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BACKGROUND: Thromboelastography/metry (TEG(R); Haemoscope, Niles, IL/ROTEM(R); Tem International GmbH, Munich, Germany) is increasingly used to guide transfusion therapy. This study investigated the diagnostic performance and therapeutic consequence of using kaolin-activated whole blood compared with a panel of specific TEM(R)-reagents to distinguish: dilutional coagulopathy, thrombocytopenia, hyperfibrinolysis, and heparinization. METHODS: Blood was drawn from 11 healthy volunteers. Dilutional coagulopathy was generated by 50% dilution with hydroxyethyl starch 130/0.4 whereas thrombocytopenia (mean platelet count 20 x10/l) was induced using a validated model. Hyperfibrinolysis and heparin contamination were generated by tissue plasminogen activator 2 nM and unfractionated heparin 0.1U/ml, respectively. Coagulation tests were run on ROTEM(R) delta. RESULTS: Kaolin-activated whole blood showed no differences between dilutional coagulopathy and thrombocytopenia (mean clotting time 450 s vs. 516 s, [alpha]-angle 47.1° vs. 41.5°, maximum clot firmness 35.0 mm vs. 34.2 mm, all P values >=0.14). Hyperfibrinolysis specifically disclosed an increased maximum lysis (median: 100%, all P values less than 0.001), and heparin induced a distinctly prolonged clotting time (2283 s, all P values less than 0.02). The coagulopathies were readily distinguishable using a panel of TEM-reagents. In particular, dilutional coagulopathy was separated from thrombocytopenia using FIBTEM (maximum clot firmness 1.9 mm vs. 11.2 mm, P < 0.001). The run time of analysis to achieve diagnostic data was shorter applying a panel of TEM-reagents. A transfusion algorithm based on kaolin suggested platelets in case of dilutional coagulopathy, whereas an algorithm applying TEM-reagents suggested fibrinogen. CONCLUSION: Monoanalysis with kaolin was unable to distinguish coagulopathies caused by dilution from that of thrombocytopenia. Algorithms based on the use of kaolin may lead to unnecessary transfusion with platelets, whereas the application of TEM-reagents may result in goal-directed fibrinogen substitution. [ABSTRACT FROM AUTHOR]

Importance: Early administration of supplemental oxygen for all severely injured trauma patients is recommended, but liberal oxygen treatment has been associated with increased risk of death and respiratory complications., Objective: To determine whether an early 8-hour restrictive oxygen strategy compared with a liberal oxygen strategy in adult trauma patients would reduce death and/or major respiratory complications., Design, Setting, and Participants: This randomized controlled trial enrolled adult trauma patients transferred directly to hospitals, triggering a full trauma team activation with an anticipated hospital stay of a minimum of 24 hours from December 7, 2021, to September 12, 2023. This multicenter trial was conducted at 15 prehospital bases and 5 major trauma centers in Denmark, the Netherlands, and Switzerland. The 30-day follow-up period ended on October 12, 2023. The primary outcome was assessed by medical specialists in anesthesia and intensive care medicine blinded to the randomization., Interventions: In the prehospital setting or on trauma center admission, patients were randomly assigned 1:1 to a restrictive oxygen strategy (arterial oxygen saturation target of 94%) (n = 733) or liberal oxygen strategy (12-15 L of oxygen per minute or fraction of inspired oxygen of 0.6-1.0) (n = 724) for 8 hours., Main Outcomes and Measures: The primary outcome was a composite of death and/or major respiratory complications within 30 days. The 2 key secondary outcomes, death and major respiratory complications within 30 days, were assessed individually., Results: Among 1979 randomized patients, 1508 completed the trial (median [IQR] age, 50 [31-65] years; 73% male; and median Injury Severity Score was 14 [9-22]). Death and/or major respiratory complications within 30 days occurred in 118 of 733 patients (16.1%) in the restrictive oxygen group and 121 of 724 patients (16.7%) in the liberal oxygen group (odds ratio, 1.01 [95% CI, 0.75 to 1.37]; P = .94; absolute difference, 0.56 percentage points [95% CI, -2.70 to 3.82]). No significant differences were found between groups for each component of the composite outcome. Adverse and serious adverse events were similar across groups, with the exception of atelectasis, which was less common in the restrictive oxygen group compared with the liberal oxygen group (27.6% vs 34.7%, respectively)., Conclusions and Relevance: In adult trauma patients, an early restrictive oxygen strategy compared with a liberal oxygen strategy initiated in the prehospital setting or on trauma center admission for 8 hours did not significantly reduce death and/or major respiratory complications within 30 days., Trial Registration: ClinicalTrials.gov Identifier: NCT05146700.

Background: Anticoagulation is essential for the treatment and prevention of thromboembolic events. Current guidelines recommend direct oral anticoagulants (DOACs) over vitamin K antagonists in DOAC-eligible patients. The major complication of anticoagulation is serious or life-threatening haemorrhage, which may necessitate prompt haemostatic intervention. Reversal of DOACs may also be required for patients in need of urgent invasive procedures. This guideline from the European Society of Anaesthesiology and Intensive Care (ESAIC) aims to provide evidence-based recommendations and suggestions on how to manage patients on DOACs undergoing urgent or emergency procedures including the treatment of DOAC-induced bleeding., Design: A systematic literature search was performed, examining four drug comparators (dabigatran, rivaroxaban, apixaban, edoxaban) and clinical scenarios ranging from planned to emergency surgery with the outcomes of mortality, haematoma growth and thromboembolic complications. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) methodology was used to assess the methodological quality of the included studies. Consensus on the wording of the recommendations was achieved by a Delphi process., Results: So far, no results from prospective randomised trials comparing two active comparators (e.g. a direct reversal agent and an unspecific haemostatic agent such as prothrombin complex concentrate: PCC) have been published yet and the majority of publications were uncontrolled and observational studies. Thus, the certainty of evidence was assessed to be either low or very low (GRADE C). Thirty-five recommendations and clinical practice statements were developed. During the Delphi process, strong consensus (>90% agreement) was achieved in 97.1% of recommendations and consensus (75 to 90% agreement) in 2.9%., Discussion: DOAC-specific coagulation monitoring may help in patients at risk for elevated DOAC levels, whereas global coagulation tests are not recommended to exclude clinically relevant DOAC levels. In urgent clinical situations, haemostatic treatment using either the direct reversal or nonspecific haemostatic agents should be started without waiting for DOAC level monitoring. DOAC levels above 50 ng ml-1 may be considered clinically relevant necessitating haemostatic treatment before urgent or emergency procedures. Before cardiac surgery under activated factor Xa (FXa) inhibitors, the use of andexanet alfa is not recommended because of inhibition of unfractionated heparin, which is needed for extracorporeal circulation. In the situation of DOAC overdose without bleeding, no haemostatic intervention is suggested, instead measures to eliminate the DOACs should be taken. Due to the lack of published results from comparative prospective, randomised studies, the superiority of reversal treatment strategy vs. a nonspecific haemostatic treatment is unclear for most urgent and emergency procedures and bleeding. Due to the paucity of clinical data, no recommendations for the use of recombinant activated factor VII as a nonspecific haemostatic agent can be given., Conclusion: In the clinical scenarios of DOAC intake before urgent procedures and DOAC-induced bleeding, practitioners should evaluate the risk of bleeding of the procedure and the severity of the DOAC-induced bleeding before initiating treatment. Optimal reversal strategy remains to be determined in future trials for most clinical settings., (Copyright © 2024 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Purpose of Review: Tranexamic acid is routinely used as part of the management of traumatic bleeding. The dose recommendation in trauma was extrapolated from other clinical settings and the results of pragmatic randomized trials rather than pharmaco-kinetic and -dynamic evaluations. The review addresses current evidence on dosing of tranexamic acid in traumatized patients with a focus on efficacy, safety and risk-benefit profile., Recent Findings: A majority, but not all, of existing randomized clinical trials reports a reduction in mortality and/or blood loss with tranexamic acid administration. Increasing dose above the general recommendation (1 g bolus + 1 g infusion/8 h intravenously) has not been shown to further increase efficacy and could potentially increase side effects., Summary: The benefit of tranexamic acid as adjuvant therapy in the management of bleeding trauma patients on mortality and transfusion requirements is clear and well documented, being most effective if given early and to patients with clinical signs of hemorrhagic shock. Recent reports suggest that in some patients presenting with a shutdown of their fibrinolytic pathway the administration of tranexamic acid could be associated with an increased risk of thromboembolic events and poor outcomes. A more personalized approach based on bedside assessment of fibrinolytic activation and pharmacokinetic-based dose regimen should be developed moving forward., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: A main cause of trauma morbidity and mortality is multiple-organ failure, and endotheliopathy has been implicated. Pilot studies indicate that low-dose prostacyclin improves endothelial functionality in critically ill patients, suggesting that this intervention may improve trauma patient outcome., Methods: We conducted a multicenter, randomized, blinded, clinical investigator-initiated trial in 229 trauma patients with hemorrhagic shock who were randomized 1:1 to 72 hours infusion of the prostacyclin analog iloprost (1 ng/kg/min) or placebo. The primary outcome was the number of intensive care unit (ICU)-free days alive within 28 days of admission. Secondary outcomes included 28-day all-cause mortality and hospital length of stay., Results: The mean number of ICU-free days alive within 28 days was 15.64 days in the iloprost group versus 13.99 days in the placebo group (adjusted mean difference, -1.63 days [95% confidence interval (CI), -4.64 to 1.38 days]; p = 0.28). The 28-day mortality was 18.8% in the iloprost group versus 19.6% in the placebo group (odds ratio, 1.01 [95% CI, 0.51-2.0]; p = 0.97). The mean hospital length of stay was 19.96 days in the iloprost group versus 27.32 days in the placebo group (adjusted mean difference, 7.84 days [95% CI, 1.66-14.02 days], p = 0.01)., Conclusion: Iloprost did not result in a statistically significant increase in the number of ICU-free days alive within 28 days of admission, whereas it was safe and a statistically significant reduction in hospital length of stay was observed. Further research on prostacyclin in shocked trauma patients is warranted., Level of Evidence: Therapeutic/Care Management; Level II., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Surgery of Trauma.)

Thrombosis and bleeding are significant contributors to morbidity and mortality in patients with hematological cancer, and the impact of altered fibrinolysis on bleeding and thrombosis risk is poorly understood. In this prospective cohort study, we investigated the dynamics of fibrinolysis in patients with hematological cancer. Fibrinolysis was investigated before treatment and 3 months after treatment initiation. A dynamic clot formation and lysis assay was performed beyond the measurement of plasminogen activator inhibitor 1, tissue- and urokinase-type plasminogen activators (tPA and uPA), plasmin-antiplasmin complexes (PAP), α-2-antiplasmin activity, and plasminogen activity. Clot initiation, clot propagation, and clot strength were assessed using rotational thromboelastometry. A total of 79 patients were enrolled. Patients with lymphoma displayed impaired fibrinolysis with prolonged 50% clot lysis time compared with healthy controls (P = .048). They also displayed decreased clot strength at follow-up compared with at diagnosis (P = .001). A patient with amyloid light-chain amyloidosis having overt bleeding at diagnosis displayed hyperfibrinolysis, indicated by a reduced 50% clot lysis time, α-2-antiplasmin activity, and plasminogen activity, and elevated tPA and uPA. A patient with acute promyelocytic leukemia also displayed marked hyperfibrinolysis with very high PAP, indicating extreme plasmin generation, and clot formation was not measurable, probably because of the extremely fast fibrinolysis. Fibrinolysis returned to normal after treatment in both patients. In conclusion, patients with lymphoma showed signs of impaired fibrinolysis and increased clot strength, whereas hyperfibrinolysis was seen in patients with acute promyelocytic leukemia and light-chain amyloidosis. Thus, investigating fibrinolysis in patients with hematological cancer could have diagnostic value., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Introduction: Supplemental oxygen is commonly used in trauma patients, although it may lead to hyperoxaemia that has been associated with pulmonary complications and increased mortality. The primary objective of this trial, TRAUMOX2, is to compare a restrictive versus liberal oxygen strategy the first 8 hours following trauma., Methods and Analysis: TRAUMOX2 is an investigator-initiated, international, parallel-grouped, superiority, outcome assessor-blinded and analyst-blinded, randomised, controlled, clinical trial.Adult patients with suspected major trauma are randomised to eight hours of a restrictive or liberal oxygen strategy. The restrictive group receives the lowest dosage of oxygen ( > 21%) that ensures an SpO 2 of 94%. The liberal group receives 12-15 L O 2 /min or FiO 2 =0.6-1.0.The primary outcome is a composite of 30-day mortality and/or development of major respiratory complications (pneumonia and/or acute respiratory distress syndrome).With 710 participants in each arm, we will be able to detect a 33% risk reduction with a restrictive oxygen strategy if the incidence of our primary outcome is 15% in the liberal group., Ethics and Dissemination: TRAUMOX2 is carried out in accordance with the Helsinki II Declaration. It has been approved by the Danish Committee on Health Research Ethics for the Capital Region (H-21018062) and The Danish Medicines Agency, as well as the Dutch Medical Research Ethics Committee Erasmus MS (NL79921.078.21 and MEC-2021-0932). A website (www.traumox2.org) is available for updates and study results will be published in an international peer-reviewed scientific journal., Trial Registration Numbers: EudraCT 2021-000556-19; NCT05146700., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The main goal of perioperative coagulation monitoring is to improve safety of patients undergoing surgical procedures. Various conditions can affect the coagulation system during surgery and bleeding. The value of traditional standard coagulation tests is limited in detecting hemostatic dysfunctions and they are particularly ineffective in diagnosing hyperfibrinolysis. This article reports on key issues and pathophysiologic changes that affect the hemostatic system in the perioperative setting. Values of preoperative coagulation tests are discussed and the basic principles for point-of-care coagulation devices, including platelet analyzers and their clinical use, are evaluated., Competing Interests: Disclosure Author received unrestricted grants/travel support from Instrumentation Laboratory, Tem Innovations, CSL Behring, and Portola., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Antifibrinolytic drugs are used to reduce blood loss and subsequent transfusions during surgery and following trauma, but the optimal dosing regimen in the pediatric population is still unresolved. The aim of this systematic review was to evaluate efficacy and safety of antifibrinolytic drugs in pediatric surgery and trauma to determine the optimal dosing regimen. A literature search was performed in PubMed, Embase, Cochrane, and Web of Science on May 3, 2020. We included randomized controlled studies investigating the effect of tranexamic acid (TXA), aprotinin, and epsilon-aminocaproic acid, in terms of reducing blood loss, blood transfusions, reoperations, and rebleeds in pediatric patients aged 0 to 18 years undergoing cardiac surgery, noncardiac surgery, or trauma. Fifty randomized controlled trials (RCTs) were included; 28 RCTs investigated cardiac surgery and 22 investigated noncardiac surgery. No RCTs regarding trauma met the inclusion criteria. All antifibrinolytic drugs reduced postoperative blood loss and transfusions when used in pediatric surgery. The dosing regimen varied between studies, but similar effect sizes were found in terms of reduced blood loss regardless of the cumulative dose used. Few studies found adverse events, and no difference in incidence or type of adverse events was seen between the antifibrinolytic and the placebo group. In conclusion, use of antifibrinolytics is efficient and safe in children undergoing surgery. We propose TXA as the drug of choice based on its level of evidence and safety profile; we recommend a dosing regimen composed of a loading dose of 10 to 15 mg/kg prior to surgery followed by 1 to 5 mg/kg/h as continuous infusion throughout surgery., Competing Interests: None declared., (Thieme. All rights reserved.)

Introduction: Prehospital blood component therapy poses a possible treatment option among patients with severe bleeding. The aim of this paper was to characterize patients receiving prehospital blood component therapy by a paramedic-doctor-staffed, ground-based prehospital critical care (PHCC) service., Methods: Bleeding patients with a clinical need for prehospital blood transfusion were included prospectively. The following data were collected: indication for transfusion, mechanism of injury, vital parameters, units of red blood cells (RBCs)/plasma transfused, degree of shock, demographics, and mortality., Results: Twenty-one patients received blood products: 12 (57%) traumatic injuries and nine (43%) non-traumatic bleeds, with a median of 1.5 (range 1.0-2.0) units of RBCs and 1.0 (range 0.0-2.0) unit of plasma. The most frequent trigger to initiate transfusion was on-going excessive bleeding and hypotension. Improved systolic blood pressure (SBP) and milder degrees of shock were observed after transfusion. Mean time from initiation of transfusion to hospital arrival was 24 minutes. In-hospital, 11 patients (61%) received further transfusion and 13 (72%) had urgent surgery within 24 hours. Overall, 28-day mortality was 29% at 24-hours and 33% at 28-days., Conclusion: Prehospital blood component therapy is feasible in a ground-based prehospital service in a medium-sized Scandinavian city. Following transfusion, patient physiology and degree of shock were significantly improved.

Background: Tranexamic acid (TXA) reduces blood loss and transfusion requirements during craniosynostosis surgery in small children. Possible interaction from TXA on the inflammatory system is unknown., Objective: To evaluate the effect of TXA on a wide range of inflammatory markers in children receiving TXA in a randomized, blinded, and placebo controlled study design., Methods: Thirty children undergoing craniosynostosis surgery with significant blood loss received TXA (bolus dose of 10 mg kg -1 followed by 8 hours continuous infusion of 3 mg kg -1  h -1 ) or placebo in a randomized, double-blinded study design. Using a new proximity extension assays employing a panel of inflammatory biomarkers samples was used for analysis of blood samples obtained pre-operatively, 4 and 24 hours after operation., Results: Ninety-two inflammatory parameters were measured. TXA did not affect any of the measured parameters as compared with placebo. Among 34 of the 92 pro- and antiinflammatory parameters investigated changes were observed between pre-operative, 4 or 24 hours, respectively, reflecting immune activation during surgical stress., Conclusion: TXA administration in a low-dose regimen including bolus followed by 8 hours infusion during craniosynostosis surgery did not change any of 92 inflammatory markers as compared with placebo., (© 2020 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Objective:  Craniosynostosis surgery in small children is very often associated with a high blood loss. Tranexamic acid (TXA) reduces blood loss during this procedure, although the potential underlying coagulopathy in these children is not known in detail. Objective was to determine the nature of any coagulopathy found during and after craniosynostosis surgery and to characterize the effect of TXA on fibrin clot formation, clot strength, and fibrinolysis., Materials and Methods:  Thirty children received either TXA (bolus dose of 10 mg/kg followed by 8 hours continuous infusion of 3 mg/kg/h) or placebo. Dynamic whole blood clot formation assessed by thromboelastometry, platelet count, dynamic thrombin generation/thrombin-antithrombin, clot lysis assay, and fibrinogen/factor XIII (FXIII) levels were measured. Additionally, clot structure was investigated by real-time live confocal microscopy and topical data analysis., Results:  Increased ability of thrombin generation was observed together with a tendency toward shortened activated partial thromboplastin time and clotting time. Postoperative maximum clot firmness was higher among children receiving TXA. FXIII decreased significantly during surgery in both groups.Resistance toward tissue plasminogen activator-induced fibrinolysis was higher in children that received TXA, as evidenced by topical data analysis and by a significant longer lysis time. Fibrinogen levels were higher in the TXA group at 24 hours., Conclusion:  A significant coagulopathy mainly characterized by changes in clot stability and not parameters of thrombin generation was reported. Tranexamic acid improved clot strength and reduced fibrinolysis, thereby avoiding reduction in fibrinogen levels., Competing Interests: The authors declare no conflicts of interest with regard to the present manuscript. Dr. Hvas reports other from CSL Behring, other from Astellas, and other from Bayer A/S, outside the submitted work. Dr. Rasmussen reports grants from Health Research Foundation of Central Denmark Region, during the conduct of the study., (Georg Thieme Verlag KG Stuttgart · New York.)

Pediatric craniosynostosis (CS) surgery is frequently associated with extensive blood loss and transfusion requirements. The aim of the study was to evaluate the authors' institutional procedure with 2-surgeon approach and early transfusion strategy on blood loss and blood product transfusions in children undergoing craniofacial surgery. A retrospective analysis of medical records was performed of pediatric CS corrections during a 15-year period. Primary endpoint was blood loss and transfusion requirement during and the following 24 hours postoperatively. Linear regression analyses were performed of associations between intra and- postoperative blood loss and blood loss and weight. A total of 276 children (median 9 months) were included. Intraoperative blood loss was 22 mL/kg (14-33 mL/kg) and postoperatively 27 mL/kg (18-37 mL/kg), with no change during the study period. Intraoperative transfusions of red blood cell and plasma were 16 mL/kg (10-24 mL/kg) and postoperative 14 mL/kg (9-21 mL/kg). Postoperative red blood cell and plasma transfusions were 2 mL/kg (0-6 mL/kg) and of 0 mL/kg, respectively. Craniosynostosis type was related to blood loss (P < 0.001). There was an association between intraoperative and postoperative blood loss (P = 0.012) and intra- and postoperative blood loss and weight (P = 0.002, P = < 0.001). Duration of surgery was 110 minutes (range 60-300 minutes).Pediatric CS surgery is associated with substantial intra- and postoperative blood loss and transfusion requirements, which did not change over a 15-year period. Blood loss was associated with type of CS. Intraoperative blood loss was correlated to postoperative blood loss and body weight.

Background: Tranexamic acid (TXA) reduces intraoperative blood loss and transfusion during paediatric craniosynostosis surgery. Additional reduction of postoperative blood loss may further reduce exposure to allogeneic blood products. We studied the effect of combined intra- and postoperative TXA treatment on postoperative blood loss in children., Methods: Thirty children admitted for craniosynostosis surgery were randomised to combined intra- and postoperative TXA treatment or placebo. The primary endpoint was postoperative blood loss. Secondary endpoints included total blood loss, transfusion requirements, and clot stability evaluated by tissue plasminogen activator-stimulated clot lysis assay., Results: TXA reduced postoperative blood loss by 18 ml kg -1 (95% confidence interval 8.9) and total blood loss from a mean of 52 ml kg -1 (standard deviation [SD]; 20) ml kg -1 to 28 (14) ml kg -1 (P<0.001). Intraoperative red blood cell (RBC) and fresh frozen plasma (FFP) transfusions were reduced in the treatment group from RBC 14.0 (5.2) ml kg -1 to 8.2 (5.1) ml kg -1 (P=0.01) and from FFP 13.0 (6.3) ml kg -1 to 7.8 (5.9) ml kg -1 (P=0.03). Postoperative RBC transfusion median was 5 (inter-quartile range [IQR] 0-6) ml kg -1 in the placebo group and 0 (0-5.7) ml kg -1 in the TXA group. Resistance to lysis was higher in the treatment group (P<0.001)., Conclusions: Combined intra- and postoperative tranexamic acid treatment reduced postoperative and overall blood loss and transfusion requirements. Improved clot stability represents a possible mechanism for blood loss reduction., (Copyright © 2019 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: Central neuraxial blocks (CNB: epidural, spinal and their combinations) and other spinal pain procedures can cause serious harm to the spinal cord in patients on antihaemostatic drugs or who have other risk-factors for bleeding in the spinal canal. The purpose of this narrative review is to provide a practise advisory on how to reduce risk of spinal cord injury from spinal haematoma (SH) during CNBs and other spinal pain procedures. Scandinavian guidelines from 2010 are part of the background for this practise advisory., Methods: We searched recent guidelines, PubMed (MEDLINE), SCOPUS and EMBASE for new and relevant randomised controlled trials (RCT), case-reports and original articles concerning benefits of neuraxial blocks, risks of SH due to anti-haemostatic drugs, patient-related risk factors, especially renal impairment with delayed excretion of antihaemostatic drugs, and specific risk factors related to the neuraxial pain procedures., Results and Recommendations: Epidural and spinal analgesic techniques, as well as their combination provide superior analgesia and reduce the risk of postoperative and obstetric morbidity and mortality. Spinal pain procedure can be highly effective for cancer patients, less so for chronic non-cancer patients. We did not identify any RCT with SH as outcome. We evaluated risks and recommend precautions for SH when patients are treated with antiplatelet, anticoagulant, or fibrinolytic drugs, when patients' comorbidities may increase risks, and when procedure-specific risk factors are present. Inserting and withdrawing epidural catheters appear to have similar risks for initiating a SH. Invasive neuraxial pain procedures, e.g. spinal cord stimulation, have higher risks of bleeding than traditional neuraxial blocks. We recommend robust monitoring routines and treatment protocol to ensure early diagnosis and effective treatment of SH should this rare but potentially serious complication occur., Conclusions: When neuraxial analgesia is considered for a patient on anti-haemostatic medication, with patient-related, or procedure-related risk factors, the balance of benefits against risks of bleeding is decisive; when CNB are offered exclusively to patients who will have a reduction of postoperative morbidity and mortality, then a higher risk of bleeding may be accepted. Robust routines should ensure appropriate discontinuation of anti-haemostatic drugs and early detection and treatment of SH., Implications: There is an on-going development of drugs for prevention of thromboembolic events following surgery and childbirth. The present practise advisory provides up-to-date knowledge and experts' experiences so that patients who will greatly benefit from neuraxial pain procedures and have increased risk of bleeding can safely benefit from these procedures. There are always individual factors for the clinician to evaluate and consider. Increasingly it is necessary for the anaesthesia and analgesia provider to collaborate with specialists in haemostasis. Surgeons and obstetricians must be equally well prepared to collaborate for the best outcome for their patients suffering from acute or chronic pain. Optimal pain management is a prerequisite for enhanced recovery after surgery, but there is a multitude of additional concerns, such as early mobilisation, early oral feeding and ileus prevention that surgeons and anaesthesia providers need to optimise for the best outcome and least risk of complications.

: Institutional protocols need to address the indications for pharmacological and mechanical thromboprophylaxis. The use of graduated compression stockings (GCS) and intermittent pneumatic compression (IPC) strongly differs between institutions. As a consequence, no strong recommendations can be made based on the contemporary high-level evidence. Although different clinical practices can be supported, such approaches should be part of an institutional strategy to reduce the burden of venous thromboembolism (VTE). We recommend against the use of GCS alone without pharmacological thromboprophylaxis for prevention of VTE in patients at intermediate and high risk. For patients at high risk of VTE with contraindications for pharmacological thromboprophylaxis, we recommend the use of mechanical prophylaxis and suggest the use of IPC over GCS. However, for those patients receiving pharmacological thromboprophylaxis who are without a very high risk of VTE prophylaxis, we recommend against the routine use of mechanical thromboprophylaxis either with GCS or IPC. We suggest combined mechanical and pharmacological prophylaxis in selected patients at very high risk of VTE prophylaxis and suggest IPC rather than GCS in these selected patients.

: The risk for postoperative venous thromboembolism (VTE) is increased in patients aged more than 70 years and in elderly patients presenting with co-morbidities, for example cardiovascular disorders, malignancy or renal insufficiency. Therefore, risk stratification, correction of modifiable risks and sustained perioperative thromboprophylaxis are essential in this patient population. Timing and dosing of pharmacoprophylaxis may be adopted from the non-aged population. Direct oral anti-coagulants are effective and well tolerated in the elderly; statins may not replace pharmacological thromboprophylaxis. Early mobilisation and use of non-pharmacological means of thromboprophylaxis should be exploited. In elderly patients, we suggest identification of co-morbidities increasing the risk for VTE (e.g. congestive heart failure, pulmonary circulation disorder, renal failure, lymphoma, metastatic cancer, obesity, arthritis, post-menopausal oestrogen therapy) and correction if present (e.g. anaemia, coagulopathy) (Grade 2C). We suggest against bilateral knee replacement in elderly and frail patients (Grade 2C). We suggest timing and dosing of pharmacological VTE prophylaxis as in the non-aged population (Grade 2C). In elderly patients with renal failure, low-dose unfractionated heparin (UFH) may be used or weight-adjusted dosing of low molecular weight heparin (Grade 2C). In the elderly, we recommend careful prescription of postoperative VTE prophylaxis and early postoperative mobilisation (Grade 1C). We recommend multi-faceted interventions for VTE prophylaxis in elderly and frail patients, including pneumatic compression devices, low molecular weight heparin (and/or direct oral anti-coagulants after knee or hip replacement) (Grade 1C). : This article is part of the European guidelines on perioperative venous thromboembolism prophylaxis. For details concerning background, methods, and members of the ESA VTE Guidelines Task Force, please, refer to:Samama CM, Afshari A, for the ESA VTE Guidelines Task Force. European guidelines on perioperative venous thromboembolism prophylaxis. Eur J Anaesthesiol 2018; 35:73-76.A synopsis of all recommendations can be found in the following accompanying article: Afshari A, Ageno W, Ahmed A, et al., for the ESA VTE Guidelines Task Force. European Guidelines on perioperative venous thromboembolism prophylaxis. Executive summary. Eur J Anaesthesiol 2018; 35:77-83.

Background: Cardiac surgery may cause a serious coagulopathy leading to increased risk of bleeding and transfusion demands. Blood bank products are commonly first line haemostatic intervention, but has been associated with hazardous side effect. Coagulation factor concentrates may be a more efficient, predictable, and potentially a safer treatment, although prospective clinical trials are needed to further explore these hypotheses. This study investigated the haemostatic potential of ex vivo supplementation of coagulation factor concentrates versus blood bank products on blood samples drawn from patients undergoing cardiac surgery., Methods: 30 adults were prospectively enrolled (mean age=63.9, females=27%). Ex vivo haemostatic interventions (monotherapy or combinations) were performed in whole blood taken immediately after surgery and two hours postoperatively. Fresh-frozen plasma, platelets, cryoprecipitate, fibrinogen concentrate, prothrombin complex concentrate (PCC), and recombinant FVIIa (rFVIIa) were investigated. The haemostatic effect was evaluated using whole blood thromboelastometry parameters, as well as by thrombin generation., Results: Immediately after surgery the compromised maximum clot firmness was corrected by monotherapy with fibrinogen or platelets or combination therapy with fibrinogen. At two hours postoperatively the coagulation profile was further deranged as illustrated by a prolonged clotting time, a reduced maximum velocity and further diminished maximum clot firmness. The thrombin lagtime was progressively prolonged and both peak thrombin and endogenous thrombin potential were compromised. No monotherapy effectively corrected all haemostatic abnormalities. The most effective combinations were: fibrinogen+rFVIIa or fibrinogen+PCC. Blood bank products were not as effective in the correction of the coagulopathy., Conclusion: Coagulation factor concentrates appear to provide a more optimal haemostasis profile following cardiac surgery compared to blood bank products., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Tranexamic acid inhibits the degradation of a newly formed fibrin clot. The drug reduces blood loss and transfusion requirements in a wide range of different clinical scenarios and patient settings. So far, tranexamic acid is not part of standard treatment among patients with gastrointestinal bleeding. This article evaluates the available literature on this topic. Tranexamic acid seems appropriate as adjuvant treatment during upper gastrointestinal bleeding. However, these patients are often old and have several co-morbidities. Therefore, thromboembolic risk and tranexamic acid dosage should be carefully evaluated.

Background: Total thrombus formation velocity calculated using amplitude parameters obtained at different times could be used to estimate the amplification and the propagation phases observed during coagulation processes, and therefore might be useful to predict postoperative hemostatic products administration in pediatric patients., Methods: We retrospectively analyzed data from 49 children <3 months of age who underwent cardiac surgery. Children ≤1 month of age routinely received fresh frozen plasma during bypass while children >1 month of age did not. The EXTEM parameters were used to calculate velocity curves using amplitudes obtained at different times, the area under the curve called total thrombus formation and the maximum rate of thrombus formation. These parameters were compared between children who received fresh frozen plasma and those who did not. Receiver operating characteristics curves were used to define variables that could be used to predict postoperative fresh frozen plasma transfusion., Results: Total thrombus formation and maximum rate of thrombus formation significantly increased in children who received fresh frozen plasma compared to those who did not. Both total thrombus formation and maximum rate of thrombus formation have a better specificity to predict postoperative fresh frozen plasma transfusion compared to clotting time or maximal clot firmness., Conclusion: Based on this descriptive study, dynamic ROTEM(®) parameters of total thrombus formation could be used to estimate the amplification and the propagation phases of coagulation in children. These parameters might be used in further well-designed study to predict the need for hemostatic products in children undergoing cardiac surgery with cardiopulmonary bypass., (© 2015 John Wiley & Sons Ltd.)

We describe two cases of acute liver failure following heat stroke after participation in a running event. At admission both patients had a severely affected circulation, altered consciousness and hyperthermia, with a core temperature of > 40 degrees Celsius. Within the first 24 hours both patients suffered from acute liver failure, kidney failure and coagulopathy. No other causes but dehydration and hyperthermia could explain the liver failure. The treatment of heat stroke is symptomatic, but liver transplantation may be an option in case of fulminant liver failure.