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.
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.
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]).
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.
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).
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).
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
Journal of the Intensive Care Society: Bispectral Index
Danish Medical Journal: Critical Illness Polymyoneuropathy
- Ydemann. Treatment of critical illness polyneuropathy and/or myopathy - a systematic review. Dan Med J 2012;59(10):A4511
European Cardiology: Troponin Measurement
- Klingenberg. High-sensitivity Troponins – Difficult Friends in Acute Coronary Syndromes. European Cardiology 2012;8(3):181-5
Drug Design, Development and Therapy: Rivaroxaban
- Riccioni. Ivabradine: An Intelligent Drug for the Treatment of Ischemic Heart Disease. Molecules 2012;17:13592-13604
Indian Journal of Pharmacology and Pharmacotherapeutics: Istaroxime
Anesthesiology: Ventilator-Associated Pneumonia
- Rouby. Aerosolized Antibiotics for Ventilator-associated Pneumonia: Lessons from Experimental Studies. Anesthesiology 2012;117(6):1364–1380
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
- Choudhury. Emergence and dissemination of antibiotic resistance: A global problem. Indian J Med Microbiol 2012;30:384-90
Journal of the Intensive Care Society: HIV
- Jones. Guidance on occupational-related HIV post-exposure prophylaxis in the intensive care setting. JICS 2012;13(4):332-336
Mayo Clinic Proceedings: Clostridium Difficile Infection
- Khanna. Clostridium difficile Infection: New Insights Into Management. Mayo Clin Proc 2012;87(11):1106-1117
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
- Burkle. End-of-Life Care Decisions: Importance of Reviewing Systems and Limitations After 2 Recent North American Cases. Mayo Clin Proc 2012;87(11):1098-1105
Review - Basic Science
International Journal of Nephrology: Urotensin-II
- Balat. Urotensin-II: More Than a Mediator for Kidney. International Journal of Nephrology 2012;2012:249790
Review - Non-Clinical
Extreme Physiology & Medicine: Clinician Profile
Journal of the Intensive Care Society: Critical Care Research Costs
- Walsh. A guide to costing and funding intensive care trials in the United Kingdom. JICS 2012;13(4):279-288
New England Journal of Medicine: Development of Anaesthesia
- Bigelow. Insensibility during Surgical Operations Produced by Inhalation. Boston Med Surg J 1846; 35:309-317
I hope you find these brief summaries and links useful.
Until next week