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Background: Iron supplementation and erythropoiesis-stimulating agent (ESA) administration represent the hallmark therapies in preoperative anemia treatment, as reflected in a set of evidence-based treatment recommendations made during the 2018 International Consensus Conference on Patient Blood Management. However, little is known about the safety of these therapies. This systematic review investigated the occurrence of adverse events (AEs) during or after treatment with iron and/or ESAs., Methods: Five databases (The Cochrane Library, MEDLINE, Embase, Transfusion Evidence Library, Web of Science) and two trial registries (ClinicalTrials.gov, WHO ICTRP) were searched until 23 May 2022. Randomized controlled trials (RCTs), cohort, and case-control studies investigating any AE during or after iron and/or ESA administration in adult elective surgery patients with preoperative anemia were eligible for inclusion and judged using the Cochrane Risk of Bias tools. The GRADE approach was used to assess the overall certainty of evidence., Results: Data from 26 RCTs and 16 cohort studies involving a total of 6062 patients were extracted, on 6 treatment comparisons: (1) intravenous (IV) versus oral iron, (2) IV iron versus usual care/no iron, (3) IV ferric carboxymaltose versus IV iron sucrose, (4) ESA+iron versus control (placebo and/or iron, no treatment), (5) ESA+IV iron versus ESA+oral iron, and (6) ESA+IV iron versus ESA+IV iron (different ESA dosing regimens). Most AE data concerned mortality/survival (n=24 studies), thromboembolic (n=22), infectious (n=20), cardiovascular (n=19) and gastrointestinal (n=14) AEs. Very low certainty evidence was assigned to all but one outcome category. This uncertainty results from both the low quantity and quality of AE data due to the high risk of bias caused by limitations in the study design, data collection, and reporting., Conclusions: It remains unclear if ESA and/or iron therapy is associated with AEs in preoperatively anemic elective surgery patients. Future trial investigators should pay more attention to the systematic collection, measurement, documentation, and reporting of AE data., (© 2022. The Author(s).)

Objectives: For anaemic elective surgery patients, current clinical practice guidelines weakly recommend the routine use of iron, but not erythrocyte-stimulating agents (ESAs), except for short-acting ESAs in major orthopaedic surgery. This recommendation is, however, not based on any cost-effectiveness studies. The aim of this research was to (1) systematically review the literature regarding cost effectiveness of preoperative iron and/or ESAs in anaemic, elective surgery patients and (2) update existing economic evaluations (EEs) with recent data., Methods: Eight databases and registries were searched for EEs and randomized controlled trials (RCTs) reporting cost-effectiveness data on November 11, 2020. Data were extracted, narratively synthesized and critically appraised using the Philips reporting checklist. Pre-existing full EEs were updated with effectiveness data from a recent systematic review and current cost data. Incremental cost-effectiveness ratios were expressed as cost per (quality-adjusted) life-year [(QA)LY] gained., Results: Only five studies (4 EEs and 1 RCT) were included, one on intravenous iron and four on ESAs + oral iron. The EE on intravenous iron only had an in-hospital time horizon. Therefore, cost effectiveness of preoperative iron remains uncertain. The three EEs on ESAs had a lifetime time horizon, but reported cost per (QA)LY gained of 20-65 million (GBP or CAD). Updating these analyses with current data confirmed ESAs to have a cost per (QA)LY gained of 3.5-120 million (GBP or CAD)., Conclusions: Cost effectiveness of preoperative iron is unproven, whereas routine preoperative ESA therapy cannot be considered cost effective in elective surgery, based on the limited available data. Future guidelines should reflect these findings., (© 2021. The Author(s).)

Background and Objectives: Equipoise remains on the optimal transfusion strategy in surgical oncologic patients. The primary objective of our study was to determine the impact of anaemia and red blood cells (RBCs) transfusion on severe postoperative complications in surgical oncologic critically ill patients., Materials and Methods: Retrospective single-centre study. Adults admitted to intensive care unit after major oncologic surgery were eligible. Analyses to determine the independent risk factors, including anaemia or RBC transfusion, for postoperative complications and/or hospital mortality were performed., Results: Of the 283 patients included, 246 patients (86.9%) had anaemia. Fifty-five patients (19·4%) were transfused. Patients exposed to moderate-to-severe anaemia or RBC transfusion had more often severe complications, especially acute kidney injury and infectious complications. Multivariate analysis found an independent association between moderate and severe anaemia and severe postoperative complications (moderate anaemia: OR 14·02 [2·52-264]; severe anaemia: OR 16·25 [2·62-318·5]; P < 0·05). Elderly, obese patients and patients operated from abdominal surgery appeared to be more vulnerable to anaemia than other patients. Transfusion was also an independent risk factor for postoperative complications (OR 4·19 [2·12-8·39]; P < 0·001). When considering moderate-to-severe anaemic patients, RBC transfusion was no longer associated with postoperative complications., Conclusions: Anaemia was associated with severe postoperative complications, and this association was stronger in elderly, obese patients and after abdominal surgery. RBC transfusion also negatively impacts on patients' prognosis. However, this association was not found in case of moderate-to-severe anaemia exposure (haemoglobin < 10 g/dl)., (© 2021 International Society of Blood Transfusion.)

Patient Blood Management (PBM) is an evidence-based, multidisciplinary, patient-centred approach to optimizing the care of patients who might need a blood transfusion. This systematic review aimed to collect the best available evidence on the effectiveness of preoperative iron supplementation with or without erythropoiesis-stimulating agents (ESAs) on red blood cell (RBC) utilization in all-cause anaemic patients scheduled for elective surgery. Five databases and two trial registries were screened. Primary outcomes were the number of patients and the number of RBC units transfused. Effect estimates were synthesized by conducting meta-analyses. GRADE (Grades of Recommendation, Assessment, Development and Evaluation) was used to assess the certainty of evidence. We identified 29 randomized controlled trials (RCTs) and 2 non-RCTs comparing the effectiveness of preoperative iron monotherapy, or iron + ESAs, to control (no treatment, usual care, placebo). We found that: (1) IV and/or oral iron monotherapy may not result in a reduced number of units transfused and IV iron may not reduce the number of patients transfused (low-certainty evidence); (2) uncertainty exists whether the administration route of iron therapy (IV vs oral) differentially affects RBC utilization (very low-certainty evidence); (3) IV ferric carboxymaltose monotherapy may not result in a different number of patients transfused compared to IV iron sucrose monotherapy (low-certainty evidence); (4) oral iron + ESAs probably results in a reduced number of patients transfused and number of units transfused (moderate-certainty evidence); (5) IV iron + ESAs may result in a reduced number of patients transfused (low-certainty evidence); (6) oral and/or IV iron + ESAs probably results in a reduced number of RBC units transfused in transfused patients (moderate-certainty evidence); (7) uncertainty exists about the effect of oral and/or IV iron + ESAs on the number of patients requiring transfusion of multiple units (very low-certainty evidence). Effect estimates of different haematological parameters and length of stay were synthesized as secondary outcomes. In conclusion, in patients with anaemia of any cause scheduled for elective surgery, the preoperative administration of iron monotherapy may not result in a reduced number of patients or units transfused (low-certainty evidence). Iron supplementation in addition to ESAs probably results in a reduced RBC utilization (moderate-certainty evidence)., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Despite numerous studies, controversies about the best intraoperative FiO 2 remain. In 2016, the World Health Organization (WHO) recommended that adult patients undergoing general anaesthesia should be ventilated intraoperatively with an 80% FiO 2 to reduce surgical site infection (SSI). However, several data suggest that hyperoxia could have adverse effects. In order to determine the potential effect of FiO 2 on SSI, we included in this systematic review 23 studies (among which 21 randomised controlled trials [RCT]) published between 1999 and 2020, comparing intraoperative high versus low FiO 2 . Results were heterogeneous but most recent studies on one hand, and the largest RCTs on the other hand, reported no difference on the incidence of SSI regarding intraoperative FiO 2 during general anaesthesia. There was also no difference in the incidence of SSI depending of intraoperative FiO 2 in patients receiving regional anaesthesia. The review on secondary endpoints (respiratory and cardiovascular adverse events, postoperative nausea and vomiting, postoperative length-of-stay and mortality) also failed to support the use of high FiO 2 . On the opposite, some data from follow-up analyses and registry studies suggested a possible negative effect of high intraoperative FiO 2 on long-term outcomes. In conclusion, the systematic administration of a high intraoperative FiO 2 in order to decrease SSI or improve other perioperative outcomes seems unjustified in the light of the evidence currently available in the literature., (Copyright © 2020 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.)

Background: An acute traumatic coagulopathy (ATC) is observed in about one third of severely traumatized patients. This early, specific, and endogenous disorder is triggered by the association of trauma and hemorrhage. The early phase of this condition is characterized by the expression of a bleeding phenotype leading to hemorrhagic shock and the late phase by a prothrombotic profile leading to multiple organ failure. The physiopathology of this phenomenon is still poorly understood. Hypotheses of disseminated intravascular coagulation, activated protein C-mediated fibrinolysis, fibrinogen consumption, and platelet functional impairment were developed by previous authors and continue to be debated. The objective of this study was to observe general hemostasis disorders in case of ATC to confront these hypotheses., Method: Four groups of 15 rats were compared: C, control; T, trauma; H, hemorrhage; and TH, trauma and hemorrhage. Blood samples were drawn at baseline and 90 min. Thrombin generation tests, platelet aggregometry, and standard hemostasis tests were performed., Results: Significant differences were observed between the baseline and TH groups for aPTT (17.9 ± 0.8 s vs 24.3 ± 1.4 s, p < 0.001, mean ± SEM), MAP (79.7 ± 1.3 mmHg vs 43.8 ± 1.3 mmHg, p < 0.001, mean ± SEM), and hemoglobin (16.5 ± 0.1 g/dL vs 14.1 ± 0.3 g/dL, p < 0.001, mean ± SEM), indicating the presence of an hemorrhagic shock due to ATC. Compared to all other groups, coagulation factor activities were decreased in the TH group, but endogenous thrombin potential was (paradoxically) higher than in group C (312 ± 17 nM/min vs. 228 ± 23 nM/min; p = 0.016; mean ± SEM). We also observed a subtle decrease in platelet count and function in case of ATC and retrieved an inversed linear relationship between fibrinogen concentration and aPTT (intercept, 26.53 ± 3.16; coefficient, - 3.40 ± 1.26; adjusted R 2 : 0.1878; p = 0.0123)., Conclusions: The clinical-biological profile that we observed, combining normal thrombin generation, fibrinogen depletion, and a hemorrhagic phenotype, reinforced the hypothesis of activated protein C mediated-fibrinolysis. The key role of fibrinogen, but not of the platelets, was confirmed in this study. The paradoxical preservation of thrombin generation suggests a protective mechanism mediated by rhabdomyolysis in case of major trauma. Based on these results, we propose a new conception concerning the pathophysiology of ATC., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s). 2019.)

Haemorrhagic shock is a rare occurrence in emergency medicine but it can be associated with significant mortality. The purpose of this study was to evaluate the impact of a major haemorrhage protocol on patient management in Emergency Department Resuscitation Area., Methods: A single-centre study was conducted to compare two periods, before and after institution of a massive haemorrhage protocol including the use of massive transfusion orders and the availability of packed red blood cell concentrates prior to patient's admission. Two groups of patients (in both trauma and non-trauma settings) were defined: "before protocol" and "after protocol". The primary outcome was the median transfusion time for a unit of red blood cell concentrate., Results: Forty patients were included: 22 for the "pre-protocol" group and 18 for the "post-protocol" group. The two groups were balanced with baseline characteristics. This study showed a significantly reduced median transfusion time for a unit of red blood cell concentrate from 20min pre-protocol to 9min post-protocol. The time between patient's admission and transfusion of the first red blood cell concentrate was reduced but non-significantly from 71min to 36min., Conclusion: The major haemorrhage protocol optimised patient management by reducing the median transfusion time for red blood cell concentrates., (Copyright © 2018. Published by Elsevier Masson SAS.)

Background: Immersion can cause immersion pulmonary edema (IPE) in previously healthy subjects. We performed a case-control study to better identify IPE risk factors., Methods: We prospectively included recreational scuba divers who had presented signs of IPE and control divers who were randomly chosen among diving members of the French Underwater Federation. We sent an anonymous questionnaire to each diver, with questions on individual characteristics, as well as the conditions of the most recent dive (controls) or the dive during which IPE occurred. Univariate logistic regressions were performed for each relevant factor. Then, multivariate logistic regression was performed., Results: Of the 882 questionnaires sent, 480 (54%) were returned from 88 cases (90%) and 392 control divers (50%). Multivariate analysis identified the following independent risk factors associated with IPE: being aged over 50 years ((OR) 3.30, (95%CI) 1.76-6.19); female sex (OR 2.20, 95%CI 1.19-4.08); non-steroidal anti-inflammatory drug (NSAID) intake before diving (OR 24.32, 95%CI 2.86-206.91); depth of dive over 20 m (OR 2.00, 95%CI 1.07-3.74); physical exertion prior to or during the dive (OR 5.51, 95%CI 2.69-11.28); training dive type (OR 5.34, 95%CI 2.62-10.86); and daily medication intake (OR 2.79, 95%CI 1.50-5.21); this latter factor appeared to be associated with hypertension in the univariate analysis., Conclusion: To reduce the risk of experiencing IPE, divers over 50 years of age or with hypertension, especially women, should avoid extensive physical effort, psychological stress, deep dives and NSAID intake before diving., Competing Interests: The authors of this paper declare no conflicts of interest exist with this submission., (Copyright© Undersea and Hyperbaric Medical Society.)

Importance: Blood transfusion is one of the most frequently used therapies worldwide and is associated with benefits, risks, and costs., Objective: To develop a set of evidence-based recommendations for patient blood management (PBM) and for research., Evidence Review: The scientific committee developed 17 Population/Intervention/Comparison/Outcome (PICO) questions for red blood cell (RBC) transfusion in adult patients in 3 areas: preoperative anemia (3 questions), RBC transfusion thresholds (11 questions), and implementation of PBM programs (3 questions). These questions guided the literature search in 4 biomedical databases (MEDLINE, EMBASE, Cochrane Library, Transfusion Evidence Library), searched from inception to January 2018. Meta-analyses were conducted with the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology and the Evidence-to-Decision framework by 3 panels including clinical and scientific experts, nurses, patient representatives, and methodologists, to develop clinical recommendations during a consensus conference in Frankfurt/Main, Germany, in April 2018., Findings: From 17 607 literature citations associated with the 17 PICO questions, 145 studies, including 63 randomized clinical trials with 23 143 patients and 82 observational studies with more than 4 million patients, were analyzed. For preoperative anemia, 4 clinical and 3 research recommendations were developed, including the strong recommendation to detect and manage anemia sufficiently early before major elective surgery. For RBC transfusion thresholds, 4 clinical and 6 research recommendations were developed, including 2 strong clinical recommendations for critically ill but clinically stable intensive care patients with or without septic shock (recommended threshold for RBC transfusion, hemoglobin concentration <7 g/dL) as well as for patients undergoing cardiac surgery (recommended threshold for RBC transfusion, hemoglobin concentration <7.5 g/dL). For implementation of PBM programs, 2 clinical and 3 research recommendations were developed, including recommendations to implement comprehensive PBM programs and to use electronic decision support systems (both conditional recommendations) to improve appropriate RBC utilization., Conclusions and Relevance: The 2018 PBM International Consensus Conference defined the current status of the PBM evidence base for practice and research purposes and established 10 clinical recommendations and 12 research recommendations for preoperative anemia, RBC transfusion thresholds for adults, and implementation of PBM programs. The relative paucity of strong evidence to answer many of the PICO questions supports the need for additional research and an international consensus for accepted definitions and hemoglobin thresholds, as well as clinically meaningful end points for multicenter trials.

Objectives: The European trauma guidelines were developed to assist clinicians in the early phase of trauma management to diagnose and treat coagulopathy and bleeding. This study aimed to determine compliance with these European trauma guidelines in a French referral trauma centre., Methods: Medical charts of trauma patients with an injury severity score≥16 admitted between January 2013 and December 2014 were reviewed. Compliance with 21 recommendations in the first 24-hours of patient management was assessed., Results: There were 145 patients with median ISS of 34 [IQR 25-41]. A good level of compliance (i.e. applied in≥80% of patients) was identified for nine recommendations, inconsistent compliance (i.e. applied in 50 to 79% of patients) for six recommendations, including fibrinogen levels at hospital admission and achievement of a target mean arterial blood pressure (MAP)>80mmHg in patients with major bleeding and TBI (55.5%), and poor compliance (i.e. applied in<50% of patients) for another six recommendations. Poorly applied recommendations included early measurement of lactate or base deficit (32%), early administration of tranexamic acid (18%), and achievement of normocapnia in patients with TBI undergoing invasive ventilation (3%)., Conclusions: In a referral trauma centre, nine of the 21 evaluable recommendations in the European trauma guidelines were applied in≥80% of patients. Early diagnosis and treatment of trauma-related coagulopathy was identified as an area for significant practice improvement. In patients with TBI, efforts should be made to achieve the targeted MAP and to maintain normocapnia., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Plasma for direct therapeutic use is a fast-evolving blood component in terms of its production and presentation. More than a dozen forms are available worldwide, which is often overlooked since most countries apply policies making only one or very few forms available for treating patients in need. It is most often reserved for the same three clinical indications, i.e. overall clotting-factor deficiency, reversal of vitamin K antagonists in the context of active bleeding or prior to urgent surgery, and therapeutic plasma exchange. The level of evidence is often less robust than generally acknowledged for such major indications while novel indications are tending to emerge in medical and trauma settings. This short review explores classical views and new prospects opened up by novel presentations and statuses for therapeutic plasma., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Objectives: Transfusion-related adverse events (TRAE) can contribute to patient morbidity and mortality. In this brief narrative review, the strategies that clinicians can apply at the bedside to avoid TRAE are discussed., Methods: Strategies to avoid the following five types of TRAE were reviewed: transfusion-associated circulatory overload (TACO), transfusion-related acute lung injury (TRALI), transfusion-associated hypothermia (TAH), transfusion-related allergic reactions (TRAR) and acute haemolytic transfusion reactions (AHTR)., Results: Minimizing exposure to blood components is fundamental to TRAE avoidance. Pre-transfusion assessment can identify patients at risk of TACO, TRAR and TAH, and avoidance steps implemented. Preventive strategies for TACO include lower transfusion rate, 'one unit at a time' transfusion policy and possibly diuretic medication. Patients with past history of TRAR should preferably be given plasma-free blood components; anti-histamine medication prior to transfusion could be considered. TAH is common in the massive transfusion setting, particularly trauma patients. Warming of patients are key strategies to avoid TAH. Identification of patients at risk of TRALI is more opaque; however, any measures that limit pulmonary inflammation prior to transfusion may decrease the risk of TRALI. Causes of AHTR are commonly due to human error and failure to apply rigorous cross-checks of patient and issued RBC component blood groups., Conclusions: Beneficial strategies to avoid TRAE include judicious use of blood components, identification of high-risk patients, adherence to recommended clinical processes and awareness of TRAE pathophysiology. More evidence is warranted to better guide clinicians in the prevention of TRAE., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Background: Platelets (PLTs) are usually stored for up to 5 days prior to transfusion, although in some blood services the storage period is extended to 7 days. During storage, changes occur in both PLT and storage medium, which may lead to PLT activation and dysfunction. The clinical significance of these changes remains uncertain., Methods: We performed a systematic review to assess the association between PLT storage time and clinical or transfusion outcomes in patients receiving allogeneic PLT transfusion. We searched studies published in English between January 2000 and July 2017 identified from MEDLINE, Embase, PubMed and the Cochrane Libraries., Results: Of the 18 studies identified, five included 4719 critically ill patients (trauma, post-cardiac surgery and a heterogeneous population of critically ill patients) and 13 included 8569 haematology patients. The five studies in critically ill patients were retrospective and did not find any association between PLT storage time when PLTs were stored for up to 5 days and mortality. There was also no association between older PLTs and sepsis in the two largest studies (n = 4008 patients). Of the 13 studies in haematology patients, seven analysed prolonged storage time up to 6.5 or 7 days. Administration of fresh PLTs (less than 2 or 3 days) was associated with a significant increase in corrected count increment (CCI) compared to older PLTs in seven of the eight studies analysing this outcome. One single centre retrospective study found an increase in bleeding events in patients receiving older PLTs., Conclusions: PLT storage time does not appear to be associated with clinical outcomes, including bleeding, sepsis or mortality, in critically ill patients or haematology patients. The freshest PLTs (less than 3 days) were associated with a better CCI, although there was no impact on bleeding events, questioning the clinical significance of this association. However, there is an absence of evidence to draw definitive conclusions, especially in critically ill patients.

The consumption of fibrinogen concentrates has been increasing steadily for several years in surgery, trauma and obstetrics. However, data from the literature are conflicting. The French Working Group on Perioperative Haemostasis (GIHP) proposes a position paper based on a narrative review of the literature, and addresses the following questions: What is the exact role of fibrinogen in haemostasis? Which rational support for the use of perioperative fibrinogen? Which thrombotic risk? What are the most recent professional recommendations on the use of fibrinogen concentrates? Then, evidence-based recommendations are proposed: 1) it is suggested not to administer prophylactic FC to prevent haemorrhage; 2) it is suggested not to use FC alone. Haemostatic treatment must be comprehensive, include other haemostatic treatments and must be limited in cases of severe active haemorrhage; 3) the GIHP suggests urgent measurement of fibrinogen plasma concentration in a biology laboratory or functional fibrinogen by viscoelastic methods. The choice between the two methods must be guided by the time to receive the results from a certified organisation with, in particular, authorisation to perform delocalised biologic examinations; 4) it is suggested not to administer FC when the fibrinogen concentration is superior to 1.5g/L or when there is a functional fibrinogen deficit (with the possible exception in obstetrics where the threshold could be 2.0g/L); 5) if FC are administered, an initial dose of 25-50mg/kg is proposed., (Copyright © 2018 Société française d'anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.)

As a therapy or a support to other therapies, despite being largely beneficial to patients in general, transfusion it is not devoid of some risks. In a moderate number of cases, patients may manifest adverse reactions, otherwise referred to as transfusion-associated hazards (TAHs). The latest French 2016 haemovigilance report indicates that 93% of TAHs are minor (grade 1), 5.5% are moderate (grade 2) and 1.6% are severe (grade 3), with only five deaths (grade 4) being attributed to transfusion with relative certainty (imputability of level [or grade] 1 to 3). Health-care providers need to be well aware of the benefits and potential risks (to best evaluate and discuss the benefit-risk ratio), how to prevent TAHs, the overall costs and the availability of alternative therapeutic options. In high-income countries, most blood establishments (BEs) and hospital blood banks (HBBs) have developed tools for reporting and analysing at least severe transfusion reactions. With nearly two decades of haemovigilance, transfusion reaction databases should be quite informative, though there are four main caveats that prevent it from being fully efficient: (ai) reporting is mainly declarative and is thus barely exhaustive even in countries where it is mandatory by law; (aii) it is often difficult to differentiate between the different complications related to transfusion, diseases, comorbidities and other types of therapies in patients suffering from debilitating conditions; (aiii) there is a lack of consistency in the definitions used to describe and report some transfusion reactions, their severity and their likelihood of being related to transfusion; and (aiv) it is difficult to assess the imputability of a particular BC given to a patient who has previously received many BCs over a relatively short period of time. When compiling all available information published so far, it appears that TAHs can be analysed using different approaches: (bi) their pathophysiological nature; (bii) their severity; (biii) the onset scheme; (biv) a quality assessment (preventable or non-preventable); (bv) their impact on ongoing therapy. Moreover, TAHs can be reported either in a non-integrative or in an integrative way; in the latter case, presentation may also differ when issued by a blood establishment or a treating ward. At some point, a recapitulative document would be useful to gain a better understanding of TAHs in order to decrease their occurrence and severity and allow decision makers to determine action plans: this is what this review attempts to make. This review attempts to merge the different aspects, with a focus on the hospital side, i.e., how the most frequent TAHs can be avoided or mitigated., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Acute traumatic coagulopathy (ATC) is an acute and endogenous mechanism triggered by the association of trauma and hemorrhage. Several animal models have been developed, but some major biases have not yet been identified. Our aim was to develop a robust and clinically relevant murine model to study this condition. Anesthetized adult Sprague Dawley rats were randomized into 4 groups: C, control; T, trauma; H, hemorrhage; TH, trauma and hemorrhage (n = 7 each). Trauma consisted of laparotomy associated with four-limb and splenic fractures. Clinical variables, ionograms, arterial and hemostasis blood tests were compared at 0 and 90 min. ATC and un-compensated shock were observed in group TH. In this group, the rise in prothrombin time and activated partial thromboplastin was 29 and 40%, respectively. Shock markers, compensation mechanisms and coagulation pathways were all consistent with human pathophysiology. The absence of confounding factors, such as trauma-related bleeding or dilution due to trans-capillary refill was verified. This ethic, cost effective and bias-controlled model reproduced the specific and endogenous mechanism of ATC and will allow to identify potential targets for therapeutics in case of trauma-related hemorrhage.

Background and Objectives: A postauthorization safety study was performed between 2009 and 2012 to describe the use of Clottafact ® in acquired fibrinogen deficiency in real-life medical practice in France., Materials and Methods: One hundred and fifty patients were planned for 28 days of prospective follow-up after infusion. The analysis of this observational study was descriptive and performed according to the type of treatment (curative or preventive) and the origin of the bleed., Results: One hundred and fifty-six patients (16-87 years) were included in 13 centres and treated in five different medical bleeding situations: postpartum (59), other gynaecological/obstetrical (6), trauma (34), liver (13), cardiovascular (23) and other various bleeding situations (21). The mean follow-up time was 18·9 ± 12·3 days. Two patients presented adverse drug reactions: one a pulmonary embolism and the other a four-site venous thromboembolic episode. All were serious with a dubious causal relationship with the study treatment. Efficacy data were collected as a secondary objective. In 150 patients receiving curative treatment, 117 of 159 infusions (73·6%) were considered as successful by the investigators, 35 as moderate (22%) and seven as no response (4·4%)., Conclusion: The Clottafact ® safety profile observed during the study matched the known profile of fibrinogen during use., (© 2017 International Society of Blood Transfusion.)

Using the French Hemovigilance Network database from 2007 to 2013, we provide information on demographics, incidence, and risk factors of reported transfusion-related acute lung injury (TRALI) and possible TRALI, analyze TRALI mitigation efforts for fresh frozen plasma and platelet concentrates, and consider the impact of platelet additive solutions on TRALI incidence. We applied the Toronto consensus conference definitions for TRALI and possible TRALI. Two TRALI subgroups were considered: "antibody positive" when a donor has human leukocyte antigen (class I or II) and/or human neutrophil antigen antibodies and the recipient has cognate antigen, and "antibody negative" when immunological investigation is negative or not done. The analysis targeted 378 cases, divided into antibody-positive TRALI (n=75), antibody-negative TRALI (n=100), and possible TRALI (n=203). TRALI patients were younger and received more blood components than the general population of transfused patients. Moreover, we identified the following clinical conditions where patients seemed to be at higher risk to develop TRALI: postpartum hemorrhage, acute myeloid leukemia, liver transplantation, allogeneic and autologous hematopoietic stem cells transplantation, polytrauma, and thrombotic microangiopathy. Policy measures intended to reduce antibody-positive TRALI were found effective for apheresis platelet concentrates and fresh frozen plasma but not for whole blood-derived platelet concentrates. The use of platelet additive solutions was associated with a significant reduction in the incidence of TRALI following transfusion of buffy coat-derived platelet concentrates but not following transfusion of apheresis platelets. Our data reinforce the concept that possible TRALI and TRALI, as defined in the Canadian consensus conference, share many characteristics. No specific policy measures are currently directed at mitigation of possible TRALI despite its impact on transfusion safety. Despite TRALI mitigation measures, the overall incidence of TRALI cases reported to the French Hemovigilance system was not significantly reduced. Therefore, additional research is needed to reduce, if not eradicate, all TRALI categories., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Hospital-acquired anemia is common, especially in the most critically ill patients. It may be associated with poor patient outcomes. It may result from increased blood loss, impaired red cell production or reduced red cell life span. Multiple associated factors may contribute simultaneously or sequentially to the decrease in hemoglobin level. Some of them are related to the underlying disease and others are iatrogenic. Clinicians should be aware of the importance and consequences of iatrogenic anemia caused by diagnostic blood sampling. Strategies and measures to minimize iatrogenic blood loss should be prioritized. They may reduce the risk of developing anemia and then red blood cells transfusion requirement., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Objective: The most common complications of hyperbaric oxygen treatment (HBOT) are related to pressure changes on gas-containing cavities. Therefore, inability to auto-inflate the middle ear may result in transient or permanent hearing loss. However, it seems that middle ear barotrauma (MEBt) does not develop more often in mechanically ventilated patients than in ambulatory patients. This might be explained by deep sedation of these patients. Therefore, the aim of this study was to determine whether anaesthesia and/or neuromuscular blockade can influence Eustachian tube (ET) function., Methods: Forty patients who were undergoing surgery under general anaesthesia were enrolled in this prospective study. ET function was evaluated by tympanography performed three times: before induction of general anaesthesia (baseline), after induction with sufentanyl/propofol and after full blockade was achieved with a long-acting neuromuscular blocking agent., Results: There were no differences in ear volume (P = 0.19) and ear pressure (P = 0.07). There was a significant variation in compliance on tympanography after the induction of general anaesthesia (P = 0.009). Compared to the baseline, this variation was characterized by an increase after induction of anaesthesia (24 ± 7.13%, P 〈 0.01) and neuromuscular blockade (23 ± 8.9%, P 〈 0.05). The difference between after induction and after neuromuscular blockade was not statistically significant (P = 0.13)., Discussion: The findings of this trial suggest that the administration of hypnotic drugs associated with opioids improves ET compliance. Therefore it may have favourable prophylactic effects on MEBt in ventilated intensive care unit patients scheduled for HBOT.

Background: 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., Methods: 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., Results: 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., Conclusions: 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.

Hydrostatic pulmonary edema is a frequent and severe complication of blood transfusion. Recent epidemiological studies open the way for a better prevention of Transfusion-Associated Circulatory Overload. Preventive measures rely solely on the medical and nursing staff. Mitigation strategies include a careful identification of patients and conditions at-risk, a single-unit transfusion policy in patients with chronic anemia, the use of slow infusion rates, the careful monitoring of patient vital signs (particularly systemic arterial blood pressure). Peritransfusion IV diuretics use is likely to be helpful, although optimal prescribing patterns have not been defined., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

It is well known that immersion pulmonary edema can be life-threatening for divers using a self-contained underwater breathing apparatus (scuba). Swimming-induced pulmonary edema in otherwise healthy individuals is not an object of dispute but its real severity is not well known and is probably underestimated. We report two cases of life-threatening acute respiratory distress while swimming and snorkeling, one of which is well documented for swimming-induced pulmonary edema. The interest of these case reports lies in the suddenness of these life-threatening events. Such accidents can mimic a loss of consciousness due to cardiac dysrhythmia and lead to drowning. In the case of swimming-induced pulmonary edema, the prognosis is far better than for a cardiac disorder, but it is also dependent on the efficiency of the supervision. Swimmers, divers, race organizers and supervising physicians should be given knowledge of this pathology and its potentially acute occurrence. Adequate organizational dispositions are mandatory to prevent swimming-induced pulmonary edema-related deaths.

ICU acquired neuromyopathy (IANM) is the most frequent neurological pathology observed in ICU. Nerve and muscle defects are merged with neuromuscular junction abnormalities. Its physiopathology is complex. The aim is probably the redistribution of nutriments and metabolism towards defense against sepsis. The main risk factors are sepsis, its severity and its duration of evolution. IANM is usually diagnosed in view of difficulties in weaning from mechanical ventilation, but electrophysiology may allow an earlier diagnosis. There is no curative therapy, but early treatment of sepsis, glycemic control as well as early physiotherapy may decrease its incidence. The outcomes of IANM are an increase in morbi-mortality and possibly long-lasting neuromuscular abnormalities as far as tetraplegia., (Copyright © 2013 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.)

Background: The clinical equivalence of plasma treated to reduce pathogen transmission and untreated plasma has not been extensively studied. A clinical trial was conducted in liver transplant recipients to compare the efficacy of three plasmas., Study Design and Methods: A randomized, equivalence, blinded trial was performed in four French liver transplantation centers. The three studied (fresh-frozen) plasmas were quarantine (Q-FFP), methylene blue (MB-FFP), and solvent/detergent (S/D-FFP) plasmas. The primary outcome was the volume of plasma transfused during transplantation. Secondary outcomes included intraoperative blood loss, hemostasis variables corrections, and adverse events., Results: One-hundred patients were randomly assigned in the MB-FFP, 96 in the S/D-FFP, and 97 in the Q-FFP groups, respectively. The median volumes of plasma transfused were 2254, 1905, and 1798 mL with MB-FFP, S/D-FFP, and Q-FFP, respectively. The three plasmas were not equivalent. MB-FFP was not equivalent to the two other plasmas, but S/D-FFP and Q-FFP were equivalent. The median numbers of transfused plasma units were 10, 10, and 8 units with MB-FFP, S/D-FFP, and Q-FFP, respectively. Adjustment on bleeding risk factors diminished the difference between groups: the excess plasma volume transfused with MB-FFP compared to Q-FFP was reduced from 24% to 14%. Blood loss and coagulation factors corrections were not significantly different between the three arms., Conclusion: Compared to both Q-FFP and S/D-FFP, use of MB-FFP was associated with a moderate increase in volume transfused, partly explained by a difference in unit volume and bleeding risk factors. Q-FFP was associated with fewer units transfused than either S/D-FFP or MB-FFP., (© 2012 American Association of Blood Banks.)

Patients with end-stage liver disease have complex alterations that involve all components of hemostasis, with changes both in prohemostatic and in antihemostatic pathways. Routine haemostasis tests such as prothrombin time and platelet count are unable to reflect a bleeding tendency. Bleeding complications are much less related to abnormal hemostasis than previously thought, with portal hypertension playing a more critical role. Systematic prophylactic measures based upon the use of fresh frozen plasma and/or platelet concentrates to improve or correct the abnormalities of the routine coagulation tests are most often inappropriate and may occasionally be deleterious., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

According to the World Health Organization, traumatic injuries worldwide are responsible for over 5 million deaths annually. Post-traumatic bleeding caused by traumatic injury-associated coagulopathy is the leading cause of potentially preventable death among trauma patients. Despite these facts, awareness of this problem is insufficient and treatment options are often unclear. The STOP the Bleeding Campaign therefore aims to increase awareness of the phenomenon of post-traumatic coagulopathy and its appropriate management by publishing European guidelines for the management of the bleeding trauma patient, by promoting and monitoring the implementation of these guidelines and by preparing promotional and educational material, organising activities and developing health quality management tools. The campaign aims to reduce the number of patients who die within 24 hours after arrival in the hospital due to exsanguination by a minimum of 20% within the next 5 years.

Introduction: Evidence-based recommendations are needed to guide the acute management of the bleeding trauma patient. When these recommendations are implemented patient outcomes may be improved., Methods: The multidisciplinary Task Force for Advanced Bleeding Care in Trauma was formed in 2005 with the aim of developing a guideline for the management of bleeding following severe injury. This document represents an updated version of the guideline published by the group in 2007 and updated in 2010. Recommendations were formulated using a nominal group process, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence and based on a systematic review of published literature., Results: Key changes encompassed in this version of the guideline include new recommendations on the appropriate use of vasopressors and inotropic agents, and reflect an awareness of the growing number of patients in the population at large treated with antiplatelet agents and/or oral anticoagulants. The current guideline also includes recommendations and a discussion of thromboprophylactic strategies for all patients following traumatic injury. The most significant addition is a new section that discusses the need for every institution to develop, implement and adhere to an evidence-based clinical protocol to manage traumatically injured patients. The remaining recommendations have been re-evaluated and graded based on literature published since the last edition of the guideline. Consideration was also given to changes in clinical practice that have taken place during this time period as a result of both new evidence and changes in the general availability of relevant agents and technologies., Conclusions: A comprehensive, multidisciplinary approach to trauma care and mechanisms with which to ensure that established protocols are consistently implemented will ensure a uniform and high standard of care across Europe and beyond.

"Transfusion-related acute lung injury" (TRALI) is a post-transfusion lesional pulmonary edema, potentially severe, better defined since the conference of Toronto in 2004. The incidence of TRALI reported in France remains low in part because of its ignorance by physicians. The objective of our study was to evaluate retrospectively transfusion accidents with respiratory complications that occurred in Nancy University Hospital and reported to the haemovigilance between 1996 and 2006, from the software "Traceline" listing all the blood transfusion complications from signs observed. The analysis of the files has been performed by applying rigorously diagnostic criteria of Toronto. Forty-one cases of respiratory complications were found in 34,573 blood products. Ten cases of TRALI were diagnosed while only one case had been reported to the haemovigilance. The remaining nine cases were previously labeled transfusion-associated circulatory overload (TACO). No cases of TRALI have been identified in the ICU. Our work can find an incidence of TRALI 10 times greater than previously reported. Ignorance of TRALI and the lack of consensus definition before 2004 are not sufficient to explain these results. This study demonstrates the potential interest of database and computerized declaration system based on the symptoms observed. It highlights the vulnerability of the current haemovigilance too dependent on a single medical observer. Although TRALI are recognized as serious complications, sometimes requiring resuscitative care, our work was not isolated severe TRALI in ICU. Physician awareness of TRALI to the identification and to the declaration, including ICU should be continued. Finally, the diagnostic criteria for TRALI must be adapted to the ICU., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Background: Postpartum hemorrhage is the leading cause of maternal death worldwide. Recent data from trauma patients and patients with hemorrhagic shock have suggested that an increased fresh frozen plasma:red blood cell (FFP:RBC) ratio may be of benefit in massive bleeding. We addressed this issue in cases of severe postpartum hemorrhage., Methods: We reviewed data from all patients diagnosed with severe postpartum hemorrhage during a 4-year period (2006-2009). Patients who were treated with sulprostone and required transfusion within 6 hours of delivery were included in the study and were divided into 2 groups according to their response to sulprostone: bleeding controlled with sulprostone alone (sulprostone group) and bleeding requiring an additional advanced interventional procedure including arterial angiographic embolization and/or surgical procedures (arterial ligation, B-Lynch suture, or hysterectomy; intervention group). The requirement or no requirement for advanced procedures constituted the primary end point of the study. Propensity scoring was used to assess the effect of a high FFP:RBC ratio on bleeding control., Results: Among 12,226 deliveries during the study period, 142 (1.1%) were complicated by severe postpartum hemorrhage. Bleeding was controlled with sulprostone alone in 90 patients (63%). Advanced interventional procedures were required for 52 patients (37%). Forty-one patients were transfused with both RBCs and FFP. The FFP:RBC ratio increased over the study period (P < 0.001), from 1:1.8 at the start to 1:1.1 at the end of the study period. After propensity score modeling (inverse probability of treatment weighting), a high FFP:RBC ratio was associated with lower odds for advanced interventional procedures (odds ratio [95% confidence interval], 1.25 [1.07-1.47]; P = 0.008). There were no deaths, severe organ dysfunction, or other complications as a consequence of severe postpartum hemorrhage., Conclusions: In this retrospective study, a higher FFP:RBC ratio was associated with a lower requirement for advanced interventional procedures in the setting of postpartum hemorrhage. The benefits of transfusion using a higher FFP:RBC ratio should be confirmed by randomized-controlled trials.

Recent changes in plasma transfusion practices for severe hemorrhage are largely related to the recognition of an early endogenous coagulopathy associated with traumatic injury. Observational and mostly retrospective data suggest improved survival rates with high-dose plasma therapy, up to a 1:1 ratio of fresh frozen plasma to packed red blood cells, but the quality of evidence is limited. Putting it into practice raises many issues (early identification of patients at risk of massive bleeding, extrapolation to non-trauma settings, alternative or adjunctive treatments, among others) that are discussed in this brief review., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

A working group of the French National Hemovigilance Committee has been in charge of heightening awareness of Transfusion-Associated Circulatory Overload (TACO) among physicians and nurses. This multidisciplinary group has produced the present document that focuses on epidemiological data provided by the French haemovigilance network, physiopathology, diagnosis, treatment and specific actions that could prevent or minimize the risk of TACO., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Bacillus cereus is a well-known cause of foodborne disease usually of benign course. Here, we present the case of a 15-year-old boy who developed reversible fulminant liver failure associated with rhabdomyolysis after pasta consumption. Suspecting B. cereus as the aetiological agent may prevent unnecessary liver transplantation., (© 2012 SGM)

Background: Transfusion-related acute lung injury (TRALI) is a major cause of transfusion-related mortality and morbidity. Epidemiologic studies using data from national transfusion schemes can help achieve a better understanding of TRALI incidence., Study Design and Methods: A multidisciplinary working group analyzed TRALI cases extracted from the French Hemovigilance Network Database (2007-2008). All notified cases were reviewed for diagnosis. Those meeting the Canadian Consensus Conference criteria for TRALI were classified according to imputability to transfusion and clinical severity. Patient data (clinical characteristics, number and types of products transfused, and serology results) were obtained., Results: There were 62 TRALI cases and 23 possible TRALI cases during the 2-year period. An immune-mediated mechanism was identified in 30 of 50 TRALI cases with complete serology. TRALI was considered to be the cause of death in 7.1% of patients and might have contributed to death in an additional 9.4% of TRALI or possible TRALI patients. Occurrence ranked high in obstetrics (15%), after surgery (34%), and in hematologic malignancies (21%). Single-donor high-plasma-volume components were involved in half of the cases where the implicated blood product could be determined and carried the highest risk per component (1:31,000 for single-donor fresh-frozen plasma units and apheresis platelet [PLT] concentrates, and 1:173,000 for red blood cells). No incident could be definitively related to the transfusion of solvent/detergent-treated pooled plasma (>200,000 units transfused), nor to pooled PLT concentrates., Conclusion: The proportion of TRALI cases related to plasma-rich components was lower than previously described., (© 2011 American Association of Blood Banks.)

Coagulopathy during massive haemorrhage increases morbidity and mortality rates. The modalities of treatment by transfusion of fresh frozen plasma (FFP) are a matter of debate. According to most clinical practice guidelines, FFP administration is driven by coagulation tests but, in cases of massive transfusion, patient management may be delayed whilst awaiting results and thawing FFP. Several retrospective cohort studies of military or civilian multiple trauma casualties requiring massive transfusion (>10 red blood cells (RBC) within 24h) have suggested that early use of FFP and high FFP:RBC ratios (approaching 1) might improve survival and lessen morbidity. However, the methodology of these studies is suboptimal. They are subject, in particular, to survival bias. Massive FFP transfusions can also lead to an enhanced incidence of transfusion-related acute lung injury (TRALI), acute respiratory distress syndrome (ARDS), and multi-organ failure. At the present time, it is clear that FFP transfusion should be initiated early with a high FFP:RBC ratio in massive bleeding associated with haemostatic abnormalities such as multiple trauma. This does not imply that such a recommendation can be extended to the correction of high blood loss in other situations such as scheduled surgery. Actually, very few patients are likely to derive benefit from a 1/1 FFP:RBC transfusion strategy. They are chiefly multiple trauma victims with haemorrhagic shock and cases of ruptured abdominal aortic aneurysm. In other patients, in order to minimize risks and costs, a more parsimonious FFP use policy remains the best option until evidence for the benefit of 1/1 FFP:RBC is demonstrated., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Previously undiagnosed anaemia is common in elective orthopaedic surgical patients and is associated with increased likelihood of blood transfusion and increased perioperative morbidity and mortality. A standardized approach for the detection, evaluation, and management of anaemia in this setting has been identified as an unmet medical need. A multidisciplinary panel of physicians was convened by the Network for Advancement of Transfusion Alternatives (NATA) with the aim of developing practice guidelines for the detection, evaluation, and management of preoperative anaemia in elective orthopaedic surgery. A systematic literature review and critical evaluation of the evidence was performed, and recommendations were formulated according to the method proposed by the Grades of Recommendation Assessment, Development and Evaluation (GRADE) Working Group. We recommend that elective orthopaedic surgical patients have a haemoglobin (Hb) level determination 28 days before the scheduled surgical procedure if possible (Grade 1C). We suggest that the patient's target Hb before elective surgery be within the normal range, according to the World Health Organization criteria (Grade 2C). We recommend further laboratory testing to evaluate anaemia for nutritional deficiencies, chronic renal insufficiency, and/or chronic inflammatory disease (Grade 1C). We recommend that nutritional deficiencies be treated (Grade 1C). We suggest that erythropoiesis-stimulating agents be used for anaemic patients in whom nutritional deficiencies have been ruled out, corrected, or both (Grade 2A). Anaemia should be viewed as a serious and treatable medical condition, rather than simply an abnormal laboratory value. Implementation of anaemia management in the elective orthopaedic surgery setting will improve patient outcomes.

Pulmonary oedema after transfusion of blood products may be hydrostatic (transfusion-associated circulatory overload [taco]) or exsudative (transfusion-related acute lung injury [trali]). Both conditions have been recognized as major hazards to transfusion recipients. Risk characterization is necessary to improve safety and to monitor trends in the national blood transfusion system. A collaborative multidisciplinary working group of the French National Hemovigilance Committee has proposed an analysis framework for case definitions and classification. The method relies on internationally used definitions and is adapted to the codification procedures used in the french transfusion incident reports electronic data management., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Background: The optimal effective dose of epidural morphine that provides postoperative analgesia after caesarean section with minimal side effects remains debated., Aims: We performed a systematic review to assess the analgesic efficacy and the incidence of adverse effects of epidural morphine after caesarean section compared to systemic analgesia with opioids., Methods: We searched Medline, Embase and Cochrane Collaboration Library databases. Studies were evaluated with the Modified Oxford Scale. Prospective randomized studies comparing analgesic efficacy and/or adverse effects of a single epidural morphine administration versus systemic opioids after elective caesarean section were included., Results: Ten studies (n=431) were selected. Epidural morphine increases the time until the first request for a rescue analgesic (Emax, 29.7 h; 95% confidence interval, 25.2-33.9) and decreases pain scores and postoperative morphine request during the first 24 h compared to systemic opioid analgesia. However, epidural morphine increases the incidence of pruritus (relative risk, 2.7; 95% CI, 2.1-3.6) and nausea (relative risk, 2.0; 95% CI, 1.2-3.3)., Conclusions: A single bolus of epidural morphine provides better analgesia than parenteral opioids but with an effect limited to the first postoperative day after caesarean section and with an increase in morphine side effects., (Copyright © 2010 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.)

Objective: To evaluate in which anatomical layer (above the fascia or below the fascia) continuous wound infusion of local anesthetic, combined with nonsteroidal antiinflammatory drugs, through a multiorifice catheter has the best effectiveness during the first 48 hours on postoperative pain intensity after elective cesarean delivery., Methods: Fifty-six women undergoing elective cesarean delivery under spinal anesthesia were randomly allocated to receive 48-hour continuous wound infusion either above the fascia or below the fascia using ropivacaine and ketoprofene through a multiholed wound catheter. No other systemic analgesics were used, except for rescue patient-controlled intravenous morphine. Evaluation by a blinded investigator included visual analog scale scores at rest and at movement, morphine consumption, patient satisfaction, residual pain at 1 and 6 months, and undesirable side effects., Results: Continuous wound infusion below the fascia resulted in significantly reduced pain at rest and total postoperative morphine consumption (15.7 mg, 95% confidence interval 9.7-20.7 mg) compared with wound administration above the fascia (26.4 mg, 95% confidence interval 18.1-34.7). No undesirable side effects or residual pain requiring treatment were recorded in both groups, whereas analgesia and satisfaction were excellent., Conclusion: After cesarean delivery, continuous wound infusion over 48 hours with ropivacaine and ketoprofene through a multiholed wound catheter inserted below the fascia results in better analgesia when compared with administration above the fascia., Clinical Trial Registration: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01160913., Level of Evidence: I.

This article provides an overview of the scientific evidence regarding the efficacy and safety of antifibrinolytic agents and desmopressin to reduce surgical blood loss. The synthetic derivatives of lysine are the only antifibrinolytics available in clinical practice since the withdrawal of aprotinin. There is evidence that the prophylactic use of lysine analogues is efficacious in reducing perioperative blood loss in cardiac and major orthopaedic surgery. The impact on exposure to blood transfusion is, however, variable. There is no evidence at present that they improve the overall outcome. Lysine analogues appear to be well tolerated in coronary artery bypass surgery, but less is known regarding their risk-benefit profile in special patient groups. Further studies are needed to elucidate the best compromise between dosing regimen, efficacy and safety in various clinical settings. Desmopressin may reduce excessive bleeding and transfusion requirements in some specific patient populations with acquired platelet dysfunction, but this needs to be validated in future studies.

Background: After a vitamin K antagonist (VKA) overdose, 1-2 mg of oral vitamin K can lower the International Normalized Ratio (INR) to the therapeutic range., Objective: To establish whether oral vitamin K can substitute for heparin bridging and decrease the INR to < or = 1.5 before elective surgery., Methods: Patients on long-term VKAs were randomized either to heparin bridging after the last VKA dose on day -5 before surgery (group H) or to VKA treatment until day -2, followed by 1 mg of oral vitamin K on the day before surgery (group K). Blood clotting variables were assessed on days -5/-2, 1 and 0, and postoperatively. If the target INR was not achieved 2 h before incision, surgery was deferred or performed after injection of prothrombin complex concentrate (PCC)., Results: In 30 of 94 included patients, baseline INR was outside the chosen range (18, INR < 2; 12, INR > 3.5), leaving 34 eligible patients in group H and 30 in group K. The groups were balanced in terms of body mass index, VKA treatment duration and indication, scheduled surgery, preoperative and postoperative hemoglobin, and blood loss. The INR was significantly higher in group K on days -1 and 0 than in group H. An INR < or = 1.5 was not achieved in 20 group K patients (66%). Surgery was postponed or performed after PCC injection in 12 of these 20 patients., Conclusions: Oral vitamin K (1 mg) cannot substitute for heparin bridging before surgery. In addition, one-third of patients on VKAs were exposed to a risk of bleeding (overdose) or thrombosis (underdose), thus highlighting the need for new oral anticoagulants.

Introduction: Evidence-based recommendations are needed to guide the acute management of the bleeding trauma patient, which when implemented may improve patient outcomes., Methods: The multidisciplinary Task Force for Advanced Bleeding Care in Trauma was formed in 2005 with the aim of developing a guideline for the management of bleeding following severe injury. This document presents an updated version of the guideline published by the group in 2007. Recommendations were formulated using a nominal group process, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence and based on a systematic review of published literature., Results: Key changes encompassed in this version of the guideline include new recommendations on coagulation support and monitoring and the appropriate use of local haemostatic measures, tourniquets, calcium and desmopressin in the bleeding trauma patient. The remaining recommendations have been reevaluated and graded based on literature published since the last edition of the guideline. Consideration was also given to changes in clinical practice that have taken place during this time period as a result of both new evidence and changes in the general availability of relevant agents and technologies., Conclusions: This guideline provides an evidence-based multidisciplinary approach to the management of critically injured bleeding trauma patients.

Hemiplegic migraine is a condition associated with vascular alteration of the central nervous system and transient neurologic deficits. Permanent morphine-induced motor dysfunction has been reported after spinal ischemia. We report a persisting central neurological deficit after single-dose spinal administration of 400 microg of morphine in a patient with no previous neurological condition. Hemiplegic migraine was thought to be present when the patient emerged from anesthesia. Weakness in the left quadriceps and saddle anesthesia of the perineum and urinary retention of central origin remained present 3 yr later. Over the 3 postoperative years, the patient was admitted to a neurological unit 5 times because of acute headache associated with complete left-sided hemiplegia. These symptoms resolved within 24 h of onset. Hemiplegic migraine was thought to be the most likely diagnosis of these recurrent attacks. We hypothesize that the patient's persistent deficits were caused by a combination of spinal morphine and spinal cord vascular dysfunction associated with hemiplegic migraine.

Digestive surgery in cirrhotic patients has long been limited to the treatment of disorders related to the liver disease (portal hypertension, hepatocellular carcinoma and umbilical hernia). The improvement in cirrhotic patient management has allowed an increase in surgical procedures for extrahepatic indications. The aim of this study was to evaluate the operative risks of such surgical procedures. Extrahepatic surgery in cirrhotic patients is associated with high mortality and morbidity. Emergency surgery, gastrointestinal tract opening (esophagus, stomach and colon), <30 g/L serum albumin, transaminase levels more than three times the upper limit of normal, ascites, and intraoperative transfusions are the main risk factors for postoperative death. In Child A patients, the operative risk of elective surgery is moderate and surgical indications are not altered by the presence of cirrhosis. The laparoscopic approach should be recommended because of the potentially lower morbidity. In Child C patients, operative mortality is often higher than 40%; surgical indications must remain exceptional and non operative management has to be preferred. In Child B patients, preoperative improvement of liver function is mandatory for lower risk surgery.