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Critical Care Reviews Newsletter

November 18^th 2012

Welcome

Hello

Welcome to the 50th 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.

Celebrating a half century of newsletters, and almost 1 year of bringing you the best critical care research from the literature, Critical Care Reviews has organised a free review meeting, with 8 eminent intensivists from Northern Ireland talking about the most important clinical trials published in 2012. Put the date of January 22nd in your diary. Further details to follow shortly.

This week's research studies include a report of improving outcomes following inhospital cardiac arrest, superior outcomes with the use of recombinant human relaxin-2 in acute heart failure, a suggestion following meta analysis that probiotics may decrease the incidence of clostridium difficile associated-diarrhoea and a paper describing the international epidemiology of bloodstream infections.

Recently published guidelines come from the American College of Cardiology Foundation, on the interpretation of troponin measurements, and from Croatia, on the application of therapeutic plasma exchange. There are editiorials on the perioperative use of oxygen and on a recently highlighted paper describing increased mortality with steroid use in sepsis, as recommended by the surviving sepsis campaign.

There are 26 free full text review articles from across the medical literature. Amongst these are papers on disorders of consciousness, mini-cardiopulmonary bypass, asthma, a number of papers on variceal haemorrhage, haemodialysis, porphyria and regional anaesthesia in ICU.

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

Research

New England Journal of Medicine: Cardiac Arrest

To determine whether survival and neurologic function after in-hospital cardiac arrest have improved over time, Girota et al interogated the Get with Guidelines–Resuscitation Registry from 2000 and 2009. In 374 hospitals, 84,625 hospitalized patients had a cardiac arrest, with 79.3% had an initial rhythm of asystole or pulseless electrical activity, and 20.7% had ventricular fibrillation or pulseless ventricular tachycardia. The proportion of cardiac arrests due to asystole or pulseless electrical activity increased over time (P<0.001 for trend). Risk-adjusted rates of survival to discharge increased from 13.7% in 2000 to 22.3% in 2009 (adjusted rate ratio per year, 1.04; 95% CI, 1.03 to 1.06; P<0.001 for trend). Survival improvement was similar in the two rhythm groups and was due to improvement in both acute resuscitation survival and postresuscitation survival. Rates of clinically significant neurologic disability among survivors decreased over time, with a risk-adjusted rate of 32.9% in 2000 and 28.1% in 2009 (adjusted rate ratio per year, 0.98; 95% CI, 0.97 to 1.00; P=0.02 for trend).

Abstract: Girotra. Trends in Survival after In-Hospital Cardiac Arrest. N Engl J Med 2012;367:1912-192

Lancet: Acute Heart Failure

Teerlink et al performed an international, double-blind, placebo-controlled trial, investigating Serelaxin (recombinant human relaxin-2) in 1161 patients admitted to hospital for acute heart failure. Serelaxin (n=581) improved one primary outcome of change from baseline dyspnoea score, as measured with a visual analog scale (448 mm × h, 95% CI 120—775; p=0·007), but not the other primary outcome of effect on the proportion of patients with moderate or marked dyspnoea improvement measured by Likert scale during the first 24 hours (Likert scale; placebo: 150 patients [26%]; serelaxin: 156 [27%]; p=0·70). No significant effects were recorded for the secondary endpoints of cardiovascular death or readmission to hospital for heart failure or renal failure (placebo: 75 events [60-day Kaplan-Meier estimate, 13·0%]; serelaxin: 76 events [13·2%]; hazard ratio [HR] 1·02 [0·74—1·41], p=0·89] or days alive out of the hospital up to day 60 (placebo: 47·7 [SD 12·1] days; serelaxin: 48·3 [11·6]; p=0·37). Serelaxin treatment was associated with significant reductions of other prespecified additional endpoints, including fewer deaths at day 180 (placebo: 65 deaths; serelaxin: 42; HR 0·63, 95% CI 0·42—0·93; p=0·019).

Abstract: Teerlink. Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure (RELAX-AHF): a randomised, placebo-controlled trial. Lancet 2012; epublished November 7th

Annals of Internal Medicine: C. Diff Diarrhoea

Johnstone et al undertook a systematic review and meta analysis, including 20 trials (n=3818), to assess the efficacy and safety of probiotics for the prevention of Clostridium difficile–associated diarrhea (CDAD) in adults and children receiving antibiotics. Probiotics reduced the incidence of CDAD by 66% (pooled relative risk, 0.34 [95% CI, 0.24 to 0.49]; I² = 0%). In a population with a 5% incidence of antibiotic-associated CDAD (median control group risk), probiotic prophylaxis would prevent 33 episodes (CI, 25 to 38 episodes) per 1000 persons. Of probiotic-treated patients, 9.3% experienced adverse events, compared with 12.6% of control patients (relative risk 0.82 [CI, 0.65 to 1.05]; I² = 17%). In 13 trials, data on CDAD were missing for 5% to 45% of patients, although results were robust to worst-plausible assumptions regarding event rates in studies with missing outcome data.

Abstract: Johnston. Probiotics for the Prevention of Clostridium difficile–Associated Diarrhea: A Systematic Review and Meta-analysis. Ann Intern Med 2012; epublished November 13th

Intensive Care Medicine: Hospital-Acquired Bloodstream Infections

Tabah et al undertook a prospective, multicentre non-representative cohort study in 162 ICUs in 24 countries to investigate the epidemiology of hospital-acquired bloodstream infections (HA-BSIs) and evaluated the impact of drug resistance on outcomes of critically ill patients. 1,156 patients with with HA-BSIs were enrolled, with 76 % of infections being ICU-acquired. The median time to diagnosis was 14 [IQR: 7–26] days after hospital admission. 12% of infections were polymicrobial. Of monomicrobial infections, 58.3 % were gram-negative, 32.8 % gram-positive, 7.8 % fungal and 1.2 % due to strict anaerobes. Overall, 629 (47.8 %) isolates were multidrug-resistant (MDR), including 270 (20.5 %) extensively resistant (XDR), and 5 (0.4 %) pan-drug-resistant (PDR). Micro-organism distribution and MDR occurrence varied significantly (p < 0.001) by country. The 28-day all-cause fatality rate was 36 %. In a multivariable model, independent predictors of 28-day mortality included MDR isolate [OR: 1.49; 95 % CI: 1.07–2.06], uncontrolled infection source (OR: 5.86; 95 % CI: 2.5–13.9) and timing to adequate treatment (before day 6 since blood culture collection versus never, OR 0.38; 95 % CI: 0.23–0.63; since day 6 versus never, OR 0.20; 95 % CI: 0.08–0.47).

Abstract: Tabah. Characteristics and determinants of outcome of hospital-acquired bloodstream infections in intensive care units: the EUROBACT International Cohort Study. Intensive Care Medicine 2012;38,12:1930-1945

Critical Care: Ventilator-Associated Pneumonia

Kollef et al undertook a prospective, double-blinded, randomized trial comparing a fixed 7-day course of doripenem (1 gram as a 4-hour infusion every 8 hours) with a fixed 10-day course of imipenem-cilastatin (1 gram as a 1-hour infusion every 8 hours) in 274 patients with ventilator-associated pneumonia (VAP) due to Gram-negative bacteria. The study was stopped prematurely at the recommendation of the Independent Data Monitoring Committee. There was no difference at the end of therapy in the microbiological intent-to-treat (MITT) analysis (doripenem: 45.6% vs imipenem-cilastatin: 56.8%; 95% CI, -26.3% to 3.8%). Similarly, there was no difference in clinical cure for patients with Pseudomonas aeruginosa VAP, the most common Gram-negative pathogen (doripenam: 41.2% versus imipenem-cilastatin: 60.0%; 95% CI, -57.2 to 19.5). There was no difference in all cause 28-day mortality in the MITT analysis (doripenam: 21.5% versus imipenem-cilastatin: 14.8%; 95% CI, -5.0 to 18.5). Doripenam was superior to imipenem-cilastatin as therapy for Pseudomonas aeruginosa VAP (doripenam: 35.3% versus imipenem-cilastatin: 0.0%; 95% CI, 12.6 to 58.0).

Full Text: Kollef. A randomized trial of 7-day doripenem versus 10-day imipenem-cilastatin for ventilator-associated pneumonia. Critical Care 2012; 16:R218