Severe trauma continues to represent a global public health issue and mortality and morbidity in trauma patients remains substantial. A number of initiatives have aimed to provide guidance on the management of trauma patients. This document focuses on the management of major bleeding and coagulopathy following trauma and encourages adaptation of the guiding principles to each local situation and implementation within each institution. The pan-European, multidisciplinary Task Force for Advanced Bleeding Care in Trauma was founded in 2004 and included representatives of six relevant European professional societies. The group used a structured, evidence-based consensus approach to address scientific queries that served as the basis for each recommendation and supporting rationale. Expert opinion and current clinical practice were also considered, particularly in areas in which randomised clinical trials have not or cannot be performed. Existing recommendations were reconsidered and revised based on new scientific evidence and observed shifts in clinical practice; new recommendations were formulated to reflect current clinical concerns and areas in which new research data have been generated. This guideline represents the fourth edition of a document first published in 2007 and updated in 2010 and 2013. The guideline now recommends that patients be transferred directly to an appropriate trauma treatment centre and encourages use of a restricted volume replacement strategy during initial resuscitation. Best-practice use of blood products during further resuscitation continues to evolve and should be guided by a goal-directed strategy. The identification and management of patients pre-treated with anticoagulant agents continues to pose a real challenge, despite accumulating experience and awareness. The present guideline should be viewed as an educational aid to improve and standardise the care of the bleeding trauma patients across Europe and beyond. This document may also serve as a basis for local implementation. Furthermore, local quality and safety management systems need to be established to specifically assess key measures of bleeding control and outcome. A multidisciplinary approach and adherence to evidence-based guidance are key to improving patient outcomes. The implementation of locally adapted treatment algorithms should strive to achieve measureable improvements in patient outcome.

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The European guideline on management of major bleeding and coagulopathy following trauma: fourth edition

Summary Background Not all patients infected with NDM-1-positive bacteria have a history of hospital admission in India, and extended-spectrum β-lactamases are known to be circulating in the Indian community. We therefore measured the prevalence of the NDM-1 gene in drinking water and seepage samples in New Delhi. Methods Swabs absorbing about 100 μL of seepage water (ie, water pools in streets or rivulets) and 15 mL samples of public tap water were collected from sites within a 12 km radius of central New Delhi, with each site photographed and documented. Samples were transported to the UK and tested for the presence of the NDM-1 gene, bla NDM-1 , by PCR and DNA probing. As a control group, 100 μL sewage effluent samples were taken from the Cardiff Wastewater Treatment Works, Tremorfa, Wales. Bacteria from all samples were recovered and examined for bla NDM-1 by PCR and sequencing. We identified NDM-1-positive isolates, undertook susceptibility testing, and, where appropriate, typed the isolates. We undertook Inc typing on bla NDM-1 -positive plasmids. Transconjugants were created to assess plasmid transfer frequency and its relation to temperature. Findings From Sept 26 to Oct 10, 2010, 171 seepage samples and 50 tap water samples from New Delhi and 70 sewage effluent samples from Cardiff Wastewater Treatment Works were collected. We detected bla NDM-1 in two of 50 drinking-water samples and 51 of 171 seepage samples from New Delhi; the gene was not found in any sample from Cardiff. Bacteria with bla NDM-1 were grown from 12 of 171 seepage samples and two of 50 water samples, and included 11 species in which NDM-1 has not previously been reported, including Shigella boydii and Vibrio cholerae . Carriage by enterobacteria, aeromonads, and V cholera was stable, generally transmissible, and associated with resistance patterns typical for NDM-1; carriage by non-fermenters was unstable in many cases and not associated with typical resistance. 20 strains of bacteria were found in the samples, 12 of which carried bla NDM-1 on plasmids, which ranged in size from 140 to 400 kb. Isolates of Aeromonas caviae and V cholerae carried bla NDM-1 on chromosomes. Conjugative transfer was more common at 30°C than at 25°C or 37°C. Interpretation The presence of NDM-1 β-lactamase-producing bacteria in environmental samples in New Delhi has important implications for people living in the city who are reliant on public water and sanitation facilities. International surveillance of resistance, incorporating environmental sampling as well as examination of clinical isolates, needs to be established as a priority. Funding European Union.

https://www.thelancet.com/pdfs/journals/laninf/PIIS1473-3099(11)70059-7.pdf

Dissemination of NDM-1 positive bacteria in the New Delhi environment and its implications for human health: an environmental point prevalence study

The aims of severe perioperative bleeding management are three-fold. First, preoperative identification by anamesis and laboratory testing of those patients for whom the perioperative bleeding risk may be increased. Second, implementation of strategies for correcting preoperative anaemia and stabilisation of the macro- and microcirculations in order to optimise the patient’s tolerance to bleeding. Third, targeted procoagulant interventions to reduce the amount of bleeding, morbidity, mortality and costs. The purpose of these guidelines is to provide an overview of current knowledge on the subject with an assessment of the quality of the evidence in order to allow anaesthetists throughout Europe to integrate this knowledge into daily patient care wherever possible. The Guidelines Committee of the European Society of Anaesthesiology (ESA) formed a task force with members of scientific subcommittees and individual expert members of the ESA. Electronic databases were searched without language restrictions from the year 2000 until 2012. These searches produced 20 664 abstracts. Relevant systematic reviews with meta-analyses, randomised controlled trials, cohort studies, case-control studies and cross-sectional surveys were selected. At the suggestion of the ESA Guideline Committee, the Scottish Intercollegiate Guidelines Network (SIGN) grading system was initially used to assess the level of evidence and to grade recommendations. During the process of guideline development, the official position of the ESA changed to favour the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. This report includes general recommendations as well as specific recommendations in various fields of surgical interventions. The final draft guideline was posted on the ESA website for four weeks and the link was sent to all ESA members. Comments were collated and the guidelines amended as appropriate. When the final draft was complete, the Guidelines Committee and ESA Board ratified the guidelines.

https://epub.ub.uni-muenchen.de/24023/1/oa_24023.pdf

Management of severe perioperative bleeding Guidelines from the European Society of Anaesthesiology

The management of perioperative bleeding involves multiple assessments and strategies to ensure appropriate patient care. Initially, it is important to identify those patients with an increased risk of perioperative bleeding. Next, strategies should be employed to correct preoperative anaemia and to

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Management of severe perioperative bleeding: guidelines from the European Society of Anaesthesiology: First update 2016.

Summary Metallo-β-lactamases are resistance determinants of increasing clinical relevance in Gram-negative bacteria. Because of their broad range, potent carbapenemase activity and resistance to inhibitors, these enzymes can confer resistance to almost all β-lactams. Since the 1990s, several metallo-β-lactamases encoded by mobile DNA have emerged in important Gram-negative pathogens (ie, in Enterobacteriaceae, Pseudomonas aeruginosa , and Acinetobacter baumannii ). Some of these enzymes (eg, VIM-1 and NDM-1) have been involved in the recent crisis resulting from the international dissemination of carbapenem-resistant Klebsiella pneumoniae and other enterobacteria. Although substantial knowledge about the molecular biology and genetics of metallo-β-lactamases is available, epidemiological data are inconsistent and clinical experience is still lacking; therefore, several unsolved or debatable issues remain about the management of infections caused by producers of metallo-β-lactamase. The spread of metallo-β-lactamases presents a major challenge both for treatment of individual patients and for policies of infection control, exposing the substantial unpreparedness of public health structures in facing up to this emergency.

https://www.thelancet.com/pdfs/journals/laninf/PIIS1473-3099(11)70056-1.pdf

Metallo-β-lactamases: a last frontier for β-lactams?

INTRODUCTION The current investigation aimed to study the efficacy of hemostatic therapy guided either by conventional coagulation analyses or point-of-care (POC) testing in coagulopathic cardiac surgery patients. METHODS Patients undergoing complex cardiac surgery were assessed for eligibility. Those patients in whom diffuse bleeding was diagnosed after heparin reversal or increased blood loss during the first 24 postoperative hours were enrolled and randomized to the conventional or POC group. Thromboelastometry and whole blood impedance aggregometry have been performed in the POC group. The primary outcome variable was the number of transfused units of packed erythrocytes during the first 24 h after inclusion. Secondary outcome variables included postoperative blood loss, use and costs of hemostatic therapy, and clinical outcome parameters. Sample size analysis revealed a sample size of at least 100 patients per group. RESULTS There were 152 patients who were screened for eligibility and 100 patients were enrolled in the study. After randomization of 50 patients to each group, a planned interim analysis revealed a significant difference in erythrocyte transfusion rate in the conventional compared with the POC group [5 (4;9) versus 3 (2;6) units [median (25 and 75 percentile)], P<0.001]. The study was terminated early. The secondary outcome parameters of fresh frozen plasma and platelet transfusion rates, postoperative mechanical ventilation time, length of intensive care unit stay, composite adverse events rate, costs of hemostatic therapy, and 6-month mortality were lower in the POC group. CONCLUSIONS Hemostatic therapy based on POC testing reduced patient exposure to allogenic blood products and provided significant benefits with respect to clinical outcomes.

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Point-of-care testing: a prospective, randomized clinical trial of efficacy in coagulopathic cardiac surgery patients.

Objective
Evaluation of the technical and diagnostic feasibility of commercial multiplex real-time polymerase chain reaction (PCR) for detection of blood stream infections in a cohort of intensive care unit (ICU) patients with severe sepsis, performed in addition to conventional blood cultures.

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Improved detection of blood stream pathogens by real-time PCR in severe sepsis.

Karthikeyan Kumarasamy and colleagues express concern about the emergence of New Delhi metallo-βlactamase (NDM-1) in enterobacteria in India, Pakistan, and the UK. One of the fi rst acquired metallo-βlactamase-producing enterobacteria reported was an IMP-1-producing Klebsiella pneumoniae isolated in Singapore in 1996. Since then we have undertaken hospital surveillance for carbapenem-resistant enterobacteria. Until 2009, the only other metallo-β-lactamase enterobacteria we isolated was another unrelated IMP-1-producing K pneumoniae in 2004. In early 2010, we isolated two K pneumoniae with a high level of resistance (determined by Etest; bioMérieux, Marcy l’Etoile, France) to many antibiotics including to carbapenems (table). The fi rst—DU1301/10—was from the urine of a patient who had just returned from a 5-month stay in India where he had an indwelling catheter inserted. The second isolate, DU7433/10, was from THK, CTK, and TYK did the experimental work to identify the β-lactamase genes, and did the typing studies. LW, YLL, HNL, and LCL managed and provided background information about the two cases. All authors were involved in writing the letter. We declare that we have no confl icts of interest.

CorrespondenceGlobal spread of New Delhi metallo-β-lactamase 1

Point of Care Testing: A Prospective, Randomized Clinical Trial of Efficacy in Coagulopathic Cardiac Surgery Patients

Procalcitonin (PCT) is known to be a reliable biomarker of sepsis and infection. Elevation of serum or plasma PCT has also been observed after major surgery or trauma. The association of PCT with the severity or location of injury in multiple traumatized (polytrauma) patients has not been clearly established, to date. The aim of this study was therefore to evaluate the sensitivity of PCT as a biomarker for the diagnosis of abdominal trauma. In a prospective clinical study, PCT, interrleukin-6, and C-reactive protein were measured in blood (serum) samples obtained in the emergency room (D0) from 74 patients with multiple injuries and in serum samples obtained on the 2 days after trauma (D1, D2). PCT significantly increased during the first two posttraumatic days in patients with severe multiple injuries (n = 24, day 1: 3.37 ng/mL +/- 0.92 ng/mL; day 2: 3.27 ng/mL +/-0.97 ng/mL) as compared with patients with identical Injury Severity Score but without abdominal injury (day 1: 0.6 ng/mL +/- 0.18 ng/mL; 0.61 ng/mL +/- 0.21 ng/mL). Interrleukin-6 and C-reactive protein serum levels were not able to discriminate between patients with and without abdominal injury during the 2-day posttrauma observation period. In a specific evaluation of the abdominal injury pattern, a significant increase of serum PCT concentrations was observed on day 1 after trauma of the liver (4.04 ng/mL +/- 0.99 ng/mL) and the gut (4.63 ng/mL +/- 1.12 ng/mL) compared with other abdominal lesions (0.62 ng/mL +/- 0.2 ng/mL). Markedly elevated PCT concentrations were also evident after severe multiple injuries, including the liver/spleen in combination with thorax trauma (9.37 ng/mL +/- 2.71 ng/mL). Assessment of serum PCT seems to be significantly increased after abdominal trauma in severe multiple traumatized patients and may serve as a useful biomarker to support other diagnostic methods including ultrasound and CT scan. Although elevated levels of PCT during the first 2 days after trauma are more likely to be indicative of traumatic impact than of an ongoing status of sepsis, multiple events such as surgery, massive transfusion, and intensive care therapy might influence the PCT concentration.

Tobias M. Bingold

Papers

Point-of-care testing: a prospective, randomized clinical trial of efficacy in coagulopathic cardiac surgery patients.

Improved detection of blood stream pathogens by real-time PCR in severe sepsis.

CorrespondenceGlobal spread of New Delhi metallo-β-lactamase 1

Point of Care Testing: A Prospective, Randomized Clinical Trial of Efficacy in Coagulopathic Cardiac Surgery Patients

Serum procalcitonin levels in patients with multiple injuries including visceral trauma