Adverse events of iron and/or erythropoiesis-stimulating agent therapy in preoperatively anemic elective surgery patients: a systematic review.

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.

Lack of Cost-Effectiveness of Preoperative Erythropoiesis-Stimulating Agents and/or Iron Therapy in Anaemic, Elective Surgery Patients: A Systematic Review and Updated Analysis.

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.

Effectiveness of Iron Supplementation With or Without Erythropoiesis-Stimulating Agents on Red Blood Cell Utilization in Patients With Preoperative Anaemia Undergoing Elective Surgery: A Systematic Review and Meta-Analysis.

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).

Is there an optimal trade-off between anaemia and red blood cell transfusion in surgical critically ill patients after oncologic surgery?

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).

Effects of intraoperative high versus low inspiratory oxygen fraction (FiO2) on patient's outcome: A systematic review of evidence from the last 20 years.

Despite numerous studies, controversies about the best intraoperative FiO2 remain. In 2016, the World Health Organization (WHO) recommended that adult patients undergoing general anaesthesia should be ventilated intraoperatively with an 80% FiO2 to reduce surgical site infection (SSI). However, several data suggest that hyperoxia could have adverse effects. In order to determine the potential effect of FiO2 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 FiO2. 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 FiO2 during general anaesthesia. There was also no difference in the incidence of SSI depending of intraoperative FiO2 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 FiO2. On the opposite, some data from follow-up analyses and registry studies suggested a possible negative effect of high intraoperative FiO2 on long-term outcomes. In conclusion, the systematic administration of a high intraoperative FiO2 in order to decrease SSI or improve other perioperative outcomes seems unjustified in the light of the evidence currently available in the literature.

New considerations on pathways involved in acute traumatic coagulopathy: the thrombin generation paradox.

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 R2: 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.

Risk factors for immersion pulmonary edema in recreational scuba divers: a case-control study.

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.

Patient Blood Management: Recommendations From the 2018 Frankfurt Consensus Conference.

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.

Patient blood management: recommendations rrom the 2018 Frankfurt consensus conference

What is the current evidence base for patient blood management (PBM) in adults, and what international clinical recommendations can be derived for preoperative anemia, red blood cell transfusion thresholds, and PBM implementation strategies? Diagnosis and management of preoperative anemia is crucial, and iron-deficient anemia should be treated with iron supplementation. Red blood cell transfusion thresholds for critically ill, clinically stable patients (hemoglobin concentration <7 g/dL), patients undergoing cardiac surgery (hemoglobin concentration <7.5 g/dL), patients with hip fractures and cardiovascular disease or risk factors (hemoglobin concentration <8 g/dL), and hemodynamically stable patients with acute gastrointestinal bleeding (hemoglobin concentration 7-8 g/dL) are relatively well defined, although the quality of evidence is moderate to low. Further high-quality research to support PBM is required for a range of clinical scenarios and implementation of PBM programs.

Platelet storage duration and its clinical and transfusion outcomes: a systematic review.

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 place of fibrinogen concentrates in the management of perioperative bleeding: A position paper from the Francophone Working Group on Perioperative Haemostasis (GIHP).

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.

Analysis of Transfusion-Related Acute Lung Injury and Possible Transfusion-Related Acute Lung Injury Reported to the French Hemovigilance Network From 2007 to 2013.

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.

The effect of general anaesthesia and neuromuscular blockade on Eustachian tube compliance: a prospective study.

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.

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

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.

The STOP the Bleeding Campaign.

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.

Management of bleeding and coagulopathy following major trauma: an updated European guideline.

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.

An observational study of the fresh frozen plasma: red blood cell ratio in postpartum hemorrhage.

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.

Plasma transfusion in liver transplantation: a randomized, double-blind, multicenter clinical comparison of three virally secured plasmas.

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.