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Critical Care Reviews Newsletter

April 8th 2013



Welcome to the 70th 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.

It's been a quiet week for research publications, with the most significant studies being observational or meta analytic. A randomized controlled trial in cardiothoracic surgery has demonstrated increased organ failure with staph aureus vaccination, and increased mortality in those who developed staph aureus infection. Seperate meta analyses revealed worsened outcomes with reduced postoperative glomerular filtration rate, a lack of clear efficacy for interventions to optimise management of brain-dead donors.

This week's guideline is from the Australian National Blood Authority, which has published a very interesting and extensive paper on blood management in critical care. There are editiorials on massive transfusion and oxygen therapy plus commentaries on biomedical research and the case of an apparent cure from HIV infection. The CARRESS-HF trial is critiqued in a paper from the American Journal of Kidney Disease.

Amongst the clinical review articles are a series of papers from Blood Purification on extracorporeal therapies, including therapy for renal failure, liver failure, respiratory failure and sepsis. Additionally, the next batch of recently made open access review articles from the major journals are included, as well as a series of papers on death and organ donation from the British Journal of Anaesthesia.

The topic for This Week's Papers is organ dysfunction-induced organ failure, starting with a paper on heart-lung interactions in today's Paper of the Day.

If you want something of more general interest, try a fascinating post-mortem analysis, including images, of Albert Einstein's brain.



Anaesthesiology:     Postoperative Glomerular Filtration Rate

Mooney and colleagues performed a systematic review and meta-analysis to explore the relationship between estimated glomerular filtration rate (eGFR) and adverse outcomes after surgery. Forty-six studies were included, of which 44 focused exclusively on cardiac and vascular surgery. Within 30 days of surgery, eGFR less than 60 ml·min·1.73 m−2 was associated with a threefold increased risk of death (multivariable adjusted relative risk 2.98; 95% CI 1.95–4.96) and acute kidney injury (adjusted RR 3.13; 95% CI 2.22–4.41). An eGFR less than 60 ml·min·1.73 m−2 was associated with an increased risk of all-cause mortality (adjusted RR 1.61; 95% CI 1.38–1.87) and major adverse cardiovascular events (adjusted RR 1.49; 95% CI 1.32–1.67) during long-term follow-up. There was a nonlinear association between eGFR and the risk of early mortality such that, compared with patients having an eGFR more than 90 ml·min·1.73 m−2 the pooled RR for death at 30 days in those with an eGFR between 30 and 60 ml·min·1.73 m−2 was 1.62 (95% CI 1.43–1.80), rising to 2.85 (95% CI 2.49–3.27) in patients with an eGFR less than 30 ml·min·1.73 m−2 and 3.75 (95% CI 3.44–4.08) in those with an eGFR less than 15 ml·min·1.73 m−2. Conclusion: There is a powerful relationship between eGFR, and both short- and long-term prognosis after, predominantly cardiac and vascular, surgery.

Full Text:  Mooney. Preoperative Estimates of Glomerular Filtration Rate as Predictors of Outcome after Surgery: A Systematic Review and Meta-analysis. Anesthesiology 2013;118(4):809-824


Critical Care:     Septic Shock Epidemiology

Quenot and colleagues undertook a prospective, multicenter, observational cohort study in 14 French ICUs to investigate prognostic factors associated with 28-day mortality in septic shock patients.  Among 10,941 patients admitted to participating ICUs between October 2009 and September 2011, 1495 (13.7%) patients presented inclusion criteria for septic shock and were included. Invasive mechanical ventilation was needed in 83.9% (n=1248), inotropes in 27.7% (n=412), continuous renal replacement therapy in 32.5% (n=484) and hemodialysis in 19.6% (n=291). Mortality at 28 days was 42% (n=625). Variables associated with time to mortality, right-censored at day 28: age (for each additional 10 yrs) (hazard ratio 1.29; 95% CI: 1.20-1.38), immunosuppression (HR 1.63; 95% CI: 1.37-1.96), Knaus class C/D score versus class A/B score (HR 1.36; 95% CI: 1.14-1.62) and Sepsis-related Organ Failure Assessment (SOFA) score (HR 1.24 for each additional point; 95% CI: 1.21-1.27). Patients with septic shock and renal/urinary tract infection had a significantly longer time to mortality (HR=0.56; 95% CI: 0.42-0.75). Conclusion: Septic shock is common and carries high mortality in general intensive care unit populations.

Full Text:  Quenot. The epidemiology of septic shock in French intensive care units: the prospective multicenter cohort EPISS study. Critical Care 2013;17:R65


Respiratory Care:     Ventilation in ARDS

Chang and colleagues performed a secondary analysis of a multicenter cohort study (LIPS) of adult subjects at risk of lung injury with and without ALI/ARDS at onset of invasive ventilation to examine factors associated with choice of set tidal volumes (VT), and whether VT < 8 mL/kg predicted body weight related to the development of ALI/ARDS. Of 829 mechanically ventilated patients, 107 met the criteria for ALI/ARDS at time of intubation, and 161 developed ALI/ARDS after intubation (post-intubation ALI/ARDS). The median VT was 7.96 (IQR 7.14–8.94) mL/kg PBW in ALI/ARDS subjects, and 8.45 (IQR 7.50–9.55) mL/kg PBW in subjects without ALI/ARDS (P = .004). VT decreased from 8.40 (IQR 7.38–9.37) mL/kg PBW to 7.97 (IQR 6.90–9.23) mL/kg PBW (P < .001) in those developing post-intubation ALI/ARDS. Among subjects without ALI/ARDS, VT ≥ 8 mL/kg PBW was associated with shorter height and higher body mass index, while subjects with pneumonia were less likely to get ≥ 8 mL/kg PBW. Initial VT ≥ 8 mL/kg PBW was not associated with the post-intubation ALI/ARDS (adjusted odds ratio 1.30, 95% CI 0.74–2.29) or worse outcomes. Post-intubation ALI/ARDS subjects had mortality similar to subjects intubated with ALI/ARDS. Conclusion: Clinicians seem to respond to ALI/ARDS by lowering VT; initial VT, however, was not associated with the development of post-intubation ALI/ARDS or other outcomes.

Full Text: Chang. Contemporary Ventilator Management in Patients With and at Risk of ALI/ARDS. Respir Care, April 2013 58:578-588 


Journal of the American Medical Association:     Staph Aureus Vaccination

To evaluate the efficacy and safety of preoperative vaccination in preventing serious postoperative S aureus infection in cardithoracic surgery, Fowler et al undertook a multi-centre, international, double-blind, randomized, event-driven trial in 8031 adult cardiothoracic surgery patients.Participants were randomly assigned to receive a single 0.5-mL intramuscular injection of either V710 vaccine (n = 4015), or placebo (n = 4016).The independent data monitoring committee recommended termination of the study after the second interim analysis because of safety concerns and low efficacy. The V710 vaccine did not significantly reduce staph bacteraemias or deep sternal wound infections (22/3528 V710 vaccine recipients [2.6 per 100 person-years] vs 27/3517 placebo recipients [3.2 per 100 person-years]; relative risk: 0.81; 95% CI: 0.44-1.48; P = 0.58) or secondary end points of all S aureus surgical site and invasive infections at day 90 post-op. Compared with placebo, the V710 vaccine was associated with more adverse experiences during the first 14 days after vaccination (1219/3958 vaccine [30.8%; 95% CI: 29.4%-32.3%] and 866/3967 placebo [21.8%; 95% CI: 20.6%-23.1%], including 797 [20.1%; 95% CI: 18.9%-21.4%] and 378 [9.5%; 95% CI: 8.6%-10.5%] with injection site reactions and 66 [1.7%; 95% CI, 1.3%-2.1%] and 51 [1.3%; 95% CI: 1.0%-1.7%] with serious adverse events, respectively) and a significantly higher rate of multiorgan failure during the entire study (31 vs 17 events; 0.9 [95% CI: 0.6-1.2] vs 0.5 [95% CI: 0.3-0.8] events per 100 person-years; P = 0.04). Although the overall incidence of vaccine-related serious adverse events (1 in each group) and the all-cause mortality rate (201/3958 vs 177/3967; 5.7 [95% CI: 4.9-6.5] vs 5.0 [95% CI: 4.3-5.7] deaths per 100 person-years; P = 0.20) were not statistically different between groups, the mortality rate in patients with staphylococcal infections was significantly higher among V710 vaccine than placebo recipients (15/73 vs 4/96; 23.0 [95% CI: 12.9-37.9] vs 4.2 [95% CI: 1.2-10.8] per 100 person-years; difference, 18.8 [95% CI: 8.0-34.1] per 100 person-years). Conclusion: Staph aureus vaccination in patients undergoing cardiothoracic surgery with median sternotomy did not reduce the rate of serious postoperative S aureus infections and was associated with increased mortality among patients who developed S aureus infections.

Abstract:  Fowler. Effect of an Investigational Vaccine for Preventing Staphylococcus aureus Infections After Cardiothoracic Surgery. A Randomized Trial. JAMA 2013;309(13):1368-1378


Transplantation:     Management of the Brain-Dead Organ Donor

Rech et al performed a systematic review and meta-analysis to assess the efficacy of interventions to stabilize hemodynamics in brain-dead donors or to improve organ function and outcomes of transplantation.  Of 5096 articles retrieved, 39 randomized controlled trials were selected, with 20 being included in a qualitative synthesis, providing data on 1277 patients. The main interventions described were desmopressin use, triiodothyronine and methylprednisolone replacement, fluid management, vasopressor therapy, mechanical ventilation strategies, and surgical techniques. Three meta-analyses were conducted: the first included two studies and showed that desmopressin administered to brain-dead patients was not advantageous with respect to early organ function in kidney recipients (relative risk 0.97; 95% CI 0.85–1.10; I2=0%; P=0.809). The second included four studies and showed that triiodothyronine did not add hemodynamic benefits versus standard management (weighted mean difference 0.15; 95% CI −0.13 to 0.42; I2=17.4%; P=0.304). The third meta-analysis (two studies) showed that ischemic liver preconditioning during harvesting procedures did not benefit survival (relative risk 1.0; 95% CI 0.93–1.08; I2=0%; P=0.459). Conclusion: The present results suggest limited efficacy of interventions focusing on the management of brain-dead donors.

Abstract: Rech. Management of the Brain-Dead Organ Donor: A Systematic Review and Meta-Analysis. Transplantation 2013;95(7):966-974


British Medical Journal:     Traumatic Brain Injury Biomarker

Full Text: Mercier. Predictive value of S-100β protein for prognosis in patients with moderate and severe traumatic brain injury: systematic review and meta-analysis. BMJ 2013;346:f1757



National Blood Authority Australia:     Blood Management in Critical Care

Patient Blood Management Guidelines: Module 4 Critical Care; epublished April 5th 2013



Current Opinion in Anesthesiology:     Traumatic Coagulopathy


Translational Respiratory Medicine:     High FiO2 Therapy


Study Critique

American Journal of Kidney Disease:     CARRESS-HF



Journal of the American Medical Association:     Biomedical Research


Nature Medicine:     HIV Cure


Review - Clinical


Bangladesh Critical Care Journal:     Critical Illness Neuromuscular Complications


Neurosurgical Focus:     Intracerebral Haemorrhage Imaging


Blood Purification:     Cardiorenal Syndrome


Cardiorenal Medicine:     Cardiorenal Syndrome



Anaesthesiology:     Postoperative Respiratory Muscle Dysfunction

Pulmonary Circulation:     Pulmonary Hypertension


American Journal of Kidney Diseases:     Pulmonary Hypertension in Chronic Kidney Disease


Blood Purification:     Extracorporeal Carbon Dioxide Removal



Blood Purification:     Extracorporeal Liver Support



Open Journal of Nephrology:     Acute Kidney Injury Biomarkers


Blood Purification:     Renal Replacement Therapy


Blood Purification:     RRT in End Stage Renal Failure


Blood Purification:     Peritroneal Dialysis


Blood Purification:     Cellular Therapy for Acute Kidney Injury


Blood Purification:     Paediatric Renal Replacement Therapy



Journal of Thyroid Research:     Thyroid Hormone-Induced Cardioprotection



Current Opinion in Anesthesiology:     Massive Transfusion


Thrombosis Journal:     Heparin-Induced Thrombocytopaenia


Polish Archives of Internal Medicine:     Surgery during Anticoagulation


Drug Design, Development and Therapy:     Tedizolid 


Blood Purification:     Cytokine Adsorption



Korean Journal of Internal Medicine:     Carbon Monoxide

Recently Made Open Access Articles from Major Journals

American Journal of Respiratory and Critical Medicine:


Critical Care:   




Critical Care and Resuscitation:


British Journal of Anaesthesia:


BJA Supplement on Death


General Interest

Brain:     Albert Einstein's Brain


I hope you find these brief summaries and links useful.

Until next week