Management of severe peri-operative bleeding: Guidelines from the European Society of Anaesthesiology and Intensive Care: Second update 2022.

BACKGROUND: Management of peri-operative bleeding is complex and involves multiple assessment tools and strategies to ensure optimal patient care with the goal of reducing morbidity and mortality. These updated guidelines from the European Society of Anaesthesiology and Intensive Care (ESAIC) aim to provide an evidence-based set of recommendations for healthcare professionals to help ensure improved clinical management. DESIGN: A systematic literature search from 2015 to 2021 of several electronic databases was performed without language restrictions. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was used to assess the methodological quality of the included studies and to formulate recommendations. A Delphi methodology was used to prepare a clinical practice guideline. RESULTS: These searches identified 137 999 articles. All articles were assessed, and the existing 2017 guidelines were revised to incorporate new evidence. Sixteen recommendations derived from the systematic literature search, and four clinical guidances retained from previous ESAIC guidelines were formulated. Using the Delphi process on 253 sentences of guidance, strong consensus (>90% agreement) was achieved in 97% and consensus (75 to 90% agreement) in 3%. DISCUSSION: Peri-operative bleeding management encompasses the patient's journey from the pre-operative state through the postoperative period. Along this journey, many features of the patient's pre-operative coagulation status, underlying comorbidities, general health and the procedures that they are undergoing need to be taken into account. Due to the many important aspects in peri-operative nontrauma bleeding management, guidance as to how best approach and treat each individual patient are key. Understanding which therapeutic approaches are most valuable at each timepoint can only enhance patient care, ensuring the best outcomes by reducing blood loss and, therefore, overall morbidity and mortality. CONCLUSION: All healthcare professionals involved in the management of patients at risk for surgical bleeding should be aware of the current therapeutic options and approaches that are available to them. These guidelines aim to provide specific guidance for bleeding management in a variety of clinical situations.

Collaboration for Evidence-based Practice and Research in Anaesthesia (CEPRA): A consortium initiative for perioperative research.

Evidence in perioperative care is insufficient. There is an urgent need for large perioperative research programmes, including pragmatic randomised trials, testing daily clinical treatments and unanswered question, thereby providing solid evidence for effects of interventions given to a large and growing number of patients undergoing surgery and anaesthesia. This may be achieved through large collaborations. Collaboration for Evidence-based Practice and Research in Anaesthesia (CEPRA) is a novel collaborative research network founded to pursue evidence-based answers to major clinical questions in perioperative medicine. The aims of CEPRA are to (1) improve clinical treatment and outcomes and optimise the use of resources for patients undergoing anaesthesia and perioperative care, and (2) disseminate results and inform caretakers, patients and relatives, and policymakers of evidence-based treatments in anaesthesia and perioperative medicine. CEPRA is inclusive in its concept. We aim to extend our collaboration with all relevant clinical collaborators and patient associations and representatives. Although initiated in Denmark, CEPRA seeks to develop an international network infrastructure, for example, with other Nordic countries. The work of CEPRA will follow the highest methodological standards. The organisation aims to structure and optimise any element of the research collaboration to reduce economic costs and harness benefits from well-functioning research infrastructure. This includes successive continuation of trials, harmonisation of outcomes, and alignment of data management systems. This paper presents the initiation and visions of the CEPRA network. CEPRA aims to be inclusive, patient-focused, methodologically sound, and to optimise all aspects of research logistics. This will translate into faster research conduct, reliable results, and accelerated clinical implementation of results, thereby benefiting millions of patients whilst being cost and labour-saving.

Recombinant factor VIIa in postpartum haemorrhage.

Recombinant factor VIIa (rFVIIa) has of April 2022 been approved by the European Medicines Agency for treatment of severe postpartum haemorrhage. The extended approval is based on one small open-label, non-blinded randomized trial of 84 women from 2015 showing reduced "second line" treatment, but also increased risk of thromboembolism. Systematic use of tranexamic acid and timely coagulation assessment with thromboelastography/rotational thromboelastometry are not applied. Danish and international societies recommend that rFVIIa is reserved as a last option in severe life-threatening cases of postpartum haemorrhage.

General or regional anaesthesia for postpartum haemorrhage-A national population-based cohort study.

BACKGROUND: Anaesthesia is required to assist the treatment of postpartum haemorrhage (PPH) when manual removal of the placenta or emptying of the uterine cavity is required. The choice between general or regional anaesthesia may depend upon factors such as existing epidural, airway, hypovolaemia, and tradition. METHODS: Data from a randomized controlled trial of PPH (FIB-PPH) was used to reveal differences between delivery centres. In addition, national data of 5,601 PPH procedures requiring anaesthesia during 2010-2015 was collected from the Danish Medical Birth Registry, the National Danish Patient Registry, and the Danish Anaesthesia Database. The aim is to describe the variation in choice of anaesthesia for treatment of PPH. RESULTS: Data from the randomized trial showed large differences in practice between centres not explained by physiological factors. Using national Danish registry data, we show that large delivery centres as compared to small centres prefer regional anaesthesia for PPH procedures in opposed to general anaesthesia. Sevoflurane was used despite it causing uterine relaxation. The use of general anaesthesia was associated with younger parturients, larger blood loss, and larger Body-Mass Index. Aspiration was recorded in one case (0.02%). In the postoperative care-unit general anaesthesia was associated with a shorter stay, but also higher pain score at admission. CONCLUSION: Practice varies immensely between delivery centres with large centres preferring regional anaesthesia. Difference in practice might be explained by level of experience, here large centres might be more confident using regional anaesthesia. Knowledge is being extrapolated from literature on caesarean sections. Future studies should address the optimal choice of anaesthesia for PPH procedures.

The increasing role of a retained placenta in postpartum blood loss: a cohort study.

PURPOSE: To describe the association between quantity of blood loss, duration of the third stage of labour, retained placenta and other risk factors, and to describe the role of a retained placenta depending on the cutoff used to define postpartum haemorrhage. METHODS: Cohort study of all vaginal deliveries at two Danish maternity units between 1 January 2009 and 31 December 2013 (n = 43,357), univariate and multivariate linear regression statistical analyses. RESULTS: A retained placenta was shown to be a strong predictor of quantity of blood loss and duration of the third stage of labour a weak predictor of quantity of blood loss. The predictive power of the third stage of labour was further reduced in the multivariate analysis when including retained placenta in the model. There was an increase in the role of a retained placenta depending on the cutoff used to define postpartum haemorrhage, increasing from 12% in cases of blood loss ≥ 500 ml to 53% in cases of blood loss ≥ 2000 ml CONCLUSION: The predictive power of duration of the third stage of labour in regard to postpartum blood loss was diminished by the influence of a retained placenta. A retained placenta was, furthermore, present in the majority of most severe cases.

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

: The management of perioperative bleeding involves multiple assessments and strategies to ensure appropriate patient care. Initially, it is important to identify those patients with an increased risk of perioperative bleeding. Next, strategies should be employed to correct preoperative anaemia and to stabilise macrocirculation and microcirculation to optimise the patient's tolerance to bleeding. Finally, targeted interventions should be used to reduce intraoperative and postoperative bleeding, and so prevent subsequent morbidity and mortality. The objective of these updated guidelines is to provide healthcare professionals with an overview of the most recent evidence to help ensure improved clinical management of patients. For this update, electronic databases were searched without language restrictions from 2011 or 2012 (depending on the search) until 2015. These searches produced 18 334 articles. All articles were assessed and the existing 2013 guidelines were revised to take account of new evidence. This update includes revisions to existing recommendations with respect to the wording, or changes in the grade of recommendation, and also the addition of new recommendations. The final draft guideline was posted on the European Society of Anaesthesiology website for four weeks for review. All comments were collated and the guidelines were amended as appropriate. This publication reflects the output of this work.

Thromboelastography (TEG) or thromboelastometry (ROTEM) to monitor haemostatic treatment versus usual care in adults or children with bleeding.

BACKGROUND: Severe bleeding and coagulopathy are serious clinical conditions that are associated with high mortality. Thromboelastography (TEG) and thromboelastometry (ROTEM) are increasingly used to guide transfusion strategy but their roles remain disputed. This review was first published in 2011 and updated in January 2016. OBJECTIVES: We assessed the benefits and harms of thromboelastography (TEG)-guided or thromboelastometry (ROTEM)-guided transfusion in adults and children with bleeding. We looked at various outcomes, such as overall mortality and bleeding events, conducted subgroup and sensitivity analyses, examined the role of bias, and applied trial sequential analyses (TSAs) to examine the amount of evidence gathered so far. SEARCH METHODS: In this updated review we identified randomized controlled trials (RCTs) from the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 1); MEDLINE; Embase; Science Citation Index Expanded; International Web of Science; CINAHL; LILACS; and the Chinese Biomedical Literature Database (up to 5 January 2016). We contacted trial authors, authors of previous reviews, and manufacturers in the field. The original search was run in October 2010. SELECTION CRITERIA: We included all RCTs, irrespective of blinding or language, that compared transfusion guided by TEG or ROTEM to transfusion guided by clinical judgement, guided by standard laboratory tests, or a combination. We also included interventional algorithms including both TEG or ROTEM in combination with standard laboratory tests or other devices. The primary analysis included trials on TEG or ROTEM versus any comparator. DATA COLLECTION AND ANALYSIS: Two review authors independently abstracted data; we resolved any disagreements by discussion. We presented pooled estimates of the intervention effects on dichotomous outcomes as risk ratio (RR) with 95% confidence intervals (CIs). Due to skewed data, meta-analysis was not provided for continuous outcome data. Our primary outcome measure was all-cause mortality. We performed subgroup and sensitivity analyses to assess the effect based on the presence of coagulopathy of a TEG- or ROTEM-guided algorithm, and in adults and children on various clinical and physiological outcomes. We assessed the risk of bias through assessment of trial methodological components and the risk of random error through TSA. MAIN RESULTS: We included eight new studies (617 participants) in this updated review. In total we included 17 studies (1493 participants). A total of 15 trials provided data for the meta-analyses. We judged only two trials as low risk of bias. The majority of studies included participants undergoing cardiac surgery.We found six ongoing trials but were unable to retrieve any data from them. Compared with transfusion guided by any method, TEG or ROTEM seemed to reduce overall mortality (7.4% versus 3.9%; risk ratio (RR) 0.52, 95% CI 0.28 to 0.95; I(2) = 0%, 8 studies, 717 participants, low quality of evidence) but only eight trials provided data on mortality, and two were zero event trials. Our analyses demonstrated a statistically significant effect of TEG or ROTEM compared to any comparison on the proportion of participants transfused with pooled red blood cells (PRBCs) (RR 0.86, 95% CI 0.79 to 0.94; I(2) = 0%, 10 studies, 832 participants, low quality of evidence), fresh frozen plasma (FFP) (RR 0.57, 95% CI 0.33 to 0.96; I(2) = 86%, 8 studies, 761 participants, low quality of evidence), platelets (RR 0.73, 95% CI 0.60 to 0.88; I(2) = 0%, 10 studies, 832 participants, low quality of evidence), and overall haemostatic transfusion with FFP or platelets (low quality of evidence). Meta-analyses also showed fewer participants with dialysis-dependent renal failure.We found no difference in the proportion needing surgical reinterventions (RR 0.75, 95% CI 0.50 to 1.10; I(2) = 0%, 9 studies, 887 participants, low quality of evidence) and excessive bleeding events or massive transfusion (RR 0.38, 95% CI 0.38 to 1.77; I(2) = 34%, 2 studies, 280 participants, low quality of evidence). The planned subgroup analyses failed to show any significant differences.We graded the quality of evidence as low based on the high risk of bias in the studies, large heterogeneity, low number of events, imprecision, and indirectness. TSA indicates that only 54% of required information size has been reached so far in regards to mortality, while there may be evidence of benefit for transfusion outcomes. Overall, evaluated outcomes were consistent with a benefit in favour of a TEG- or ROTEM-guided transfusion in bleeding patients. AUTHORS' CONCLUSIONS: There is growing evidence that application of TEG- or ROTEM-guided transfusion strategies may reduce the need for blood products, and improve morbidity in patients with bleeding. However, these results are primarily based on trials of elective cardiac surgery involving cardiopulmonary bypass, and the level of evidence remains low. Further evaluation of TEG- or ROTEM-guided transfusion in acute settings and other patient categories in low risk of bias studies is needed.

Prothrombin complex concentrate for reversal of vitamin K antagonist treatment in bleeding and non-bleeding patients.

BACKGROUND: Treatment with vitamin K antagonists is associated with increased morbidity and mortality. Reversal therapy with prothrombin complex concentrate (PCC) is used increasingly and is recommended in the treatment of patients with bleeding complications undertaking surgical interventions, as well as patients at high risk of bleeding. Evidence is lacking regarding indication, dosing, efficacy and safety. OBJECTIVES: We assessed the benefits and harms of PCC compared with fresh frozen plasma in the acute medical and surgical setting involving vitamin K antagonist-treated bleeding and non-bleeding patients. We investigated various outcomes and predefined subgroups and performed sensitivity analysis. We examined risks of bias and applied trial sequential analyses (TSA) to examine the level of evidence, and we prepared a 'Risk of bias' table to test the quality of the evidence. SEARCH METHODS: We searched the following databases from inception to 1 May 2013: Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE (Ovid SP); EMBASE (Ovid SP); International Web of Science; Latin American and Caribbean Health Sciences Literature (LILACS) (via BIREME); the Chinese Biomedical Literature Database; advanced Google and the Cumulative Index to Nursing and Allied Health Literature (CINAHL). We applied a systematic and sensitive search strategy to identify relevant randomized clinical trials and imposed no language or date restrictions. We adapted our MEDLINE search strategy for searches in all other databases. We reran the search in October 2014 and found one potential new study of interest. We added this study to a list of 'Studies awaiting classification', and we will incorporate this study into the formal review findings at the time of the review update. SELECTION CRITERIA: We included randomized controlled trials (RCTs), irrespective of publication status, date of publication, blinding status, outcomes published or language. We contacted investigators and study authors to request relevant data. DATA COLLECTION AND ANALYSIS: Three review authors independently abstracted data and resolved disagreements by discussion. Our primary outcome measures were 'overall mortality longest follow-up' and 'overall 28-day mortality'. We performed subgroup analyses to assess the effects of PCC in adults in terms of various clinical and physiological outcomes. We presented pooled estimates of the effects of interventions on dichotomous outcomes as risk ratios (RRs), and on continuous outcomes as mean differences (MDs), with 95% confidence intervals (CIs). We assessed risk of bias by assessing trial methodological components and risk of random error through TSA. MAIN RESULTS: We included four RCTs with a total of 453 participants and determined that none of these trials had overall low risk of bias. We found six ongoing trials from which we were unable to retrieve further data. Three trials provided data on mortality. Meta-analysis showed no statistical effect on overall mortality (RR 0.93, 95% CI 0.37 to 2.33; very low quality of evidence). We were unable to associate use of PCC with the number of complications probably related to the intervention (RR 0.92, 95% CI 0.78 to 1.09; very low quality of evidence). Lack of transfusion data and apparent differences in study design prevented review authors from finding a beneficial effect of PCC in reducing the volume of fresh frozen plasma (FFP) transfused to reverse the effect of vitamin K antagonist treatment. The number of new occurrences of transfusion of red blood cells (RBCs) did not seem to be associated with the use of PCC (RR 1.08, 95% CI 0.82 to 1.43; very low quality of evidence). Still, the included studies demonstrate the possibility of equally reversing vitamin K-induced coagulopathy using PCC without the need for transfusion of FFP. No effect on other predefined outcomes was observed. AUTHORS' CONCLUSIONS: In the four included RCTs, use of prothrombin complex concentrate does not appear to reduce mortality or transfusion requirements but demonstrates the possibility of reversing vitamin K-induced coagulopathy without the need for transfusion of fresh frozen plasma. All included trials have high risk of bias and are underpowered to detect mortality, benefit or harm. Clinical and statistical heterogeneity is high, and definitions of clinically important outcomes such as adverse events are highly dissimilar between trials. Only weak observational evidence currently supports the use of PCC in vitamin K antagonist-treated bleeding and non-bleeding patients, and the current systematic review of RCTs does not support the routine use of PCC over FFP. Additional high-quality research is urgently needed.

The role of fibrinogen and haemostatic assessment in postpartum haemorrhage: preparations for a randomised controlled trial.

Pregnancy is a state of hypercoagulobility that might be an evolutionary way of protecting parturients from exsanguination following child birth. Observational studies suggest an association between a low level of fibrinogen (coagulation factor I) at the start of postpartum haemorrhage (PPH) and subsequent severity of bleeding. Fibrinogen concentrate may be prescribed to correct acquired hypofibrinogenaemia, but evidence is lacking regarding the treatment efficacy. This thesis assesses the current evidence for the use of fibrinogen concentrate and haemostatic assessment in bleeding patients with special attention to the obstetrical population. It includes five papers: In Paper I the benefits or harms of fibrinogen concentrate in bleeding patients in general was evaluated using a systematic Cochrane review methodology with metaanalysis of all published randomized controlled trials (RCTs). Six trials with high risk of bias were included (248 patients). Fibrinogen appeared to reduce the need of allogenic transfusions by 53%. However, the included trials were conducted only in an elective surgical setting with a population of mainly cardiac surgical patients. Paper II was also a systematic review based on Cochrane methodology evaluating the use of viscoelastic haemostatic assays to guide haemostatic transfusion in bleeding patients. Nine RCTs (776 patients) with high risk of bias were included primarily in elective cardiac surgical patients and none were specific for the obstetric subpopulation. Viscoelastic haemostatic assay guided transfusion algorithm reduced blood loss and the proportion of patients exposed to fresh frozen plasma (FFP) or platelets. In both studies, we were unable to make firm conclusion on our primary outcome, "all cause mortality" due to lack of adequate data. Paper III was based on two national Danish registries evaluating the predictability of postpartum blood transfusion. Prediction was found difficult. However, retained placental parts seemed to be the strongest predictor. Since this diagnosis is made very late and often in association with the onset of bleeding, tools to perform an early diagnosis is highly warranted. Paper IV includes recommendations of the European Society of Anaesthesiology regarding the use of fibrinogen concentrate in PPH, and is based on very weak (GRADE 2) evidence and low confidence in estimates of effect (GRADE C). Paper V describes the protocol for a RCT of early fibrinogen supplementation in women with severe postpartum haemorrhage. Several practical, ethical and trial management challenges need to be addressed when conducting independent clinical research involving parturients with severe bleeding, placebo-controlled and blinded administration of a drug in a multicenter set-up with enrolments during the entire day and with many personnel involved.

Prediction of postpartum blood transfusion--risk factors and recurrence.

OBJECTIVE: The aim was to find clinically useful risk factors for postpartum transfusion and to assess the joint predictive value in a population of women with a first and second delivery. METHODS: All Danish women with a first and second delivery from January 2001 to September 2009 who gave birth in a hospital that reported transfusion of red blood cells to a national database: A total of 96 545 women were included. RESULTS: Retained placental tissue explained more than all other risk factors in vaginal deliveries. Retained placental tissue at first delivery was associated with postpartum transfusion at a second vaginal delivery, and may also be used as an early predictor in parallel with a history of either placental abruption, postpartum transfusion or caesarean delivery. The positive predictive values of having more than one risk factor was low (2.2%-2.7%). CONCLUSIONS: Prediction of postpartum transfusion is difficult. Retained placental tissue is the strongest predictor of postpartum blood transfusion in vaginal deliveries. Retained placental tissue is usually diagnosed for the first time when the bleeding starts, which limits the clinical value of prediction. We need tools for an early diagnosis of retained placenta to intervene early before transfusion is needed.

Fibrinogen concentrate in bleeding patients.

BACKGROUND: Hypofibrinogenaemia is associated with increased morbidity and mortality, but the optimal treatment level, the use of preemptive treatment and the preferred source of fibrinogen remain disputed. Fibrinogen concentrate is increasingly used and recommended for bleeding with acquired haemostatic deficiencies in several countries, but evidence is lacking regarding indications, dosing, efficacy and safety. OBJECTIVES: We assessed the benefits and harms of fibrinogen concentrate compared with placebo or usual treatment for bleeding patients. SEARCH METHODS: We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 8); MEDLINE (1950 to 9 August 2013); EMBASE (1980 to 9 August 2013); International Web of Science (1964 to 9 August 2013); CINAHL (1980 to 9 August 2013); LILACS (1982 to 9 August 2013); and the Chinese Biomedical Literature Database (up to 10 November 2011), together with databases of ongoing trials. We contacted trial authors, authors of previous reviews and manufacturers in the field. SELECTION CRITERIA: We included all randomized controlled trials (RCTs), irrespective of blinding or language, that compared fibrinogen concentrate with placebo/other treatment or no treatment in bleeding patients, excluding neonates and patients with hereditary bleeding disorders. DATA COLLECTION AND ANALYSIS: Three review authors independently abstracted data; we resolved any disagreements by discussion. Our primary outcome measure was all-cause mortality. We performed subgroup and sensitivity analyses to assess the effects of fibrinogen concentrate in adults and children in terms of various clinical and physiological outcomes. We presented pooled estimates of the effects of intervention on dichotomous outcomes as risk ratios (RRs) and on continuous outcomes as mean differences, with 95% confidence intervals (CIs). We assessed the risk of bias through assessment of trial methodological components and the risk of random error through trial sequential analysis. MAIN RESULTS: We included six RCTs with a total of 248 participants; none of the trials were determined to have overall low risk of bias. We found 12 ongoing trials, from which we were unable to retrieve any data. Only two trials provided data on mortality, and one was a zero event study; thus the meta-analysis showed no statistically significant effect on overall mortality (2.6% vs 9.5%, RR 0.28, 95% CI 0.03 to 2.33). Our analyses on blood transfusion data suggest a beneficial effect of fibrinogen concentrate in reducing the incidence of allogenic transfusions (RR 0.47, 95% CI 0.31 to 0.72) but show no effect on other predefined outcomes, including adverse events such as thrombotic episodes. AUTHORS' CONCLUSIONS: In the six available RCTs of elective surgery, fibrinogen concentrate appears to reduce transfusion requirements, but the included trials are of low quality with high risk of bias and are underpowered to detect mortality, benefit or harm. Furthermore, data on mortality are lacking, heterogeneity is high and acute or severe bleeding in a non-elective surgical setting remains unexplored. Currently, weak evidence supports the use of fibrinogen concentrate in bleeding patients, as tested here in primarily elective cardiac surgery. More research is urgently needed.

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

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

[Hyperfibrinolysis as the cause of haemorrhage and increased mortality in trauma patients]. / Hyperfibrinolyse som årsag til blødning og øget mortalitet hos traumepatienter.

Trauma-associated coagulopathies are at times present upon arrival at the emergency department. Hyperfibrinolysis is a condition in which the natural ability to dissolve blood clots is pathologically enhanced. It is present in 2-8% of trauma patients and associated with shock and increased mortality. Hyperfibrinolysis is easily detected by thromboelastography. The condition is treated with antifibrinolytics such as tranexamic acid--whereas transfusion with blood products is inefficient. This article explores the mechanisms and diagnostics of hyperfibrinolysis in trauma patients and the relevant treatment options.

Thrombelastography (TEG) or thromboelastometry (ROTEM) to monitor haemotherapy versus usual care in patients with massive transfusion.

BACKGROUND: Severe bleeding and coagulopathy as a result of massive transfusion are serious clinical conditions that are associated with high mortality. Thromboelastography (TEG) and thromboelastometry (ROTEM) are increasingly used to guide transfusion strategy but their roles remain disputed. OBJECTIVES: To systematically assess the benefits and harms of a TEG or ROTEM guided transfusion strategy in randomized trials involving patients with severe bleeding. SEARCH STRATEGY: Randomized clinical trials (RCTs) were identified from electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 9); MEDLINE; EMBASE; Science Citation Index Expanded; International Web of Science; CINAHL; LILACS; and the Chinese Biomedical Literature Database (up to 31st October 2010). We contacted trial authors, authors of previous reviews, and manufacturers in the field. SELECTION CRITERIA: We included all RCTs, irrespective of blinding or language, that compared transfusion guided by TEG or ROTEM to transfusion guided by clinical judgement and standard laboratory tests, or both. DATA COLLECTION AND ANALYSIS: Two authors independently abstracted data; they resolved any disagreements by discussion. We presented pooled estimates of the intervention effects on dichotomous outcomes as relative risks (RR) and on continuous outcomes as mean differences, with 95% confidence intervals (CI). Our primary outcome measure was all cause mortality. We performed subgroup and sensitivity analyses to assess the effect of TEG or ROTEM in adults and children on various clinical and physiological outcomes. We assessed the risk of bias through assessment of trial methodological components and the risk of random error through trial sequential analysis. MAIN RESULTS: We included nine RCTs with a total of 776 participants; only one trial had a low risk of bias. We found two ongoing trials but were unable to retrieve any data from them. Compared with standard treatment, TEG or ROTEM showed no statistically significant effect on overall mortality (3.78% versus 5.11%, RR 0.77, 95% CI 0.35 to 1.72; I(2) = 0%) but only five trials provided data on mortality. Our analyses demonstrated a statistically significant effect of TEG or ROTEM on the amount of bleeding (MD -85.05 ml, 95% CI -140.68 to -29.42; I(2) = 26%) but failed to show any statistically significant effect on other predefined outcomes. AUTHORS' CONCLUSIONS: There is an absence of evidence that TEG or ROTEM improves morbidity or mortality in patients with severe bleeding. Application of a TEG or ROTEM guided transfusion strategy seems to reduce the amount of bleeding but whether this has implications for the clinical condition of patients is still uncertain. More research is needed.