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Critical Care Reviews Newsletter

January 20th 2013



Welcome to the 59th 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 numerous research studies include papers suggesting a lack of utility of monitoring gastric residual volumes; in the hands of pre-hospital personnell, possible harm from advanced airway management in out-of-hospital cardiac arrest; and in sepsis, possible benefit from the use of combination antimicrobial therapy, using agents with different mechanisms of action.

This week's guidelines are from the American College of Emergency Physicians and the American College of Cardiology Foundation, and include guidance on the management of stoke and generating guidelines. There are editorials on nutrition in ICU and the use of adrenaline in resuscitation.

Amongst the clinical review articles are papers on therapeutic hypothermia post cardiac arrest, acute aortic syndromes, pulmonary embolism, drug-induced liver injury, cardiorenal syndrome, age of transfused red cells, influenza and magnesium in obstetrics. The basic science papers include reviews on apoptosis and proteomics.

The topic for This Week's Papers is fluid balance, starting with a paper on fluid overload in critically ill patients with acute kidney injury in tomorrow's Paper of the Day.



Journal of the American Medical Association:     Gastric Feeding

To test the hypothesis that the risk of ventilator-associated pneumonia is not increased when residual gastric volume is not monitored compared with routine residual gastric volume monitoring Reignier and colleagues performed a randomized, noninferiority, open-label, multicenter trial in 9 French (ICUs) recruiting 452 adults requiring invasive mechanical ventilation for more than 2 days and given enteral nutrition within 36 hours after intubation. There was no difference in the incidence of VAP (interventional group: 38/227; 16.7%) versus control group (35/222 patients; 15.8%)  (difference: 0.9%; 90% CI: −4.8% to 6.7%). Similarly, there were no significant differences in other ICU-acquired infections, mechanical ventilation duration, ICU stay length, or mortality rates. The proportion of patients receiving 100% of their calorie goal was higher in the intervention group (odds ratio, 1.77; 90% CI, 1.25-2.51; P = .008). Conclusion: In critically ill mechanically ventilated patients receiving early nasogastric feeding, the absence of gastric volume monitoring was not inferior to routine residual gastric volume monitoring in terms of multiple outcomes, including the incidence of VAP.

Abstract:  Reignier. Effect of Not Monitoring Residual Gastric Volume on Risk of Ventilator-Associated Pneumonia in Adults Receiving Mechanical Ventilation and Early Enteral Feeding:  A Randomized Controlled Trial. JAMA 2013;309(3):249


Journal of the American Medical Association:     Out-of-Hospital Cardiac Arrest

To determine whether prehospital advanced airway management is associated with favorable outcome after adult out-of-hospital cardiac arrest, Hasegawa et al performed a prospective, nationwide, population-based study on the All-Japan Utstein Registry, involving 649 654 consecutive adult patients who had an OHCA and in whom resuscitation was attempted by emergency responders with subsequent transport to medical institutions. 367 837 (57%) underwent bag-valve-mask ventilation and 281 522 (43%) advanced airway management, including 41 972 (6%) with endotracheal intubation and 239 550 (37%) with use of supraglottic airways. Advanced airway management was associated with a lower rate of favorable neurological outcome compared with the bag-valve-mask group (1.1% vs 2.9%; OR: 0.38; 95% CI: 0.36-0.39). In a propensity score–matched cohort (357 228 patients), the adjusted odds of neurologically favorable survival were significantly lower both for endotracheal intubation (adjusted OR, 0.45; 95% CI, 0.37-0.55) and for use of supraglottic airways (adjusted OR, 0.36; 95% CI, 0.33-0.39). Conclusion: In a prospective registry study, in out-of-hospital cardiac arrest, in comparison with bag-valve-mask ventilation, both endotracheal intubation and supraglottic airway use were associated with decreased odds of neurologically favorable survival.

Abstract:  Hasegawa. Association of Prehospital Advanced Airway Management With Neurologic Outcome and Survival in Patients With Out-of-Hospital Cardiac Arrest. JAMA 2013;309(3):257


Critical Care:     Anti-Microbial Therapy

Díaz-Martín performed a national multicenter study  to investigate the impact of combination antimicrobial therapy within the first 6 hours of the diagnosis of severe sepsis or septic shock, including antimicrobials with different mechanisms of action (different-class combination therapy, DCCT), on mortality. 1,372 patients were enrolled, 1,022 (74.5%) with community-acquired sepsis and 350 (25.5%) with nosocomial sepsis. The most frequently prescribed antibiotic agents were β-lactams (902, 65.7%) and carbapenems (345, 25.1%). DCCT was administered to 388 patients (28.3%), and non-DCCT was administered to 984 (71.7%). DCCTs was associated with a lower mortality than non-DCCTs (34% vs 40%; P = 0.042). 

Full TextDíaz-Martín. Antibiotic prescription patterns in the empiric therapy of severe sepsis: combination of antimicrobials with different mechanisms of action reduces mortality Critical Care 2012;16:R223


Clinical Nutrition:     Effect of Feeding on Pneumonia

Jiyong and colleagues performed a systematic review and meta analysis comparing gastric with post-pyloric feeding on the incidence of pneumonia. 15 randomized clinical trials with 966 patients were included. Post-pyloric feeding was associated with reduction in pneumonia compared with gastric feeding (RR 0.63, 95% CI 0.48–0.83, p = 0.001; I2 = 0%). The risk of aspiration (RR: 1.11; 95% CI: 0.80–1.53, p = 0.55; I2 = 0%) and vomiting (RR, 0.80; 95% CI, 0.38–1.67, p = 0.56; I2 = 65.3%) were not significantly different between patients treated with gastric and post-pyloric feeding. Conclusion:  In critically ill patients, post-pyloric feeding, in comparison with gastric feeding, was associated with a reduced incidence of pneumonia

Full Text:  Jiyong. Effect of gastric versus post-pyloric feeding on the incidence of pneumonia in critically ill patients: Observations from traditional and Bayesian random-effects meta-analysis. Clinical Nutrition 2013;32(1):8-15


New England Journal of Medicine:     Clostridium Difficile Diarrhoea

Van Nood and colleagues completed an open-label, randomized, controlled trial in 42 patients with resistant C. difficile infection, comparing (1) an initial vancomycin regimen (500 mg orally four times per day for 4 days), followed by bowel lavage and subsequent infusion of a solution of donor faeces through a nasoduodenal tube (n=16); (2) a standard vancomycin regimen (500 mg orally four times per day for 14 days)(n=13); or (3) a standard vancomycin regimen with bowel lavage (n=13). The study was stopped after an interim analysis due a superior result with the first preparation, with 13 (81%) having resolution of C. difficile–associated diarrhoea after the first infusion. The 3 remaining patients received a second infusion with faeces from a different donor, with 2 patients being successfully treated. Resolution of C. difficile infection occurred in 4 of 13 patients (31%) receiving vancomycin alone and in 3 of 13 patients (23%) receiving vancomycin with bowel lavage (P<0.001 for both comparisons with the infusion group). No significant differences in adverse events among the three study groups were observed except for mild diarrhoea and abdominal cramping in the infusion group on the infusion day. Conclusion: Faecal transplantation following oral vancomycin therapy and bowel lavage was superior to either oral vancomycin and bowel lavage or oral vancomycin alone with respect to resolution of resistant C. difficile diarrhoea at 10 weeks post treatment.

Full Text:  Van Nood. Duodenal Infusion of Donor Feces for Recurrent Clostridium difficile. N Eng J Med 2013

Associated Editorial:  Kelly. Fecal Microbiota Transplantation — An Old Therapy Comes of Age. N Eng J Med 2013


Acta Anaesthesiologica Scandinavica:     Inotropic Support in Septic Shock

Wilkman et al performed a retrospective analysis of 420 subjects with septic shock, using both logistic regression and propensity scoring to analyse the association of inotrope treatment with 90-day mortality. One hundred eighty-six (44.3%) patients received inotrope treatment during the first 24 h in ICU. Of those, 168 (90.3%) received dobutamine, 29 (15.6%) levosimendan, and 23 (12.4%) epinephrine. Blood lactate (P < 0.001), central venous pressure, (P < 0.001), and norepinephrine dose (P  = 0.03) were independently associated with inotrope treatment. Patients with inotrope treatment had a higher 90-day mortality (42.5% vs. 23.9%, P < 0.001). Age (P < 0.001), APACHE II score (P < 0.001), and inotrope treatment (P = 0.003) were independently associated with 90-day mortality also after adjustment with propensity score. Conclusion: In this retrospective review, the use of inotrope treatment in septic shock was associated with increased 90-day mortality without and after adjustment with propensity to receive inotrope.

BMJ Open:     Refeeding Syndrome

Rio and colleagues undertook a single-centre prospective cohort study in 243 adults to determine the occurrence of refeeding syndrome in adults commenced on artificial nutrition support. 133 participants had one or more risk factors of body mass index <16-18.5≥(kg/m(2)), unintentional weight loss >15% in the preceding 3-6 months, very little or no nutritional intake >10 days, history of alcohol or drug abuse and low baseline levels of serum potassium, phosphate or magnesium prior to recruitment. Poor nutritional intake for more than 10 days, weight loss >15% prior to recruitment and low-serum magnesium level at baseline predicted the refeeding syndrome with a sensitivity of 66.7%: specificity was >80% apart from weight loss of >15% which was 59.1%. Baseline low-serum magnesium was an independent predictor of the refeeding syndrome (p=0.021). Three participants (2% 3/243) developed severe electrolyte shifts, acute circulatory fluid overload and disturbance to organ function following artificial nutrition support and were diagnosed with refeeding syndrome. There were no deaths attributable to the refeeding syndrome. Conclusion: Refeeding syndrome was a rare, survivable phenomenon that occurred during hypocaloric nutrition support in at risk subjects. 

Full Text:  Rio. Occurrence of refeeding syndrome in adults started on artificial nutrition support: prospective cohort study. BMJ Open 2013;3(1)


Thorax:     Idiopathic Pulmonary Fibrosis

Shulgina and colleagues undertook a double-blind multicentre study in 181 patients with fibrotic idiopathic interstitial pneumonia comparing co-trimoxazole 960 mg twice daily with placebo for 12 months in addition to usual care. Co-trimoxazole had no effect on FVC (mean difference 15.5 ml (95% CI −93.6 to 124.6)), Dlco (mean difference −0.12 mmol/min/kPa (95% CI 0.41 to 0.17)), 6 minute walk test or MRC dyspnoea score (intention-to-treat analysis). The findings of the per-protocol analysis were the same except that co-trimoxazole treatment resulted in a significant improvement in EQ5D-based utility (mean difference 0.12 (95% CI 0.01 to 0.22)), a reduction in the percentage of patients requiring an increase in oxygen therapy (OR 0.05 (95% CI 0.00 to 0.61)) and a significant reduction in all-cause mortality (co-trimoxazole 3/53, placebo 14/65, HR 0.21 (95% CI 0.06 to 0.78), p=0.02)) compared with placebo. The use of co-trimoxazole reduced respiratory tract infections but increased the incidence of nausea and rash. Conclusions The addition of co-trimoxazole therapy to standard treatment for fibrotic idiopathic interstitial pneumonia had no effect on lung function but resulted in improved quality of life and a reduction in mortality in those adhering to treatment.

Abstract:  Shulgina. Treating idiopathic pulmonary fibrosis with the addition of co-trimoxazole: a randomised controlled trial. Thorax 2013;68:155-162


Emergency Medicine Australasia:     Predicting Outcome Using Laboratory Tests

Loekito et al performed an initial retrospective observational study, investigating 160 341 batches of laboratory tests in 71 453 emergency department patients for a total of 1 million individual measurements,  to predict imminent MET calls, ICU admission or death. They then externally validated their findings in 37 367 batches from a cohort of 21 430 ED patients in a seperate hospital. In the inception cohort there were 341 MET calls, 160 ICU admissions from the wards and 858 deaths. Multivariable modelling achieved a receiver operating characteristic area under the curve (ROC-AUC) of 0.69 (95% CI 0.63–0.74) for imminent MET call with prediction occurring a mean of 11.9 h before the call, a ROC-AUC of 0.82 (95% CI 0.73–0.87) for imminent ICU admission and a ROC-AUC of 0.90 (95% CI 0.87–0.91) for imminent death. In the validation cohort the multivariate model achieved a ROC-AUC of 0.70 (95% CI 0.66–0.73) for imminent MET call, a ROC-AUC of 0.84 (95% CI 0.78–0.90) for imminent ICU admission and a ROC-AUC of 0.89 (95% CI 0.86–0.91) for imminent death. Conclusion: Commonly performed laboratory tests can help predict imminent MET calls, ICU admission or death in ED patients.

Abstract:  Loekito. Common laboratory tests predict imminent medical emergency team calls, intensive care unit admission or death in emergency department patients. Emergency Medicine Australasia 2013; epublished January 8th


Journal of Anesthesia:     Immunoglobulin Therapy in Sepsis

Toth et al perfomed a prospective randomised controlled pilot study  investigating the effects of IgM-enriched immunoglobulin treatment (5 ml/kg predicted body weight for 3 days) in 33 patients with early septic shock accompanied by severe respiratory failure. There was no effect on daily multi-organ dysfunction scores over 8 days, length of ICU stay, mechanical ventilation, or vasopressor support during the ICU stay or in 28-day mortality.  Conclusion: In this smal pilot study the use of IgM-enriched immunoglobulin preparation did not improve organ dysfunction as compared to standard sepsis therapy.

Abstract:  Toth. Effects of IgM-Enriched Immunoglobulin Therapy in Septic-Shock–Induced Multiple Organ Failure: Pilot Study. Journal of Anaesthesia 2013;epublished



Annals of Emergency Medicine:     Stroke Thrombolysis


Circulation:     Guideline Methodology



Journal of Enteral and Parenteral Nutrition:     Nutrient Provision in ICU


European Journal of Anaesthesiology:     Adrenaline for Resuscitation



Circulation: Heart Failure


Review - Clinical


Circulation:     Therapeutic Hypothermia post Cardaic Arrest

Neurosurgery:     Mechanical Clot Retrieval in Stroke



Hospital Chronicles:     Acute Aortic Syndromes



Archives of Medical Science:     Pulmonary Embolism


Interactive CardioVasc Thoracic Surgery:     Pneumothorax


Therapeutics and Clinical Risk Management:     Miliary Tuberculosis


Arch Bronconeumology:     MicroRNAs in Lung Disease



Journal of Clinical Medical Research:     Enteral Nutrition


North American Journal of Medical Science:     Nasogastric Tube Insertion



Current Biomarker Findings:     Drug-Induced Liver Injury



Hospital Chronicles:     Cardiorenal Syndrome



Annals of Intensive Care:     Age of Transfused Red Cells


Clinical Therapeutics: Rivaroxaban



Journal of the American Medical Association:     Bacterial Coinfection in Influenza


Journal of the American Medical Association:     Influenza Vaccination


Acta Anaesthesiologica Taiwanica:     Ketamine-induced Imunosuppression


Archives of Medical Science:     Lyme Disease



International Journal of Obstetric Anaesthesia:     Magnesium



Clinical and Developmental Immunology:     Complement in Multiorgan Failure

Lung India:     Fat Embolim Syndrome


Journal of Orofacial Science:     Tumour Markers


Current Cardiology Reports:     Magnetic Resonance Coronary Angiography

Review - Basic Science

Journal of Orofacial Science:     Apoptosis


Cardiovascular Research:     Proteomics


I hope you find these brief summaries and links useful.

Until next week