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Critical Care Reviews Newsletter

November 25th 2012



Welcome to the 51st 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.

This week's research studies include a meta analysis suggesting APC did indeed lack clinical efficacy and was associated with increased bleeding, two studies on traumatic brain injury, including a demonstration of harm with both hyperoxia and hypoxia, a lack of efficacy for n-3-polyunsaturated fatty acids in the prevention of postoperative atrial fibrillation and further data from the MATTERs trial, this time supporting the combination of fibrinogen and anti-fibrinolytic therapy in trauma related haemorrhage.

Amongst the clinical review articles are papers on critical illness-related weakness, bispectral index, ventilator-associated pneumonia, weaning, cirrhosis, antibiotic resistance and two papers on palliation in ICU. There are 3 interesting articles from the New England Journal of Medicine, including commentaries on resident's hours, critical care in the developing world and a fascinating paper from 1846, describing the discovery of anaesthesia. This paper was voted by the journals readers as its most important publication ever.

The topic for This Week's Papers is haemorrhage, starting with a paper on the physiology of haemostasis in tomorrow's Paper of the Day.



Minerva Anestesiologica:     Activated Protein C

Lai et al performed an updated meta-analysis to generate a summary effect estimate and examine the reasons for outcome heterogeneity in placebo-controlled randomized clinical trials of APC on 28-day all-cause mortality in patients with severe sepsis or septic shock. Five placebo-controlled randomized clinical trials (n=7,260) were identified. APC was not associated with an improvement in 28-day all-cause mortality in patients with severe sepsis or septic shock (pAPC deaths: 736/3247 versus placebo deaths: 743/3341; pooled relative risk (RR) of 0.97 [95% CI 0.83-1.14]). The significant heterogeneity in the pooled RR for 28-day mortality (I2 value of 59.4%, F2 pvalue 0.043) was no longer present with exclusion of the post-study amendment portion of PROWESS (I2 value of 0%, F2 p-value 0.44 without PROWESS post-amendment). APC was associated with an increase in serious bleeding (pooled RR 1.48, 95% CI 1.10-1.99) but without an increase in intracranial haemorrhage (pooled RR 1.52, 95% CI 0.78-2.99).  Using meta-regression, the best ranked predictor of outcome heterogeneity was baseline mortality in the placebo arm, which was among the highest in PROWESS.

Full Text:  Lai. An updated meta-analysis to understand the variable efficacy of drotrecogin alfa, (activated) in severe sepsis and septic shock. Minerva Anestesiol 2012; Epublished November 22nd


Journal of the American Medical Association:     Traumatic Brain Injury

To determine whether citicoline can improve functional and cognitive status in people with traumatic brain injury (TBI), Zafonte et al performed a phase 3, double-blind randomized, placebo controlled trial in 1213 patients. Subjcets received either 90 days of 2g oral or enteral citicoline daily or placebo and were assessed at 90 days using the TBI-Clinical Trials Network Core Battery. There was no difference in rates of favorable improvement for the Glasgow Outcome Scale–Extended; citicoline: 35.4% versus placebo: 35.6%. The citicoline and placebo groups did not differ significantly at 90 days (global odds ratio [OR], 0.98 [95% CI, 0.83-1.15]); in addition, there was no significant treatment effect in the 2 severity subgroups (global OR, 1.14 [95% CI, 0.88-1.49] and 0.89 [95% CI, 0.72-1.49] for moderate/severe and complicated mild TBI, respectively). At the 180-day evaluation, the citicoline and placebo groups did not differ significantly with respect to the primary outcome (global OR, 0.87 [95% CI, 0.72-1.04]).

Abstract:  Zafonte. Effect of Citicoline on Functional and Cognitive Status Among Patients With Traumatic Brain Injury: Citicoline Brain Injury Treatment Trial (COBRIT). JAMA 2012;308(19):1993


Journal of the American Medical Association:     Atrial Fibrillation

To determine whether perioperative long-chain n-3-polyunsaturated fatty acids (n-3-PUFA) supplementation reduces atrial fibrillation after cardiac surgery, Mozaffarian et al completed an international multi-centre, double-blind, placebo-controlled, randomized clinical trial in 1516 patients.  Patients were randomized to receive fish oil (1-g capsules containing ≥840 mg n-3-PUFAs as ethyl esters) or placebo, with preoperative loading of 10 g over 3 to 5 days (or 8 g over 2 days) followed postoperatively by 2 g/d until hospital discharge or postoperative day 10, whichever came first.The mean patient age was 64 (SD, 13) years; 72.2% of patients were men, and 51.8% had planned valvular surgery. There was no difference in the occurance of atrial fibrillation: placebo 233 (30.7%) versus n-3-PUFAs 227 (30.0%); (odds ratio, 0.96 [95% CI, 0.77-1.20]; P = 0.74). None of the secondary end points were significantly different between the placebo and fish oil groups, including postoperative AF that was sustained, symptomatic, or treated (231 [30.5%] vs 224 [29.6%], P = .70) or number of postoperative AF episodes per patient (1 episode: 156 [20.6%] vs 157 [20.7%]; 2 episodes: 59 [7.8%] vs 49 [6.5%]; ≥3 episodes: 18 [2.4%] vs 21 [2.8%]) (P = 0.73). Supplementation with n-3-PUFAs was generally well tolerated, with no evidence for increased risk of bleeding or serious adverse events.

Abstract: Mozaffarian. Fish Oil and Postoperative Atrial Fibrillation: The Omega-3 Fatty Acids for Prevention of Post-operative Atrial Fibrillation (OPERA) Randomized Trial. JAMA 2012;308(19):2001


Archives of Surgery:     Traumatic Brain Injury

To investigate the relationship between oxygenation and short-term outcomes in patients with traumatic brain injury, Brenner and colleagues performed a retrospective review of 1547 consecutive patients with TBI who survived at least 12 hours after hospital admission. The majority of patients were male (77%) and had received blunt trauma (89%). Mean (SD) age, admission GCS score, and Injury Severity Score were 41.3 (20.6) years, 8.3 (4.7), and 31.9 (12.5), respectively. Mean (SD) intensive care unit length of stay and hospital length of stay were 8.7 (10.5) days and 13.8 (13.7) days, respectively. Mean (SD) discharge GCS score was 10.1 (4.7). The mortality rate was 28%. After controlling for several factors patients with hyperoxaemia had lower GCS at discharge, and those with either hyperoxaemia or hypoxaemia had higher mortality, than noroxaemic patients (all P< 0.05).

Abstract: Brenner. Association Between Early Hyperoxia and Worse Outcomes After Traumatic Brain Injury. Arch Surg 2012;147(11):1042 


Archives of Surgery:     Fibrinogen in Trauma

To evaluate the effect of fibrinogen-containing cryoprecipitate in addition to the antifibrinolytic tranexamic acid on survival in combat injuries, Morrison et al undertook a retrospective observational study in 1332 patients, whose data had been prospectively recorded by UK and US trauma registeries during treatment at a Role 3 Combat Surgical Hospital in Southern Afghanistan. All patients had required at least 1 unit of packed red blood cells and composed the following groups: tranexamic acid (n = 148), cryoprecipitate (n = 168), tranexamic acid/cryoprecipitate (n = 258), and no tranexamic acid/cryoprecipitate (n = 758). Injury Severity Scores were highest in the cryoprecipitate (n=168; mean [SD], 28.3 [15.7]) and tranexamic acid/cryoprecipitate (n=258; 26 [14.9]) groups compared with the tranexamic acid (n=148; 23.0 [19.2]) and no tranexamic acid/cryoprecipitate (n=758; 21.2 [18.5]) (P < .001) groups. Despite greater Injury Severity Scores and packed red blood cell requirements, mortality was lowest in the tranexamic acid/cryoprecipitate (11.6%) and tranexamic acid (18.2%) groups compared with the cryoprecipitate (21.4%) and no tranexamic acid/cryoprecipitate (23.6%) groups. Tranexamic acid and cryoprecipitate were independently associated with a similarly reduced mortality (odds ratio, 0.61; 95% CI, 0.42-0.89; P = 0.01 and odds ratio, 0.61; 95% CI, 0.40-0.94; P = 0.02, respectively). The combined tranexamic acid and cryoprecipitate effect vs neither in a synergy model had an odds ratio of 0.34 (95% CI, 0.20-0.58; P < 0.001), reflecting nonsignificant interaction (P = 0.21).

AbstractMorrison. Association of Cryoprecipitate and Tranexamic Acid With Improved Survival Following Wartime Injury. Findings From the MATTERs II Study. Arch Surg 2012; epublished November 19th


Critical Care:     Sepsis

Diaz-Martin and colleagues completed a multicenter study, analyzing all patients admitted to ICU who received antibiotics within the first six hours of diagnosis of severe sepsis or septic shock, in order to describe patterns of empirical antimicrobial therapy in severe sepsis, and to assess the impact of combination therapy including antimicrobials with different mechanisms of action on mortality. 1372 patients were evaluated 1022 of whom (74.5%) had community-acquired sepsis and 350 (25.5%) of whom had nosocomial sepsis. The most frequently prescribed antibiotic agents were ß-lactams (902, 65.7%) and carbapenems (345, 25.1%). Different class combination therapy (DCCT) was administered to 388 patients (28.3%) whereas non-DCCT therapy was administered to 984 (71.7%). The mortality rate was significantly lower in patients administered DCCT than in those administered non-DCCT (34% vs 40%; p=0.042).

Full Text:  Diaz-Martin. Antibiotic prescription patterns in the empirical therapy of severe sepsis: combination of antimicrobials with different mechanisms of action reduces mortality. Critical Care 2012;16:R223



New England Journal of Medicine:     Critical Care in Developing Nations


New England Journal of Medicine:     Resident Duty Hours


Review - Clinical


Journal of the Intensive Care Society:     Bispectral Index


Danish Medical Journal:     Critical Illness Polymyoneuropathy



European Cardiology:     Troponin Measurement


Drug Design, Development and Therapy:     Rivaroxaban


Molecules:     Ivabradine


Indian Journal of Pharmacology and Pharmacotherapeutics:     Istaroxime



Anesthesiology:     Ventilator-Associated Pneumonia


Journal of the Intensive Care Society:     Weaning



Alimentary Pharmacology:     Cirrhosis



Annals of Intensive Care:     Dialysis Catheters



Journal of the Intensive Care Society:     Antibiotic Resistance


Indian Journal of Medical Microbiology:     Antibiotic Resistance


Journal of the Intensive Care Society:     HIV


Mayo Clinic Proceedings:     Clostridium Difficile Infection



Journal of the Intensive Care Society:     Exertional Heat Stroke



Journal of the Intensive Care Society:     Palliative Care in ICU


Mayo Clinic Proceedings:     End-of-Life


Review - Basic Science

Review - Non-Clinical

Extreme Physiology & Medicine:     Clinician Profile


Journal of the Intensive Care Society:     Critical Care Research Costs


Special Article

New England Journal of Medicine:     Development of Anaesthesia



I hope you find these brief summaries and links useful.

Until next week