ccr logo

Critical Care Reviews Newsletter

April 2nd 2013



Welcome to the 69th 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.

Firstly, a big thank you to Chris Nickson at Life in the Fast Lane for an extremely generous review of Critical Care Reviews. There has been a huge number of people registering, both on the site and on Twitter, as a result. I hope you all find this resource useful. Given the breadth of topics covered in the newsletter everyone should see a paper or two that they find interesting. I suggest just picking those articles, as there is too much to read. There will be another 100 papers along in a few days....

This week's research studies include investigations on selective digestive decontamination, nicotine replacement therapy, physical therapy, ARDS, chlorhexidine bathing, sepsis biomarkers, a follow up of the 6S study, acute kidney injury, natriuretic peptides, chelation therapy for coronary artery disease and recombinant factor VII.

This week's guidelines are from the American Heart Association on atrial fibrillation and from the American Association of Neurological Surgeons on acute spinal injuries.

There is the usual wide range of clinical review articles spanning all systems, with a concentration of great papers from the Methodist Debakey Cardiovascular Journal. In addition to the 51 review articles, there are 5 commentaries, 4 editorials and 1 position statement.

In honour of my Antipodean friends, the topic for This Week's Papers is something they, but not I, are likely to deal with - envenomation. Yesterday's Paper of the Day focused on the Funnel Web spider and today this theme continues, with a look at spider bites and toxindromes in general.



Lancet Infectious Disease

Daneman et al performed a systematic review (64 studies) of the effect of selective digestive decontamination (SDD) or selective oropharyngeal decontamination (SOD) on the rates of colonisation or infection with antimicrobial-resistant pathogens in critically ill patients. Comparing patients who received SDD or SOD versus controls who received no intervention, there was no difference in the prevalence of colonisation or infection with Gram-positive antimicrobial-resistant pathogens of interest, including meticillin-resistant Staphylococcus aureus (odds ratio 1·46, 95% CI 0·90—2·37) and vancomycin-resistant enterococci (0·63, 0·39—1·02). Among Gram-negative bacilli, there was no difference in aminoglycoside-resistance (0·73, 0·51—1·05) or fluoroquinolone-resistance (0·52, 0·16—1·68), but there was a reduction in polymyxin-resistant Gram-negative bacilli (0·58, 0·46—0·72) and third-generation cephalosporin-resistant Gram-negative bacilli (0·33, 0·20—0·52) in recipients of selective decontamination compared with those who received no intervention. Conclusion: SDD or SOD was not associated with the development of resistant pathogens in ICU patients, although the effect of decontamination on ICU-level antimicrobial resistance rates is understudied.

Abstract:  Daneman. Effect of selective decontamination on antimicrobial resistance in intensive care units: a systematic review and meta-analysis. Lancet Infectious Diseases 2013;13(4):328-341


Respiratory Care:     Nicotine Replacement in ICU

Pathak performed a randomized controlled double-blind prospective pilot study to examine the effects of nicotine replacement therapy (21mg patch daily) in 40 critically ill smokers. There were 27 male and 13 female patients. Mean age was 57.4 years in the interventional group and 52.5 years in the control group. Mean APACHE II score was 14.3 in the interventional group versus 13.8 in the control group. Mean length of ICU stay was 4.5 days in the interventional group, compared to 7 days in the control group. Mean number of days on ventilator was 1.9 in the interventional group versus 3.5 in the control group. Number of days on sedation/analgesia was less in the interventional group compared to the control group. Conclusion: Although the length of ICU stay and number of days on ventilator seemed to decrease numerically in this pilot study, statistically there was no beneficial effect demonstrated in patients receiving nicotine replacement therapy.

Full Text:  Pathak. Outcome of Nicotine Replacement Therapy in Patients Admitted to Intensive Care Unit: a Randomized Controlled Double-Blind Prospective Pilot Study. Respir Care 2013; epublished March 26th


Critical Care Medicine:     Physical Therapy in ICU

Kayambu and colleagues completed a systematic review, totaling ten randomized controlled trials, evaluating the efficacy of exercise in the critically ill. The mean Physiotherapy Evidence Database score was 5.4. Physical therapy was associated with improvements in quality of life (g = 0.40, 95% CI 0.08-0.71), physical function (g = 0.46, 95% CI 0.13-0.78), peripheral muscle strength (g = 0.27, 95% CI 0.02-0.52), and respiratory muscle strength (g = 0.51, 95% CI 0.12-0.89). Length of hospital (g = -0.34, 95% CI -0.53 to -0.15) and ICU stay (g = -0.34, 95% CI -0.51 to -0.18) significantly decreased and ventilator-free days increased (g = 0.38, 95% CI 0.16-0.59) following physical therapy in the ICU. There was no effect on mortality. Conclusion: Physical therapy in ICU appears to confer significant benefit, although larger controlled trials of better quality are required to verify the strength of these tentative associations.

Abstract:  Kayambu. Physical Therapy for the Critically Ill in the ICU: A Systematic Review and Meta-Analysis. Crit Care Med 2013;epublished March 22nd


Intensive Care Medicine:     Definition of ARDS

To test whether the use of PaO2/FiO2 ratio calculated with a standardised ventilatory setting within 24 h of ARDS diagnosis allows a more clinically relevant ARDS classification, Villar et al studied 452 ARDS patients enrolled prospectively in two independent, multicenter cohorts treated with protective mechanical ventilation. At the time of ARDS diagnosis, patients had a PaO2/FiO2 ≤ 200. In the derivation cohort (n = 170), PaO2/FiO2 was measured with two levels of PEEP (≥5 and ≥10 cmH2O) and two levels of FiO2 (≥0.5 and 1.0) at ARDS onset and 24 h later. Dependent upon PaO2 response, patients were reclassified into three groups: mild (PaO2/FiO2 > 200), moderate (PaO2/FiO2 101–200), and severe (PaO2/FiO2 ≤ 100) ARDS. The primary outcome measure was ICU mortality. The standard ventilatory setting that reached the highest significance difference in mortality among these categories was tested in a separate cohort (n = 282). The only standard ventilatory setting that identified the three PaO2/FiO2 risk categories in the derivation cohort was PEEP ≥ 10 cmH2O and FiO2 ≥ 0.5 at 24 h after ARDS onset (p = 0.0001). Using this ventilatory setting, patients in the validation cohort were reclassified as having mild ARDS (n = 47, mortality 17 %), moderate ARDS (n = 149, mortality 40.9 %), and severe ARDS (n = 86, mortality 58.1 %) (p = 0.00001). Conclusion: Standardising ventilatory settings for assessing PaO2/FiO2 improved risk stratification of ARDS patients. 

Abstract:  Villar. A universal definition of ARDS: the PaO2/FiO2 ratio under a standard ventilatory setting—a prospective, multicenter validation study. Intensive Care Med 2013;39(4):583-592


Lancet:     Chlorhexidine Bathing for Children

Milstone and colleagues performed an unmasked, cluster-randomised, two-period crossover trial in 4947 children comparing a daily bathing routine of either standard bathing practices or using a cloth impregnated with 2% chlorhexidine gluconate CHG, for a 6-month period. Units switched to the alternative bathing method for a second 6-month period. Although there was no difference in the intention-to-treat analysis (chlorhexidine bathing: 3·52 per 1000 days, 95% CI 2·64—4·61 versus standard bathing: 4·93 per 1000 days, 3·91—6·15; adjusted incidence rate ratio 0·71, 95% CI 0·42—1·20), in the per protocol analysis, there was a reduced incidence of bacteraemia in those receiving chlorhexidine bathing (3·28 per 1000 days, 2·27—4·58 versus standard bathing: 4·93 per 1000 days, 3·91—6·15; adjusted incidence rate ratio 0·64, 0·42—0·98). No serious study-related adverse events were recorded, and the incidence of CHG-associated skin reactions was 1·2 per 1000 days (95% CI 0·60—2·02).  Conclusion: Compared with standard daily bathing, chlorhexidine daily bathing was associated with a lower incidence of bacteraemias.

Abstract:  Milstone. Daily chlorhexidine bathing to reduce bacteraemia in critically ill children: a multicentre, cluster-randomised, crossover trial. Lancet 2013;381(9872):1099-1106


Critical Care:     Sepsis Biomarkers

Llewelyn et al assessed the performance of three potential sepsis biomarkers [pancreatic stone protein (PSP), soluble CD25 (sCD25) and heparin binding protein (HBP)] in 219 unselected patients at admission to intensive care to differentiate sepsis from non-infective systemic inflammatory response. Both PSP and sCD25 had an area under the receiver operating curve (AUC) greater than 0.9; PSP 0.927 (0.887-0.968) and sCD25 0.902 (0.854 - 0.949). Procalcitonin and IL6 also performed well as markers of sepsis whilst in this intensive care unit (ICU) population, HBP did not; PCT 0.840 (0.778 - 0.901), IL6 0.805 (0.739 - 0.870) and HBP 0.607 (0.519-0.694). Levels of both PSP and PCT reflected severity of illness and both markers performed well in differentiating patients with severe sepsis from severely ill patients with a non-infective systemic inflammatory response; AUCs 0.955 (0.909-1) and 0.837 (0.732-0.941) respectively. Although levels of sCD25 did not correlate with severity, addition of sCD25 to either PCT or PSP in a multivariate model improved the diagnostic accuracy of either marker alone. Conclusions:PSP and sCD25 perform well as sepsis biomarkers in patients with suspected sepsis at the time of admission to intensive or high dependency care

Full Text: Llewelyn. Sepsis biomarkers in unselected patients on admission to intensive or high-dependency care. Critical Care 2013;17:R60


Critical Care:     6S Follow Up - Effects of Hydroxyethyl Starch

Wittbrodt and colleagues performed a post hoc analyses of the Danish survivors (n=295) of the 6S trial using mailed questionnaires on self-perceived health-related quality of life. Patients were assessed at a median of 14 months (interquartile range 10 - 18) after randomization, with 182 (61%) and 185 (62%) completing questionnaires for the assessment of health-related quality of life and pruritus, respectively. Patients who received hydroxyethyl starch had lower mental component summary scores than those who received Ringer's acetate (median 45 (interquartile range 36-55) vs. 53 (39-60), p=0.01), with the differences mainly being in the scales Vitality and Mental Health. There was no difference in the physical component summary scores between groups, but patients in the HES group scored worse in Bodily Pain. Forty-nine percent of patients allocated to HES had experienced pruritus at any time after ICU discharge compared to 43% of those allocated to Ringer's (relative risk 1.13, 95% CI 0.83-1.55, p=0.43). Conclusion: In a subgroup of the 6S study, hydroxyethyl starch exposure was associated with worse self-perceived health-related quality of life than those assigned to Ringer's acetate, although there was no difference in the rate of pruritus.

Full Text:  Wittbrodt. Quality of life and pruritus in patients with severe sepsis resuscitated with hydroxyethyl starch. Long-term follow-up of a randomised trial. Critical Care 2013;17:R58


Nephrology Dialysis and Transplantation:     Acute Kidney Injury

Alves and co-workers evaluated the role of hypomagnesemia (serum magnesium concentration of <0.70 mmol/L) as a risk factor for the development of acute kidney injury (AKI) and non-recovery of renal function in 232 critically ill patients. There was no difference in the rate of hypomagnesemia between patients with or without AKI (47 and 62%, respectively, P = 0.36). The presence of hypomagnesemia was higher in patients who did not recover renal function when compared with patients who recovered renal function (70 versus 31%, P = 0.003). A multivariate analysis identified hypomagnesemia as an independent risk factor for non-recovery of renal function (P = 0.005). Patients with and without hypomagnesemia had similar mortality rates (P = 0.63). Conclusion: Hypomagnesemia was an independent risk factor for non-recovery of renal function in critically ill patients.

Abstract:  Alves. Hypomagnesemia as a risk factor for the non-recovery of the renal function in critically ill patients with acute kidney injury. Nephrol Dial Transplant 2013;28:910-916


Journal of the American College of Cardiology:     Natriuretic Peptides in Heart Failure

Van Veldhuisen and colleagues evaluated the prognostic value of B-type natriuretic peptide (BNP) in 615 patients with heart failure with either preserved ejection fraction (HFPEF), or  reduced left ventricular (LV) EF (≤40%). Patients had a mean age of 70 years, LVEF of 33% and were followed for 18 months. 257 patients (42%) met the primary endpoint, a composite of all-cause mortality and heart failure hospitalization, and 171 (28%) died. BNP levels were significantly higher in patients with reduced LVEF than in those with HFPEF (p < 0.001). BNP was a strong predictor of outcome, but LVEF was not. When similar levels of BNP were compared across the whole spectrum of LVEF, and for different cutoff levels of LVEF, the associated risk of adverse outcome was similar in HFPEF patients as in those with reduced LVEF. Conclusion: BNP levels are lower in patients with HFPEF than in patients with HF with reduced LVEF, but for a given BNP level, the prognosis in patients with HFPEF is as poor as in those with reduced LVEF.

Full Text:  Van Veldhuisen. B-Type Natriuretic Peptide and Prognosis in Heart Failure Patients With Preserved and Reduced Ejection Fraction. J Am Coll Cardiol 2013;61(14):1498-1506


Journal of the American Medical Association:     Chelation Therapy for Coronary Artery Disease

To investigate whether an EDTA-based chelation regimen, aimed at treating atherosclerosis, reduces cardiovascular events Lamas et al undertook a double-blind, placebo-controlled, 2 × 2 factorial randomized trial in 1708 patients aged 50 years or older who had experienced a myocardial infarction at least 6 weeks prior and had serum creatinine levels of 2.0 mg/dL or less. Patients were randomized to receive 40 infusions of a 500-mL chelation solution (3 g of disodium EDTA, 7 g of ascorbate, B vitamins, electrolytes, procaine, and heparin) (n=839) vs placebo (n=869) and an oral vitamin-mineral regimen vs an oral placebo. Infusions were administered weekly for 30 weeks, followed by 10 infusions 2 to 8 weeks apart. 17% of subjects withdrew consent because of adverse events. The primary end point, a composite of circulatory morbidity and mortality,  occurred in 222 (26%) of the chelation group and 261 (30%) of the placebo group (hazard ratio [HR], 0.82 [95% CI, 0.69-0.99]; P = .035). There was no effect on total mortality (chelation: 87 deaths [10%]; placebo, 93 deaths [11%]; HR, 0.93 [95% CI, 0.70-1.25]; P = .64), although the study was not powered for this comparison. The effect of EDTA chelation on the components of the primary end point other than death was of similar magnitude as its overall effect (MI: chelation, 6%; placebo, 8%; HR, 0.77 [95% CI, 0.54-1.11]; stroke: chelation, 1.2%; placebo, 1.5%; HR, 0.77 [95% CI, 0.34-1.76]; coronary revascularization: chelation, 15%; placebo, 18%; HR, 0.81 [95% CI, 0.64-1.02]; hospitalization for angina: chelation, 1.6%; placebo, 2.1%; HR, 0.72 [95% CI, 0.35-1.47]). Conclusion:  Among stable patients with a history of MI, use of an intravenous chelation regimen with disodium EDTA, compared with placebo, modestly reduced the risk of adverse cardiovascular outcomes, many of which were revascularization procedures.

Full Text: Lamas. Effect of Disodium EDTA Chelation Regimen on Cardiovascular Events in Patients With Previous Myocardial Infarction: The TACT Randomized Trial. JAMA 2013;309(12):1241-1250


Annals of Pharmacology:     Recombinant Activated Factor VII

Brophy and colleagues performed a retrospective case-control study to compare clinical outcomes and thromboembolic events in nonhemophiliac adult ICU patients who received rFVIIa (n=1459) versus ICU patients (n=1459) who did not. The most common primary diagnoses for patients receiving rFVIIa included traumatic brain injury, cirrhosis, and nontraumatic intracranial hemorrhage. Patients receiving rFVIIa were more likely to have comorbidities, including mechanical ventilation, acute kidney injury, sepsis, hemodialysis, and gastro intestinal bleeding (p < 0.0001). The average rFVIIa dose was 4.8 mg and 82% of patients received 1 dose. Compared to controls, patients receiving rFVIIa had greater odds of death (OR 2.1, 95% CI 1.8-2.6, p < 0.0001), transfusion (OR 2.1, 95% CI 1.8-2.5, p < 0.0001), and longer length of stay (p < 0.001). There was no significant difference in thromboembolic events between groups. Conclusion: In a retrospective study, precluding any examination of causality, the administration of rFVIIa was associated with worse clinical outcomes.

Abstract:  Brophy. Recombinant Activated Factor VII Use in Critically Ill Patients: Clinical Outcomes and Thromboembolic Events. Ann Pharmacother 2013;epublished March 27th



Circulation:     Atrial Fibrillation


Neurosurgery:     Spinal Injuries


Position Statement

Perioperative Medicine:     Peri-Operative Care of the Elderly



Intensive Care Medicine:     BEST TRIP Trial


Intensive Care Medicine:     Fluid Therapy


Intensive Care Medicine:     Resistant Bacteria


Journal of the American College of Cardiology:     Natriuretic Peptides in Heart Failure



Intensive Care Medicine:     Acute Kidney Injury


Trials:     FEAST Study


Journal of the American Medical Association:     Video Recording


Intensive Care Medicine:     Intensive Care Maestros


Journal of the American Medical Association:     Drug Development in Heart Failure


Review - Clinical


Brain Sciences:     Stem Cells for Stroke


Brain Sciences:     Ghrelin for Neuroprotection



Methodist Debakey Cardiovascular Journal:     Heart Failure


Methodist Debakey Cardiovascular Journal:     Peripartum Cardiomyopathy


Acute Medicine:    Acute Heart Failure


Circulation Journal:     Intrathoracic Impedence Monitoring


Indian Journal of Medical Research:     Stem Cells for Cardiac Regeneration


Swiss Medical Weekly:     Ventricular Assist Devices


Annals of Cardiac Surgery:     Antifibrinolytics in Cardiac Surgery


Journal of Geriatric Cardiology:     High-Sensitivity Cardiac Troponin


Journal of Geriatric Cardiology:     PCI in Nonagenarians


Journal of the American College of Cardiology:     Coronary Artery Interventions


Heart, Lung and Circulation:     Cardiac MRI


Cleveland Clinic Journal of Medicine:    Severe Aortic Stenosis



BMC Medicine:     Ventilator-Induced Lung Injury


Deutsches Ärzteblatt International:     Extracorporeal Gas Exchange


Annals of Thoracic Medicine:     Pulmonary Fibrosis


Indian Journal of Medical Research:     Chronic Obstructive Pulmonary Disease



Gastroenterology:     Top 100 Articles in Digestive Diseases



Current Opinion in Critical Care:     Liver Injury


Journal of Clinical & Experimental Hepatology:     Model for End-Stage Liver Disease


Journal of Clinical & Experimental Hepatology:     TB Drug-Induced Hepatotoxicity



Critical Care Research and Practice:     Acute Kidney Injury Epidemiology


Saudi Journal of Kidney Disease and Transplantation:     Acute Kidney Disease



Acute Medicine:    Acute Adrenal Failure


The Indian Journal of Endocrinology and Metabolism:     Anaesthesia for Thyroid Surgery


The Indian Journal of Endocrinology and Metabolism:     Anaesthesia for Parathyroid Surgery



Anaesthesiology Intensive Therapy:     Intraoperative Hypothermia



Current Reviews in Oncology Haematology:  Chemotherapy-Induced Cardiotoxicity


Journal of Antibiotics:     Major Classes of Antibiotics


Frontiers in Microbiology:     Antibiotics


Frontiers in Microbiology:     Carbapenemases


Cleveland Clinic Journal of Medicine:    Carbapenem-resistant Enterobacteriaceae


Current Opinion in Pulmonary Medicine:     Tuberculosis


Current Opinion in Pulmonary Medicine:     Respiratory Infections



Virulence:     Infectious Disasters



Annals of Medical Health Science Research:     Trauma Systems



New England Journal of Medicine:     Research during Emergency Responses


Diagnostics:     Diagnostics


Pharmaceutics:     Safety Monitoring in Research


Review - Basic Science

 Clinical Liver Disease:     Liver Anatomy


Clinical Liver Disease:     Liver Biopsy


Review - Non-Clinical

Annals of Medical Health Science Research:     Publishing



I hope you find these brief summaries and links useful.

Until next week