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Critical Care Reviews Newsletter

October 21st 2012





Welcome to the 46th 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.

Following the major studies from the ESICM meeting earlier this week, there are still a number of other newly published studies of interest. Yunos et al published an open-label study suggesting increased AKI and need for RRT with high chloride containing fluids; Vaara demonstrated an increased mortality in AKI patients with fluid overload requiring RRT than in similar patients without fluid overload; and Rhodes described the varying provision of critical care beds throughout Europe, varying from 23,890 in Germany to just a handful in Andora.

Both index cases in the respiratory coronavirus emergence and fungal meningitis outbreak have been described, and are presented along with associated commentaries.

The usual spread of review articles cover most organ systems and include refractory status epilepticus, spinal cord injury, LVADs, dopamine, airway management, liver coagulopathy, anticoagulants, AKI, crush syndrome and sepsis.

The topic for This Week's Papers is the third of a multi-part series on critical care controversies, starting with a paper questioning the use of etomidate in tomorrow's Paper of the Day

This week's CPD / CME  article and quiz are on decompensated cirrhosis. A personalised certificate of CPD activity can be saved and printed after successful completion of the activity.



Journal of the American Medical Association:     Acute Kidney Injury

To assess the association of a chloride-restrictive (vs chloride-liberal) intravenous fluid strategy with acute kidney injury in critically ill patients, Yunos et al performed a prospective, open-label study comparing 760 consecutively admitted ICU patients during a six month period with 773 patients consecutively admitted ICU patients during a subsequent six month period. The chloride rich solutions were  0.9% saline, 4% succinylated gelatin solution, or 4% albumin solution and chloride-poor solutions were Hartmann's solution, Plasma-Lyte 148, and chloride-poor 20% albumin. Comparing the initial chloride-rich to the subsequent chloride-poor period, chloride administration decreased from 694 to 496 mmol/patient. Similarly, the mean serum creatinine level increase was 22.6 μmol/L (95% CI, 17.5-27.7 μmol/L) vs 14.8 μmol/L (95% CI, 9.8-19.9 μmol/L) (P = .03), the incidence of injury and failure class of RIFLE-defined AKI was 14% (95% CI, 11%-16%; n = 105) vs 8.4% (95% CI, 6.4%-10%; n = 65) (P <.001), and the use of RRT was 10% (95% CI, 8.1%-12%; n = 78) vs 6.3% (95% CI, 4.6%-8.1%; n = 49) (P = .005). After adjustment for covariates, this association remained for incidence of injury and failure class of RIFLE-defined AKI (odds ratio, 0.52 [95% CI, 0.37-0.75]; P <.001) and use of RRT (odds ratio, 0.52 [95% CI, 0.33-0.81]; P = .004). There were no differences in hospital mortality, hospital or ICU length of stay, or need for RRT after hospital discharge.

Abstract: Yunos. Association Between a Chloride-Liberal vs Chloride-Restrictive Intravenous Fluid Administration Strategy and Kidney Injury in Critically Ill Adults. JAMA 2012;308(15):1566


Critical Care:     Acute Kidney Injury

To study the association between fluid accumulation at the initiation of renal replacement therapy, Vaara and colleagures conducted a prospective, multicenter, observational cohort study in 17 Finnish ICUs totaling 296 RRT-treated critically ill patients. Of 283 patients with complete data on fluid balance, 76 (26.9%) patients had fluid overload. The median (interquartile range) time from ICU admission to RRT initiation was 14 (3.3-41.5) hours. The 90-day mortality rate of the whole cohort was 116 of 296 (39.2%; 95% CI 38.6-39.8%). The crude 90-day mortality of patients with or without fluid overload was 45 of 76 (59.2%) vs. 65 of 207 (31.4%), P<0.001. In logistic regression, fluid overload was associated with an increased risk for 90-day mortality (odds ratio 2.6) after adjusting for disease severity, time of RRT initiation, initial RRT modality, and sepsis. Of the 168 survivors with data on RRT use at 90 days, 34 (18.9%, 95% CI 13.2-24.6%) were still dependent on RRT.

Abstract:  Vaara. Fluid overload is associated with an increased risk for 90-day mortality in critically ill patients with renal replacement therapy: data from the prospective FINNAKI study. Critical Care 2012;16:R197


Intensive Care Medicine:     European Critical Care Provision

Rhodes et al performed a prospective data collection of critical care bed numbers in European countries (July 2010 to July 2011). There were 2,068,892 acute care hospital beds in Europe, with an average of 409 acute care beds per 100,000 head of population. There were 73,585 critical care beds in Europe, with an average of 11.5 beds per 100,000 head of population for Europe as a whole, but with wide inter-country differences. Selected data are highlighted below. The numbers of critical care beds per country corrected for population size were positively correlated with GDP (r2 = 0.16, p = 0.05), numbers of acute care beds corrected for population (r2 = 0.12, p = 0.05) and the percentage of acute care beds designated as critical care (r2 = 0.59, p < 0.0001). They were not correlated with the proportion of GDP expended on healthcare.

Abstract: Rhodes. The variability of critical care bed numbers in Europe. Intensive Care Med 2012;38:1647–1653

european critical care 211012

Intensive Care Medicine:     Surviving Sepsis Campaign

Using a surviving sepsis database of 27,836 subjects from 218 sites, Caserely et al investigated the effect of low-dose steroids in adult septic shock. Of the total cohort 17,847 were eligible to receive low-dose steroids, with 8,992 patients (50.4 %) receiving this therapy. Patients in Europe (59.4 %) and South America (51.9 %) were more likely to be prescribed low-dose steroids compared to their counterparts in North America (46.2 %, p < 0.001). The adjusted hospital mortality was significantly higher (OR 1.18, 95 % CI 1.09–1.23, p < 0.001) in patients who received low-dose steroids compared to those who did not. There was still an association with increased adjusted hospital mortality with low-dose steroids even if they were prescribed within 8 h (OR 1.23, 95 % CI 1.13–1.34, p < 0.001).

Abstract:  Casserly. Low-dose steroids in adult septic shock: results of the Surviving Sepsis Campaign. Intensive Care Medicine 2012; epublished ahead of print


Critical Care Medicine:     Etomidate

Chan et al performed a systematic review and meta analysis of randomized controlled and observational studies including septic patients to assess the effects of etomidate on adrenal insufficiency and all-cause mortality. Subjects who received etomidate (studies 5, subjects 865) were more likely to die (pooled relative risk 1.20; 95% CI 1.02–1.42; Q statistic, 4.20; I2 statistic, 4.9%). Etomidate administration (studies 7, subjects 1,303)also increased the likelihood of developing adrenal insufficiency (pooled relative risk 1.33; 95% CI 1.22–1.46; Q statistic, 10.7; I2 statistic, 43.9%).

Abstract: Chan. Etomidate is associated with mortality and adrenal insufficiency in sepsis: A meta-analysis. Crit Care Med 2012;40(11):2945–2953


Critical Care:     Subarachnoid Haemorrhage

Ma et al performed a systematic review and meta-analysis of published randomized controlled trials (n=5) to determine the efficacy of endothelin-receptor antagonists (ETRAs) in patients (n=2,595) with aneurysmal subarachnoid haemorrhage. The pooled relative risk of mortality and unfavorable outcome after SAH were 1.03 (95% CI: 0.77 to 1.36) and 1.07 (95% CI: 0.93 to 1.22) respectively. The pooled RR for delayed cerebral infarction was 0.87 (95% CI: 0.74 to 1.03), for delayed ischaemic neurological deficit 0.77 (95% CI: 0.66 to 0.90), and for angiographic vasospasm 0.66 (95% CI: 0.57 to 0.77). There were significant increase in lung complications (RR 1.80, 95% CI: 1.55 to 2.09), hypotension (RR 2.42, 95% CI: 1.78 to 3.29) and anaemia (RR 1.47, 95% CI: 1.19 to 1.83) in patients receiving ETRAs.

Abstract:  Ma. Endothelin-receptor antagonists for aneurysmal subarachnoid hemorrhage: an updated meta-analysis of randomized controlled trials. Critical Care 2012;6:R198


Intensive Care Medicine:     Percutaneous Extracorporeal Lung Assist

Kluge et al undertook a multicentre, retrospective study to assess whether percutaneous extracorporeal lung assist (PECLA, n=21) could prvide an effective and safe alternative to invasive mechanical ventilation (n=21, match controls) in patients with chronic pulmonary disease and acute hypercapnic ventilatory failure not responding to noninvasive ventilation. Of the 21 patients treated with PECLA, 19 (90 %) did not require intubation. Median PaCO2 levels and pH in arterial blood prior to PECLA were 84.0 mmHg (54.2–131.0) and 7.28 (7.10–7.41), respectively and within 24hours had improved to   52.1 (33.0–70.1; p < 0.001) and 7.44 (7.27–7.56; p < 0.001), respectively. Two major and seven minor bleeding complications, plus one pseudoaneurysm and one heparin-induced thrombocytopenia type 2 occured related to the device. Compared to the matched control group, there was a trend toward a shorter hospital length of stay in the PECLA group (adjusted p = 0.056). There was no group difference in the 28-day (24 % vs. 19 %, adjusted p = 0.845) or 6-month mortality (33 % vs. 33 %).

Abstract:  Kluge. Avoiding invasive mechanical ventilation by extracorporeal carbon dioxide removal in patients failing noninvasive ventilation. Intensive Care Med 2012;38(10):1632-1639


Clinical Infectious Disease:     Antibacterial Infusions

Abstract:  Dulhunty and colleagues undertook a prospective, double-blind, randomized controlled trial to compare the clinical and pharmacokinetic differences between continuous (n=30) and intermittent (n=30) dosing of piperacillin-tazobactam, meropenem and ticarcillin-clavulanate in patients with severe sepsis. Plasma antibiotic concentrations exceeded the minimum inhibitory concentration in 82% of patients (18/22) in the continuous arm versus 29% (6/21) in the intermittent arm (P = 0.001). Clinical cure was higher in the continuous group (70% vs. 43%; P = 0.037), but neither ICU-free days (19.5 vs. 17 days; P = 0.14), nor survival to hospital discharge (90% vs 80%; P = 0.47) differed between groups.

Abstract:  Dulhunty. Continuous infusion of beta-lactam antibiotics in severe sepsis: a multicenter double-blind, randomized controlled trial. Clin Infect Dis 2012; epublished ahead of print


Thorax:     Community-Acquired Pneumonia

Rodrigo et al compared β-lactam/macrolide combination therapy with β-lactam monotherapy udied studied 5240 adults hospitalised with community-acquired pneumonia to . The overall 30-day inpatient death rate was 24.4%. Combination therapy was prescribed in 3239 (61.8%) patients. In a multivariable model, combination therapy was significantly associated with lower 30-day inpatient death rate in patients with moderate-severity CAP (adjusted OR 0.54, 95% CI 0.41 to 0.72) and high-severity CAP (adjusted OR 0.76, 95% CI 0.60 to 0.96) but not low-severity CAP.

Abstract:  Rodrigo. Single versus combination antibiotic therapy in adults hospitalised with community acquired pneumonia. Thorax 2012; epublished ahead of print.


Archives of Surgery:     Blood Transfusion

Holcomb et al undertook a prospective cohort study in 10 American level 1 trauma centres to relate in-hospital mortality to early transfusion of plasma and/or platelets and to time-varying plasma:RBC and platelet:RBC ratios. The study recruited adult trauma patients surviving for 30 minutes after admission who received a transfusion of at least 1 unit of RBCs within 6 hours of admission (n = 1245, the original study group) and at least 3 total units (of RBCs, plasma, or platelets) within 24 hours (n = 905, the analysis group). Increased ratios of plasma:RBCs (adjusted hazard ratio = 0.31; 95% CI, 0.16-0.58) and platelets:RBCs (adjusted hazard ratio = 0.55; 95% CI, 0.31-0.98) were independently associated with decreased 6-hour mortality, when hemorrhagic death predominated. In the first 6 hours, patients with ratios less than 1:2 were 3 to 4 times more likely to die than patients with ratios of 1:1 or higher. After 24 hours, plasma and platelet ratios were unassociated with mortality, when competing risks from nonhemorrhagic causes prevailed.

Abstract:  Holcomb. The Prospective, Observational, Multicenter, Major Trauma Transfusion (PROMMTT) Study. Comparative Effectiveness of a Time-Varying Treatment With Competing Risks. Arch Surg 2012;():1-10


Trials:     STUDY PROTOCOL - Traumatic Brain Injury

Gregson et al are to perform an international multicenter pragmatic randomized controlled trial in 840 patients investigating whether a policy of early surgery improves outcome compared to initial conservative treatment in patients with traumatic intracerebral haemorrhage. Eligibility criteria are: within 48 h of injury; evidence of TICH on CT scan with a confluent volume of attenuation significantly raised above that of the background white and grey matter that has a total volume >10 mL; and the treating neurosurgeon is in equipoise. Exclusion criteria are: a significant surface hematoma (EDH or SDH) requiring surgery; a hemorrhage/contusion located in the cerebellum; three or more separate hematomas fulfilling inclusion criteria; or severe pre-existing physical or mental disability or severe co-morbidity which would lead to poor outcome even if the patient made a full recovery from the head injury. Patients randomized to surgery will receive surgery within 12 h. All patients have a CT scan at 5 days (+/-2 days) to assess changes in hematoma size. Follow-up is by postal questionnaire at 6 and 12 months.

Full Text:  Gregson. Surgical trial in traumatic intracerebral hemorrhage (STITCH(Trauma)): study protocol for a randomized controlled trial. Trials 2012;13:193


Trials:     STUDY PROTOCOL - Enteral Feeding

Arabi and colleagues aim to compare permissive enteral underfeeding with enteral target feeding in 862 critically ill medical- surgical adult patients in an international multi-center randomized controlled trial.  Patients in the permissive group receive 50% (40% to 60%) of the calculated caloric requirement, while those in the targeted group receive 100% (70% to 100%). The primary outcome is 90-day all-cause mortality. Secondary outcomes include ICU and hospital mortality, 28-day, and 180-day mortality as well as health care-associated infections, organ failure, and length of stay in the ICU and hospital. The trial has 80% power to detect an 8% absolute reduction in 90-day mortality assuming a baseline risk of death of 25% at an alpha level of 0.05. This study is currently recruiting and aims to complete by November 2013.

Full Text:  Arabi. Permissive underfeeding versus target enteral feeding in adult critically ill patients (PermiT Trial): a study protocol of a multicenter randomized controlled trial. Trials 2012;13:191


Case History

Novel Coronavirus

New England Journal of Medicine:    

Editorial: Anderson. Emerging Human Coronaviruses — Disease Potential and Preparedness. NEJM 2012; epublished October 17th


Fungal Meningitis Outbreak

New England Journal of Medicine:    

Preliminary Report: Kauffman. Fungal Infections Associated with Contaminated Methylprednisolone Injections — Preliminary Report. NEJM 2012; epublished Oct 19th


Annals of Internal Medicine:    


Review - Clinical

Lancet Neurology:     Epilepsy

Journal of Emergencies, Trauma and Shock:     Airway Management


Journal of Emergencies, Trauma and Shock:     Haemorrhagic Shock


Gastroenterology Research and Practice:     Biotics


Current Opinion in Critical Care:      Sepsis


African Journal of Emergency Medicine:     Crush Syndrome


Blood Transfusion:     Liver Coagulopathy


Industrial Psychiatry Journal:     Influenza


Current Gastroenterology Reports:     Glycaemic Control


Clinics (Sao Paulo):     Spinal Cord Injury


Digestive Surgery:     Gastric Neuroendocrine Tumours


Swiss Medical Weekly:     Left Ventricular Assist Device    


Nephrology Dialysis Transplantation:     Peritoneal Dialysis


Indian Journal of Urology:     Acute Kidney Injury


Translational Medicine @ UniSa:    Dopamine


Review - Basic Science

Journal of Hematology & Oncology


Review - Non-Clinical

Academic Emergency Medicine:     Literature Review


Medical Law Review:     Research Consent



I hope you find these brief summaries and links useful.

Until next week