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Newsletter 122 / April 6th 2014

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Welcome to the 122nd 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.

This week's highlighted research studies include randomized controlled trials on the use of both aspirin and clonidine in non-cardiac surgery, plus bolus glucose for the treatment of hyperkalaemia; meta analyses address selective digestive decontamination, red cell transfusion-associated infections and adrenaline for out-of-hospital cardiac arrest; observational studies focus on non-invasive mechanical ventilation for acute respiratory failure, healthcare-associated infection prevalence, and CPR in ventilated patients; while additional studies investigate disorders of consciousness, subarachnoid haemorrhage monitoring, ARDS, acute pancreatitis, enteral feeding route, antimicrobial-resistant bacteria, haemorrhagic stroke, ECMO and traumatic brain injury. There is a new category commencing this week, following the correspondence of major studies and other items of interest, starting with the discussion around the TTM study.

There is a single position statement from the World Society of Emergency Surgery on the concept of abdominal sepsis, and also a single editorial addressing "Things to Stop Doing in the Intensive Care Unit to Limit Waste". There are two commentaries, a response from the Surviving Sepsis Campaign to the publication of the ProCESS trial, and a paper from JAMA on big data for future academia-industry collaboration; and several interesting case reports.

Amongst the clinical review articles are papers on non-invasive measurement of intra-cranial pressure, stroke thrombolysis, acute coronary syndromes, pleural ultrasound-guided interventions, kidney injury, haematological emergencies, procalcitonin, and penetrating torso injuries. The beginning of each month marks the addition of recently made open access articles from the major critical care journals, with 24 papers included.

If you prefer a break from all the journal reading, take a look at the general interest articles, where a newspaper report describes the hazards of conducting sensitive conversations at the bedside.

The topic for This Week's Papers is seizures, starting with a paper on refractory status epilepticus in tomorrow's Paper of the Day.

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Research

Randomized Controlled Trials

Devereaux and colleagues performed an international, multicentre, blinded, randomized, controlled, 2-by-2 factorial trial permitting separate evaluation of low-dose clonidine versus placebo and low-dose aspirin versus placebo in 10,010 patients with, or at risk for, atherosclerotic disease who were undergoing noncardiac surgery.

In the aspirin arm, patients were statified by those already receiving aspirin (continuation stratum, n=4382) or not (initiation stratum, n=5628), to the perioperative administration of aspirin or placebo. Patients started taking aspirin (at a dose of 200 mg) or placebo just before surgery and continued it daily (at a dose of 100 mg) for 30 days in the initiation stratum and for 7 days in the continuation stratum, after which patients resumed their regular aspirin regimen. The authors found:

no difference in the primary endpoint, a composite of death or nonfatal myocardial infarction at 30 days
- aspirin group: 7.0% (351/4998) versus placebo group: 7.1% (355/5012)
- hazard ratio in the aspirin group 0.99, 95% CI 0.86 to 1.15; P=0.92
increased major bleeding with aspirin
- 4.6% vs 3.8%, hazard ratio 1.23; 95% CI 1.01 to 1.49; P=0.04
no differences in 1° or 2° outcomes between aspirin strata

Full Text: Devereaux. Aspirin in Patients Undergoing Noncardiac Surgery (POISE-2 Trial). New Engl J Med 2014;epublished March 31st

In the clonidine arm, Deveraux compared low-dose clonidine (200 μg per day, commenced just before surgery and until 72 hours post surgery) with placebo, and found:

no difference in
- the primary endpoint, a composite of death or nonfatal myocardial infarction at 30 days
  - clonidine: n=367 vs placebo: n=339
  - hazard ratio with clonidine 1.08, 95% CI 0.93 to 1.26; p=0.29
clonidine was associated with increased incidence of
- myocardial infarction
  - clonidine 6.6% vs placebo 5.9%
  - hazard ratio with clonidine 1.11, 95% CI 0.95 to 1.30; P=0.18
- clinically important hypotension
  - 47.6% vs 37.1%
  - hazard ratio with clonidine 1.32; 95% CI 1.24 to 1.40; P<0.001
- nonfatal cardiac arrest
  - 0.3% (n=16) 0.1% (n=5)
  - hazard ratio 3.20; 95% CI 1.17 to 8.73; P=0.02

Abstract: Devereaux. Clonidine in Patients Undergoing Noncardiac Surgery (POISE 2 trial). N Engl J Med 2014;epublished March 31st

Chothia and colleagues compared the administration of 10 units of insulin with 100 ml of 50% glucose (50 g) with the administration of 100 ml of 50% glucose only in 10 chronic hemodialysis patients prone to hyperkalemia, and found:

both groups were hyperkalaemic at baseline:
- insulin group: serum [K⁺] 6.01 ± 0.87
- glucose-only group: serum [K⁺] 6.23 ± 1.20 mmol/l (p = 0.45)
at 60 minutes
- both groups had reductions in serum [K⁺]
  - insulin group: -0.83 ± 0.53 mmol/l (p < 0.001)
  - glucose-only group: -0.50 ± 0.31 mmol/l (p < 0.001)
- the insulin group had a lower serum [K⁺]
  - 5.18 ± 0.76 vs. 5.73 ± 1.12 mmol/l; p = 0.01
- two patients in the insulin group developed hypoglycemia

Abstract: Chothia. Bolus Administration of Intravenous Glucose in the Treatment of Hyperkalemia: A Randomized Controlled Trial. Canada Nephron Physiol 2014;126:1-8

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Meta Analysis

Price pooled data from 29 randomized, controlled trials evaluating selective digestive decontamination, selective oropharyngeal decontamination, or topical oropharyngeal chlorhexidine compared with standard care or placebo in general ICUs, and found:

decreased mortality was observed with
- selective digestive decontamination
  - odds ratio of 0.73 (95% CI 0.64 to 0.84)
- selective oropharyngeal decontamination
  - odds ratio 0.85 (0.74 to 0.97)
increased mortality was observed with
- chlorhexidine
  - odds ratio 1.25, 95% CI 1.05 to 1.50
comparing interventions
- both selective digestive decontamination and selective oropharyngeal decontamination were superior to chlorhexidine
- the difference between selective digestive decontamination and selective oropharyngeal decontamination was uncertain

Full Text: Price. Selective digestive or oropharyngeal decontamination and topical oropharyngeal chlorhexidine for prevention of death in general intensive care: systematic review and network meta-analysis. BMJ 2014;348:g2197

Rohde and colleagues reviewed data from 18 randomized controlled trials (n=7,593) evaluating whether red blood cell transfusion thresholds (restrictive vs liberal) are associated with the risk of infection, and whether this risk is independent of leukocyte reduction, and found:

a decreased risk of all serious infections with restrictive transfusion
- 11.8% (95% CI 7.0% to 16.7%) versus 16.9% (95% CI 8.9% to 25.4%)
  - risk ratio 0.82 (95% CI 0.72 to 0.95; I² = 0%; τ² <.0001)
  - NNT 38 (95% CI 24 to 122)
- the risk reduction with restrictive transfusion remained with leukocyte reduction
  - RR 0.80 (95% CI 0.67 to 0.95)
for trials with a restrictive hemoglobin threshold of <7.0 g/dL
- RR 0.82 (95% CI 0.70 to 0.97)
- NNT 20 (95% CI 12 to 133)
stratifying by patient type
- the risk reduction remained with
  - orthopaedic surgery: RR 0.70 (95% CI 0.54 to 0.91)
  - sepsis: RR 0.51 (95% CI 0.28 to 0.95)
- but not in
  - cardiac disease
  - the critically ill
  - acute upper gastrointestinal bleeding
  - infants with low birth weight

Abstract: Rohde. Health Care–Associated Infection After Red Blood Cell Transfusion. A Systematic Review and Meta-analysis. JAMA 2014;311(13):1317-1326

Lin et al pooled data from 14 randomized controlled trials (n=12,246) examining the efficacy of adrenaline in out-of-hospital cardiac arrest, and found:

standard dose adrenaline was associated with
- versus placebo (n=534)
  - improved
    - return of spontaneous circulation
      - RR 2.80, 95% CI 1.78 to 4.41, p < 0.001
    - survival to admission
      - RR 1.95, 95% CI 1.34 to 2.84, p < 0.001
- versus high dose adrenaline (n=6,174)
  - decreased
    - return of spontaneous circulation
      - RR 0.85, 95% CI 0.75 to 0.97, p = 0.02; I² = 48%
    - survival to admission
      - RR 0.87, 95% CI 0.76 to 1.00, p = 0.049; I² = 34%
- versus vasopressin alone (n=336)
  - no difference in outcomes
- versus vasopressin in combination with adrenaline (n=5,202)
  - no difference in outcomes
there was no survival to discharge or neurological outcome differences in any comparison group, including subgroup analyses

Abstract: Lin. Adrenaline for out-of-hospital cardiac arrest resuscitation: A systematic review and meta-analysis of randomized controlled trials. Resuscitation 2014;epublished March 15th

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Observational Studies

Schnell et al undertook a multicentre database study of 3,163 critically ill patients who required ventilatory support for acute respiratory failure between 1997 and 2011, examining the use and outcomes of non-invasive ventilation (n=1,232; 39%) versus first-line intubation, and found:

over the study period,
- first-line NIV increased from 29% to 42%
- NIV success rates increased from 69% to 84%
NIV decreased
- 60-day mortality
  - adjusted hazard ratio (aHR) 0.75; 95% CI 0.68 to 0.83; P < 0.0001
    - this protective effect was observed in patients with
      - acute-on-chronic respiratory failure (aHR 0.71; 95% CI 0.57 to 0.90; P = 0.004)
    - but not in patients with
      - cardiogenic pulmonary edema (aHR 0.85; 95% CI 0.70 to 1.03; P = 0.10)
      - hypoxemic acute respiratory failure
        
        immunocompetent (aHR 1.18; 95% CI 0.87 to 1.59; P = 0.30)
        
        immunocompromised (aHR 0.89; 95% CI 0.70 to 1.13; P = 0.35)
- fewer ICU-acquired infections
NIV failure was an independent time-dependent risk factor for mortality (aHR 4.2; 95% CI 2.8 to 6.2; P < 0.0001)

Abstract: Schnell. Noninvasive mechanical ventilation in acute respiratory failure: trends in use and outcomes. Intensive Care Med 2014;40(4):582-591

Magill et al completed a prevalence survey in 10 geographically diverse states (183 hospitals) to determine the prevalence of healthcare–associated infections in acute care hospitals and generate updated estimates of the national burden of such infections, and found:

of 11,282 patients, 452 had 1 or more health care–associated infections (4.0%; 95% CI 3.7 to 4.4)
of 504 such infections, the most common types were
- pneumonia (21.8%)
- surgical-site infections (21.8%)
- gastrointestinal infections (17.1%)
- device-associated infections (25.6%)
  - central-catheter–associated bloodstream infection
  - catheter-associated urinary tract infection
  - ventilator-associated pneumonia
Clostridium difficile was the most commonly reported pathogen
- 12.1% of health care–associated infections
extrapolating, it was estimated
- there were 648,000 patients with 721,800 health care–associated infections in U.S. acute care hospitals in 2011

Abstract: Magill. Multistate Point-Prevalence Survey of Health Care–Associated Infections. N Engl J Med 2014;370:1198-1208

Al-Alwan analyzed Medicare data from 1994 to 2005 to evaluate the outcomes, including long-term survival, after cardiopulmonary resuscitation in mechanically ventilated patients, and found:

471,962 patients received in-hospital CPR
- overall survival to hospital discharge of 18.4 % (95% CI 18.3 to 18.5% )
42,163 received CPR one or more days after mechanical ventilation initiation
- survival to hospital discharge after CPR in
  - ventilated patients: 10.1% (95% CI 9.8 to 10.4%)
  - non-ventilated patients: 19.2% (95% CI 19.1 to 19.3%) (p < 0.001)
- variables associated with decreased survival were
  - older age
  - race other than white
  - higher burden of chronic illness
  - admission from a nursing facility
- among all CPR recipients, those who were ventilated had 52% lower odds of survival
  - odds ratio 0.48, 95 % CI 0.46 to 0.49, p < 0.001
- median long-term survival
  - ventilated patients receiving CPR who survived to hospital discharge
    - 6.0 months (95% CI 5.3 to 6.8 months)
  - non-ventilated patients receiving CPR
    - 19.0 months (95% CI 18.6 to 19.5 months) (p < 0.001 by logrank test)
- of all patients receiving CPR while ventilated, only 4.1% were alive at 1 year