloid fluid resuscitation in sepsis, and found:

  1. HES was associated with
    • an increased risk of
      • acute kidney injury (risk ratio 1.24, 95% CI 1.13-1.36)
      • renal replacement therapy requirement (RR 1.36, 95% CI 1.17-1.57)
      • red blood cell transfusion (RR 1.14, 95% CI 1.01-1.93)
      • 90-day mortality (RR 1.14, 95% CI 1.04-1.26)
    • no difference in the risk of
      • intensive care unit mortality (RR 0.74, 95% CI, 0.43-1.26)
      • 28-day mortality (RR 1.11, 95% CI 0.96-1.28)

Abstract:  Neto. Fluid resuscitation with hydroxyethyl starches in patients with sepsis is associated with an increased incidence of acute kidney injury and use of renal replacement therapy: A systematic review and meta-analysis of the literature. J Crit Care 2013;epublished November 21st


Clinical Infectious Diseases:     Healthcare-Associated Pneumonia

Chalmers and colleagues perfermed a systematic review and meta analysis, including 24 studies (n=22,456), evaluating the utility of the 2005 ATS/IDSA guideline defined “healthcare-associated pneumonia”  to identify patients at higher risk of antibiotic resistant pathogens, requiring broad spectrum therapy, and found:

  1. overall study quality was poor
  2. healthcare-associated pneumonia was associated with an increased odds ratio of
    • MRSA 4.72 (95% CI 3.69-6.04)  (p<0.0001)
    • enterobactericeae 2.11 (1.69-2.63) (p<0.0001)
    • P.aeruginosa 2.75 (2.04-3.72) (p<0.0001)
    • these analysis were confounded by publication bias
  3. the discriminatory ability of HCAP for resistant pathogens
    • all studies: AUC 0·70 (0·69-0·71)
    • high quality studies: AUC 0·66 (0·62-0·70) 
    • prospective studies: AUC 0·64 (0·62-0·66)
  4. HCAP was not associated with increased adjusted mortality (OR 1.20, 0.85-1.70; p=0.3)

Abstract:  Chalmers. Healthcare associated pneumonia does not accurately identify potentially resistant pathogens: a systematic review and meta-analysis. Clin Infect Dis 2013;epublished November 22nd


Journal of the American Medical Association:     Coronary Revascularization

Deb et al reviewed 13 randomized controlled trials and 5 meta analyses comparing the effectiveness of CABG and PCI in patients with unprotected left main disease (>50% left main coronary stenosis without protective bypass grafts), multivessel coronary artery disease, diabetes, or left ventricular dysfunction, and found:

  1. CABG should be recommended in
    • patients with unprotected left main disease, multivessel coronary artery disease, or left ventircular dysfunction, if the severity of coronary disease is deemed to be complex (SYNTAX >22)
    • patients with diabetes and multivessel coronary disease, irrespective of the severity of coronary anatomy
      • reduced 5-year all-cause mortality, myocardial infarction, stroke, and repeat revascularization
        • CABG 18.7% vs PCI 26.6%; P=0.005
  2. PCI should be considered for patients with
    • less complex coronary disease (SYNTAX ≤22)
    • higher surgical risk patients 
  3. the incidence of repeat revascularization is higher after PCI
  4. the incidence of stroke is higher after CABG surgery

Abstract:  Deb. Coronary Artery Bypass Graft Surgery vs Percutaneous Interventions in Coronary Revascularization. A Systematic Review. JAMA 2013;310(19):2086-2095


Observational Studies

JAMA Internal Medicine:     Intraoperative β-Blocker Therapy

Andersson et al completed a registery evaluation assessing the association of β-blocker treatment with major cardiovascular adverse events and all-cause mortality in 28,263 patients with ischemic heart disease undergoing noncardiac surgery, and found:

  1. 7,990 (28.3%) had heart failure and 20,273 (71.7%) did not have heart failure
    • β-Blockers were used in 4,262 (53.3%) with heart failure and 7,419 (36.6%) without
  2. β-blockers use was not associated with reductions in either
    • major cardiovascular adverse events hazard ratio 0.90 (95% CI 0.79-1.02)
    • all-cause mortality: HR 0.95 (95% CI 0.85-1.06)
  3. among patients with heart failure, β-blockade was associated with a significantly lower risk of
    • major cardiovascular adverse events (HR 0.75; 95% CI 0.70-0.87) 
    • all-cause mortality (HR 0.80; 0.70-0.92)
  4. among patients without heart failure
    • there was no significant association of β-blocker use with
      • major cardiovascular adverse events (HR 1.11; 0.92-1.33) 
      • mortality (HR 1.15; 0.98-1.35) (P < 0.001 for interactions)
    •  β-blockers were also associated with a lowered risk among those with a recent myocardial infarction (<2 years)
      • major cardiovascular adverse events: (HR 0.54; 95% CI 0.37-0.78) 
      • all-cause mortality (HR 0.80; 0.53-1.21) (P < 0.02 for interactions between β-blockers and time period after myocardial infarction)
      • no significant association in the remaining patients
  5. Results were similar in propensity score–matched analyses.

Abstract:  Andersson. Association of β-Blocker Therapy With Risks of Adverse Cardiovascular Events and Deaths in Patients With Ischemic Heart Disease Undergoing Noncardiac Surgery. A Danish Nationwide Cohort Study. JAMA Intern Med 2013;epublished November 18th


American Journal of Respiratory and Critical Care Medicine:     Procedureal Pain

Puntillo and colleagues completed a prospective, cross-sectional, multicenter, multinational study of pain intensity associated with 12 procedures in 3,851 patients who underwent 4,812 procedures, and found:
  1. pain intensity on a 0-10 numeric rating scale increased significantly from baseline pain during all procedures (P<0.001)
  2. the three most painful procedures were (median/IQR pain scores):
    • Chest tube removal 5 [3;7]
    • wound drain removal 4.5 [2;7]
    • arterial line insertion 4 [2;6]
  3. using multivariate analysis, risk factors independently associated with greater procedural pain intensity were
    • the specific procedure
    • opioid administration specifically for the procedure
    • pre-procedural pain intensity
    • pre-procedural pain distress
    • intensity of the worst pain on the same day, before the procedure
    • procedure not performed by a nurse
  4. a significant ICU effect was observed, with no visible effect of country due to its absorption by the ICU effect

Abstract:  Puntillo. Determinants of Procedural Pain Intensity in the Intensive Care Unit: The Europain Study. Am J Respir Crit Care Med 2013;epublished November 21st


Critical Care:     Out-of-Hospital Cardiac Arrest

Goto and colleagues completed an analysis of a prospective Japanese nationwide database of 398,121 adults suffering an out-of-hospital cardiac arrest and without a prehospital return of spontaneous circulation, and found:

  1. a rate of 1-month favourable Cerebral Performance Category scale 1-2 of 0.49%.
  2. using multivariate logistic regression analysis, the prehospital independent variables associated with CPC 1-2 were:
    • initial non-asystole rhythm
      • ventricular fibrillation (adjusted odds ratio 9.37; 95% CI 7.71 to 11.4)
      • pulseless ventricular tachycardia (aOR 8.50; 95% CI 5.36 to 12.9)
      • pulseless electrical activity (aOR 2.75; 95% CI 2.40 to 3.15)
    • age <65 years (aOR 3.90; 95% CI 3.28 to 4.67)
    • arrest witnessed by EMS personnel (aOR 2.82; 95% CI 2.48 to 3.19)
    • call-to-hospital arrival time <24 minutes (aOR 2.58; 95% CI 2.22 to 3.01)
    • arrest witnessed by any layperson
    • physician-staffed ambulance
    • call-to-response time <5 minutes
    • prehospital shock delivery
    • presumed cardiac cause

Full Text:  Goto. Neurological outcomes in patients transported to hospital without a prehospital return of spontaneous circulation after cardiac arrest. Critical Care 2013;17:R274


Other Studies of Interest


















I hope you find these brief summaries and links useful.

Until next week