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Critical Care Reviews Newsletter

February 10th 2013



Welcome to the 62nd 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 are dominated by publications from the New England Journal of Medicine, with three articles on stroke plus a further two on infection control and venothromboembolism prophylaxis. A further article from Stroke investigates the effects of blood pressure reduction in acute haemorhagic stroke, while two systematic reviews from the British Journal of Anaesthesia investigate the efficacy of early therapeutic hypothermia in traumatic brain injury and critical care for patients with endstage renal failure.

The Cochrane Collaboration have issued three new reviews on the use of high volume haemofiltration in severe sepsis, thyroid hormone in acute kidney injury and tranexamic acid in emergency and urgent surgery.

This week's guidelines are on acute stroke management, post-anaesthetic management and publication standards. There are editorials on multi-resistant bacteria, death under anaesthesia, and for the skeptics, an interesting paper on medical reversal from Emergency Medicine Australasia. The ongoing development of social media in critical care is addressed in a commentary from EM News.

Once again the clinical review articles cover a wide range of topics, including an entire free book on therapeutic hypothermia, and with an increasing number of paediatric intensivists now using the site, there are a couple of articles for those caring for the youngest patients.

The topic for This Week's Papers is antibacterial drugs, starting with a paper on carbapenams in tomorrow's Paper of the Day.



Lancet Infectious Disease:     Procalcitonin as a Sepsis Biomarker

Wacker and colleagues performed a systematic review and meta analysis, including 30 studies and 3244 patients, to assess the accuracy and clinical value of procalcitonin for diagnosing sepsis in critically ill patients. Procalcitonin had a mean sensitivity of 0·77 (95% CI 0·72—0·81) and specificity of 0·79 (95% CI 0·74—0·84), with an AUC of 0·85 (95% CI 0·81—0·88) for identifying sepsis. There was substantial heterogeneity (I2=96%, 95% CI 94—99) between the studies, with none of population, admission category, assay used, severity of disease, or description and masking of the reference standard, accounting for this difference. Conclusion: Procalcitonin has good ability to identify sepsis in the critically ill, although the results of the test must be interpreted carefully in the context of medical history, physical examination, and microbiological assessment.

Abstract: Wacker. Procalcitonin as a diagnostic marker for sepsis: a systematic review and meta-analysis. The Lancet Infectious Diseases 2013;epublished February 1st


New England Journal of Medicine:     Stroke

In patients with moderate-to-severe acute ischemic stroke who received intravenous t-PA within 3 hours after symptom onset, Broderick et al randomly assigned eligible patients to receive additional endovascular therapy or not, in a 2:1 ratio. The study was stopped early because of futility after 656 participants had undergone randomization. The proportion of participants with a modified Rankin score of 2 or less (indicating functional independence) at 90 days did not differ significantly according to treatment (40.8% with endovascular therapy and 38.7% with intravenous t-PA alone; absolute adjusted difference, 1.5 % points; 95% CI 6.1 to 9.1). Mortality was unchanged at 90 days ( endovascular-therapy: 19.1% versus intravenous t-PA 21.6%; P=0.52), as was the proportion of patients with symptomatic intracerebral hemorrhage within 30 hours after initiation of t-PA (6.2% and 5.9%, respectively; P=0.83). Also, there were there no significant differences for the predefined subgroups of patients with an NIHSS score of >20 or <20. Conclusion: Additional endovascular therapy after intravenous t-PA was not associated with improved outcomes in acute ischaemic stroke.

Full Text:  Broderick. Endovascular Therapy after Intravenous t-PA versus t-PA Alone for Stroke (IMS III trial). N Eng J Med 2013;epublished February 7th


Ciccone et al performed a controlled trial in 362 patients with acute ischemic stroke, randomized within 4.5 hours after onset to endovascular therapy (intraarterial thrombolysis with recombinant tissue plasminogen activator [t-PA], mechanical clot disruption or retrieval, or a combination of these approaches, n=181) or intravenous t-PA (n=181). The median time from stroke onset to the start of treatment was shorter for endovascular therapy than for intravenous t-PA (3.75 hours versus 2.75 hours, P<0.001). At 3 months, 55 patients in the endovascular-therapy group (30.4%) and 63 in the intravenous t-PA group (34.8%) were alive without disability (odds ratio adjusted for age, sex, stroke severity, and atrial fibrillation status at baseline, 0.71; 95% CI 0.44 to 1.14; P=0.16). There were no differences in fatal or nonfatal symptomatic intracranial hemorrhage within 7 days (6% each group), or in rates of other serious adverse events or the case fatality rate. Conclusion: in patients with acute ischemic stroke endovascular therapy is not superior to standard treatment with intravenous t-PA.

Full Text: Ciccone. Endovascular Treatment for Acute Ischemic Stroke (SYNTHESIS Expansion trial). N Eng J Med 2013;epublished February 6th


Kidwell and colleagues completed a randomized controlled trial in 118 patients within 8 hours after the onset of large-vessel, anterior-circulation strokes comparing mechanical embolectomy (Merci Retriever or Penumbra System) or receive standard care. Revascularization in the embolectomy group was achieved in 67% of the patients. Ninety-day mortality was 21%, and the rate of symptomatic intracranial hemorrhage was 4%; neither rate differed across groups. Among all patients, mean scores on the modified Rankin scale did not differ between embolectomy and standard care (3.9 vs. 3.9, P=0.99). Embolectomy was not superior to standard care in patients with either a favorable penumbral pattern (mean score, 3.9 vs. 3.4; P=0.23) or a nonpenumbral pattern (mean score, 4.0 vs. 4.4; P=0.32). In the primary analysis of scores on the 90-day modified Rankin scale, there was no interaction between the pretreatment imaging pattern and treatment assignment (P=0.14). Conclusion: A favorable penumbral pattern on neuroimaging did not identify patients who would differentially benefit from endovascular therapy for acute ischemic stroke, nor was embolectomy shown to be superior to standard care.

Full Text:  Kidwell. A Trial of Imaging Selection and Endovascular Treatment for Ischemic Stroke (MR RESCUE study). N Eng J Med 2013;epublished February 8th


New England Journal of Medicine:     Rivaroxaban

To determine the appropriate duration of thromboprophylaxis in hospitalized patients with acute medical illnesses, Cohen et al completed a multicenter, randomized, double-blind trial in 8101 patients, comparing, (I think, it's remarkably poorly described) (1) early enoxaparin with early rivaroxaban, and (2) follow-on oral placebo in those who received enoxaparin versus extended duration rivaroxaban. Venous thromboembolism occurred in 78 of 2938 patients (2.7%) receiving rivaroxaban and 82 of 2993 patients (2.7%) receiving enoxaparin at day 10 (relative risk with rivaroxaban, 0.97; 95% CI 0.71 to 1.31; P=0.003 for noninferiority) and in 131 of 2967 patients (4.4%) who received rivaroxaban and 175 of 3057 patients (5.7%) who received enoxaparin followed by placebo at day 35 (relative risk, 0.77; 95% CI, 0.62 to 0.96; P=0.02). A principal safety outcome event occurred in 111 of 3997 patients (2.8%) in the rivaroxaban group and 49 of 4001 patients (1.2%) in the enoxaparin group at day 10 (P<0.001) and in 164 patients (4.1%) and 67 patients (1.7%) in the respective groups at day 35 (P<0.001). Conclusion: In acutely ill medical patients, rivaroxaban was (1) noninferior to enoxaparin for standard-duration thromboprophylaxis; (2) extended-duration rivaroxaban reduced the risk of venous thromboembolism, although (3) rivaroxaban was associated with an increased risk of bleeding.

Abstract:  Cohen. Rivaroxaban for Thromboprophylaxis in Acutely Ill Medical Patients (MAGELLAN study). N Engl J Med 2013; 368:513-523


New England Journal of Medicine:     Chlorhexidine for Infection Prevention

Climo and colleagues performed a multicenter, cluster-randomized, nonblinded crossover trial in 7727 patients, comparing daily bathing with 2% chlorhexidine-impregnated washcloths with non-antimicrobial washcloths on the acquisition of multidrug-resistant organisms and the incidence of hospital-acquired bloodstream infections. The overall rate of multidrug-resistant organisms acquisition was 23% lower rate with chlorhexidine bathing (5.10 cases per 1000 patient-days versus 6.60 cases per 1000 patient-days; P=0.03). Similarly, the overall rate of hospital-acquired bloodstream infections was 28% lower rate with chlorhexidine-impregnated washcloths (4.78 cases per 1000 patient-days versus 6.60 cases per 1000 patient-days, P=0.007). No serious skin reactions were noted. Conclusion: Compared with standard non-antimicrobial washing, washing with 2% chlorhexidine was associated with lower rates of acquisition of multidrug-resistant organisms and lower incidence of hospital-acquired bloodstream infections.

Abstract:  Climo. Effect of Daily Chlorhexidine Bathing on Hospital-Acquired Infection. N Engl J Med 2013;368:533-542


British Journal of Anaesthesia:     Therapeutic Hypothermia for Traumatic Brain Injury

Georgiou performed a systematic review (18 studies, 1851 patients) to evaluate the effect of therapeutic hypothermia initiated on presentation of the patient on both mortality and neurological outcome in patients with traumatic brain injury. The overall relative risk of mortality with therapeutic hypothermia when compared with controls was 0.84 [95% CI 0.72–0.98] and of poor neurological outcome was 0.81 (95% CI=0.73–0.89). However, when only high-quality trials were analysed, the relative risks were 1.28 (95% CI=0.89–1.83) and 1.07 (95% CI=0.92–1.24), respectively. Hypothermia was associated with cerebrovascular disturbances on rewarming and possibly with pneumonia in adult patients. Conclusion: Given the quality of the data currently available, no benefit of PTH on mortality or neurological morbidity could be identified.

Abstract:  Georgiou. Role of therapeutic hypothermia in improving outcome after traumatic brain injury. Br J Anaesth 2013;epublished January 25th


British Journal of Anaesthesia:     Critical Care in End Stage Renal Failure

Arulkumaran and colleagues completed a systematic review (16 studies, 6591 admissions) to describe the characteristics of ICU patients with endstage renal failure (ESRD). Cardiovascular disease and sepsis accounted for the majority of admissions. Acute illness severity scores tend to overestimate mortality among ESRD patients. Critical illness associated with acute kidney injury requiring renal replacement therapy was associated with significantly higher hospital mortality compared with ESRD patients admitted to the ICU [odds ratio 3.9; 3.5–4.4; P<0.0001]. Hospital mortality was less favourable compared with matched patients with mild AKI (OR 1.5; 1.4–1.6; P<0.0001). Although the mortality rate remains high shortly after hospital discharge, the duration of increased mortality risk is unclear. Conclusion: Patients with ESRD frequently benefit from ICU admission, despite chronic co-morbidity.

Abstract: Arulkumaran. Patients with end-stage renal disease admitted to the intensive care unit: systematic review. Br J Anaesth 2013;110(1):13-20


Stroke:     Blood Pressure Control in Intracerebral Haemorrhage

Butcher et al performed a randomized controlled trial in 75 patients with a spontaneous intracerebral haemorrhage less than 24 hours old, and with a systolic BP > 150 mm Hg, to test whether cerebral blood flow in acute intracerebral haemorrhage patients is affected by blood pressure reduction.  Patients underwent computed tomography perfusion imaging 2 hours postrandomization.  Mean systolic BP 2 hours after randomization was significantly lower in the <150 mm Hg target group (140±19 vs 162±12 mm Hg; P<0.001). The primary end point of perihematoma relative cerebral blood flow in the <150 mm Hg target group (0.86±0.12) was not significantly lower than that in the <180 mm Hg group (0.89±0.09; P=0.19; absolute difference, 0.03; 95% CI 0.018 to 0.078). There was no relationship between the magnitude of BP change and perihematoma relative cerebral blood flow in the <150 mm Hg (R=0.00005; 95% CI 0.001 to 0.001) or <180 mm Hg target groups (R=0.000; 95% CI −0.001 to 0.001). Conclusions—Rapid blood pressure lowering after a moderate volume of intracerebral haematoma does not reduce perihematoma cerebral blood flow.

Abstract:  Butcher. The Intracerebral Hemorrhage Acutely Decreasing Arterial Pressure Trial (ICH ADAPT trial). Stroke 2013;epublished ahead of print


Cochrane Reviews



Circulation:     Ischaemic Stroke


Anaesthesia:     Post-Operative Recovery


BMC Medicine:     Publication Standards



Emergency Medicine Australasia:     Medical Reversal


Journal of Antimicrobial Chemotherapy:     Carbapenemase-producing Enterobacteriaceae


Journal of Antimicrobial Chemotherapy:     Multi-Resistant Gram Negative Bacteria


Journal of Antimicrobial Chemotherapy:     Neutropaenic Cancer Patients


Daru Journal of Pharmaceutical Sciences:     Nanomedicine in Emergency Medicine


European Journal of Anaesthesiology:     Death under Anaesthesia



Emergency Medicine News:     FOAM


Review - Clinical


Therapeutic Hypothermia in Brain Injury. Edited by Farid Sadaka, ISBN 978-953-51-0960-0, Hard cover, 148 pages, Publisher: InTech, Published: January 30, 2013



Journal of the American College of Cardiology:     High-Sensitivity Troponin

Journal of the American College of Cardiology:     Troponin

Interactive Cardiovascular & Thoracic Surgery:     Anticoagulation for a LVAD


JACC Heart Failure:     Heart Failure


Journal of the American College of Cardiology:     Mitochondria in Heart Failure


Indian Journal of Medical Research:     Drug-Eluting Stents



World Journal of Hepatology:     Cirrhosis


American Journal of Nephrology:    Stem Cells in Renal Ischaemia



Journal of Diabetes and Endocrinology


Journal of Intensive Care Medicine:    Intra-Abdominal Infections


Annals of Internal Medicine:     Iatrogenic Fungal Infection



Collegium Antropologicum:     Pelvic Fracture


Emergency Medicine International:     Combat Vascular Injuries



Daru Journal of Pharmaceutical Sciences:     Sulphur Mustard Injury



Emergency Medicine Australasia:     Shocked Neonate


European Journal of Cardiothoracic Surgery:     Paediatric Heart Transplantation



Emergency Medicine International:     Full Body Radiography



I hope you find these brief summaries and links useful.

Until next week