Massive transfusion in trauma.

PURPOSE OF REVIEW: The purpose of this review is to provide an overview of currently recommended treatment approaches for traumatic hemorrhage shock, with a special focus on massive transfusion. RECENT FINDINGS: Severe trauma patients require massive transfusion, but consensual international definitions for traumatic hemorrhage shock and massive transfusion are missing. Current literature defines a massive transfusion as transfusion of a minimum of 3-4 packed red blood cells within 1 h. Using standard laboratory and/or viscoelastic tests, earliest diagnosis and treatment should focus on trauma-induced coagulopathy and substitution of substantiated deficiencies. SUMMARY: To initiate therapy immediately massive transfusion protocols are helpful focusing on early hemorrhage control using hemostatic dressing and tourniquets, correction of metabolic derangements to decrease coagulopathy and substitution according to viscoelastic assays and blood gases analysis with tranexamic acid, fibrinogen concentrate, red blood cells, plasma and platelets are recommended. Alternatively, the use of whole blood is possible. If needed, further support using prothrombin complex, factor XIII or desmopressin is suggested.

Indications for the Use of Therapeutic Plasma in Adult Patients.

Background: Different preparations for therapeutic plasma are available on the market. The German hemotherapy guideline has been completely updated in 2020 and, for this purpose, has reviewed the evidence for the most frequent clinical indications for the use of therapeutic plasma in adult patients. Summary: The German hemotherapy guideline has reviewed the evidence for the following indications for the use of therapeutic plasma in the adult patient: massive transfusion and bleeding, severe chronic liver disease, disseminated intravascular coagulation, plasma exchange for TTP, and the rare hereditary FV and FXI deficiencies. The updated recommendations for each indication are discussed on the background of existing guidelines and new evidence. For most indications, the quality of evidence is low due to missing prospective randomized trials or rare diseases. However, due to the "balanced" content of coagulation factors and inhibitors therapeutic plasma remains an important pharmacological treatment option in clinical situations with an already activated coagulation system. Unfortunately, the "physiological" content of coagulation factors and inhibitors limits the efficacy in clinical scenarios with high blood losses. Key Messages: The evidence for the use of therapeutic plasma for the replacement of coagulation factors due to massive bleeding is poor. Coagulation factor concentrates seem to be more appropriate for this indication, although the quality of evidence is also low. However, for diseases with an activated coagulation or endothelial system (e.g., disseminated intravascular coagulation, TTP) the balanced replacement of coagulation factors, inhibitors, and proteases may be of advantage.

Peripartum Haemorrhage: Haemostatic Aspects of the Updated Peripartum Haemorrhage Guideline of the German-Speaking Countries.

Background: Peripartum haemorrhage (PPH) is a potentially life-threatening complication. Although still rare, the incidence of peripartal haemorrhage is rising in industrialised countries and refractory bleeding remains among the leading causes of death in the peripartal period. Summary: The interdisciplinary German, Austrian, and Swiss guideline on "Peripartum Haemorrhage: Diagnostics and Therapies" has reviewed the evidence for the diagnostics and medical, angiographic, haemostatic, and surgical treatment and published an update in September 2022 . This article reviews the updated recommendations regarding the early diagnosis and haemostatic treatment of PPH. Keystones of the guideline recommendations are the early diagnosis of the bleeding by measuring blood loss using calibrated collector bags, the development of a multidisciplinary treatment algorithm adapted to the severity of bleeding, and the given infrastructural conditions of each obstetric unit, the early and escalating use of uterotonics, the therapeutic, instead of preventative, use of tranexamic acid, the early diagnostics of progressive deficiencies of coagulation factors or platelets to facilitate a tailored and guided haemostatic treatment with coagulation factors, platelets as well as packed red blood cells and fresh frozen plasma when a massive transfusion is required. Key Messages: Essential for the effective and safe treatment of PPH is the timely diagnosis. The diagnosis of PPH requires the measurement rather than estimation of blood loss. Successful treatment of PPH consists of a multidisciplinary approach involving surgical and haemostatic treatments to stop the bleeding. Haemostatic treatment of PPH starts early after diagnosis and combines tranexamic acid, an initially ratio-driven transfusion with RBC:plasma:PC = 4:4:1 (when using pooled or apheresis PC) and finally a goal-directed substitution with coagulation factor concentrates for proven deficiencies. Early monitoring of coagulation either by standard parameters or viscoelastic methods facilitates goal-directed haemostatic treatment.

Emergency Blood Transfusion for Trauma and Perioperative Resuscitation: Standard of Care.

Uncontrolled and massive bleeding with derangement of coagulation is a major challenge in the management of both surgical and seriously injured patients. The underlying mechanism of trauma-induced or -associated coagulopathy is tissue injury in the presence of shock and acidosis provoking endothelial damage, activation of inflammation, and coagulation disbalancing. Furthermore, the combination of ongoing blood loss and consumption of blood components that are essential for effective coagulation worsens uncontrolled hemorrhage. Additionally, therapeutic actions, such as resuscitation with replacement fluids or allogeneic blood products, can further aggravate coagulopathy. Of the coagulation factors essential to the clotting process, fibrinogen is the first to be consumed to critical levels during acute bleeding and current evidence suggests that normalizing fibrinogen levels in bleeding patients improves clot formation and clot strength, thereby controlling hemorrhage. Three different therapeutic approaches are discussed controversially. Whole blood transfusion is used especially in the military scenario and is also becoming more and more popular in the civilian world, although it is accompanied by a strong lack of evidence and severe safety issues. Transfusion of allogeneic blood concentrates in fixed ratios without any targets has been investigated extensively with disappointing results. Individualized and target-controlled coagulation management based on point-of-care diagnostics with respect to the huge heterogeneity of massive bleeding situations is an alternative and advanced approach to managing coagulopathy associated with massive bleeding in the trauma as well as the perioperative setting.

Tranexamic Acid for Acute Hemorrhage: A Narrative Review of Landmark Studies and a Critical Reappraisal of Its Use Over the Last Decade.

The publication of the Clinical Randomization of an Antifibrinolytic in Significant Hemorrhage-2 (CRASH-2) study and its intense dissemination prompted a renaissance for the use of the antifibrinolytic agent tranexamic acid (TXA) in acute trauma hemorrhage. Subsequent studies led to its widespread use as a therapeutic as well as prophylactic agent across different clinical scenarios involving bleeding, such as trauma, postpartum, and orthopedic surgery. However, results from the existing studies are confounded by methodological and statistical ambiguities and are open to varied interpretations. Substantial knowledge gaps remain on dosing, pharmacokinetics, mechanism of action, and clinical applications for TXA. The risk for potential thromboembolic complications with the use of TXA must be balanced against its clinical benefits. The present article aims to provide a critical reappraisal of TXA use over the last decade and a "thought exercise" in the potential downsides of TXA. A more selective and individualized use of TXA, guided by extended and functional coagulation assays, is advocated in the context of the evolving concept of precision medicine.

Peripartum Haemorrhage: Haemostatic Aspects of the New German PPH Guideline.

Summary Peripartum haemorrhage remains one of the main causes of maternal mortality world-wide. The German, Austrian and Swiss Societies of Gynaecology and Obstetrics have updated the current guidelines for the treatment of peripartum haemorrhage together with the German Society of Anaesthesiology and Intensive Care Medicine and the Society of Thrombosis and Haemostasis Research. The recommendations have been the result of a thorough review of the available scientific literature and a consensus process involving all members of the guideline group. A key element of the anaesthesiological and haemostatic management is the development of a multidisciplinary standard operating procedure combining surgical as well as medical and haemostatic treatments depending on the severity of bleeding. The guideline underscores the value of clinical and laboratory diagnostics of peripartum haemorrhage as early as possible, even pre-emptively. This allows for an early identification of causes of bleeding and a specific treatment. The guideline comprises evidence-based recommendations for the use of uterotonics, tranexamic acid and blood products such as factor concentrates, fresh frozen plasma, platelet concentrates, packed red blood cells, recombinant activated factor VII and desmopressin. In addition, recommendations for blood conservation strategies involving the use of cell salvage, permissive hypotension and transfusion triggers are given.

Prehospital Blood Product Transfusion in Mountain Rescue Operations.

Severely injured patients with hemorrhage present major challenges for emergency medical services, especially during mountain rescue missions in which harsh environmental conditions and long out-of-hospital times are frequent. Because uncontrolled hemorrhage is the leading cause of death within the first 48 hours after severe trauma, initiating damage control resuscitation (DCR) as early as possible after severe trauma and exporting the concept of DCR to the out-of-hospital arena is pivotal for patient survival. Appropriate bleeding control, management of coagulopathy, and transfusion of blood products are core aspects of DCR. This review summarizes the available evidence on out-of-hospital blood product transfusion and the management of coagulopathy with a special focus on mountain rescue missions. An overview of upcoming trials and possible future trends in the management of coagulopathy during rescue operations is provided.

[The new German guideline on postpartum haemorrhage (PPH): essential aspects for coagulation and circulatory therapy]. / Die neue deutsche Leitlinie zur peripartalen Hämorrhagie - Wichtige Aspekte für die Gerinnungs- und Kreislauftherapie.

Worldwide, post-partum haemorrhage (PHH) remains one of the leading causes for maternal mortality. The German Society of Gynaecology and Obstetrics, the German Midwifes' Society, the German Society of Thrombosis and Haemostasis and the German Society of Anaesthesiology and Intensive Care updated the former guideline. The resulting recommendations are the results of a structured literature search and a formal consensus process and contain all aspects of PPH including diagnosis, causes, risk factors and therapy. Key aspect of the anaesthesiological and haemostatic therapies is the development of an interdisciplinary standard operating procedure containing medical options related to the bleeding's cause and severity as well as the surgical option. For suspected PPH, this guideline emphasizes clinical and laboratory-based diagnostics, as only those will enable an early identification of the bleeding's causes and the resulting causative therapy. Recommendations cover evidence-based application of uterotonics for atony as well as tranexamic acid, calcium, factor concentrates and blood products. Additionally, recommendations are given on the topics of cell salvage, controlled hypotension and restrictive transfusion triggers.

Pre-Hospital Blood Products for the Care of Bleeding Trauma Patients.

BACKGROUND: Controversy surrounds the administration of blood products to severely traumatized patients before they arrive in the hospital in order to compensate for early blood loss and/or to correct coagulation disturbances that arise shortly after the traumatic event. A number of terrestrial and air rescue services have begun to provide this kind of treatment. METHODS: This review is based on articles using the PICO framework, published from January 2001 to January 2021, that were retrieved by a selective search, with structured searching strategies and searching bundles in Medline (OVIDSP), the Cochrane Central Register of Controlled Trials (CENTRAL), and Epistemonikos. A demand analysis was carried out on the basis of data from the trauma registry of the German Society of Trauma Surgery (TR-DGU) and practical experience from program development and implementation was provided by the Bundeswehr Hospital Ulm. RESULTS: The currently available evidence on the pre-hospital administration of blood products in the early treatment of severely injured patients is based largely on retrospective, single-center case series. Two randomized controlled trials (RCTs) concerning the early use of fresh frozen plasma concentrates have yielded partly conflicting results. Three further RCTs on the use of lyophilized plasma (lyplas), lyplas plus erythrocyte concentrate, or whole blood likewise revealed non-uniform effects on short-term and intermediate-term mortality. Our demand analysis based on data from the TR-DGU showed that 300 to 1800 patients per year in Germany could benefit from the pre-hospital administration of blood products. This might be indicated in patients who have systolic hypotension (<100 mmHg) in combination with a suspected or confirmed hemorrhage, as well as pathological shock parameters in the point-of-care diagnostic testing performed on the scene (serum base excess ≤ -2.5 mmol/L and/or serum lactate concentration >4 mmol/L). CONCLUSION: The studies that have been published to date yield no clear evidence either for or against the early pre-hospital administration of blood products. Any treatment of this kind should be accompanied by scientific evaluation.

Die perioperative Gabe von Tranexamsäure. / The Perioperative Application of Tranexamic Acid.

The application of tranexamic acid (TXA) during endoprosthetic surgical procedures has significantly increased in recent years. Due its ability to reduce perioperative blood loss and avert the need for blood transfusions as well as wound drainage, TXA is becoming part of a 'standard practice'. However, TXA is currently not approved for the application during endoprosthetic procedures and therefore, a benefit-risk analysis should always be conducted. Prophylactic administration of TXA without prior patient consent is only justified if fibrinolytic bleeding is expected and there are no contraindications or relevant risk factors for thromboembolic complications. Respectively, no patient consent is required when a therapeutic dose of TXA is administered in the context of fibrinolytic bleeding. The following guidelines provide updated recommendations based on the current state of knowledge on TXA optimal timing, routes of administration and dosing regimen.

Preconditions of hemostasis in trauma: a review. The influence of acidosis, hypocalcemia, anemia, and hypothermia on functional hemostasis in trauma.

BACKGROUND: Beside the often discussed topics of consumption and dilution coagulopathy, additional perioperative impairments of coagulation are caused by acidosis, hypocalcemia, anemia, hypothermia, and combinations. METHODS: Reviewing current literature, cutoff values of these parameters become obvious at which therapy should commence. RESULTS: A notable impairment of hemostasis arises at a pH < or = 7.1. Similar effects are caused by a BE of -12.5 or less. Thus, in case of severe bleeding, buffering toward physiologic pH values is recommended, especially with massive transfusions of older RBCCs displaying exhausted red blood cell buffer systems. It completes the optimization of the volume homeostasis to ensure an adequate tissue perfusion. Combining beneficial cardiovascular and coagulation effects, the level for ionized calcium concentration should be held > or = 0.9 mmol/L. From the hemostatic point of view, the optimal Hct is higher than the one required for oxygenation. Even without a "classical" transfusion trigger, the therapy of acute, persistent bleeding should aim at reaching an Hct > or = 30%. A core temperature of < or = 34 degrees C causes a decisive impairment of hemostasis. A controlled hypotensive fluid resuscitation should aim at reaching a mean arterial pressure of > or = 65 mm Hg (possibly higher for cerebral trauma). Prevention and later aggressive therapy of hypothermia by exclusive infusion of warmed fluids and the use of warming devices are prerequisites for the cure of traumatic coagulopathy. Combined appearance of single preconditions cause additive impairments of the coagulation system. CONCLUSIONS: The prevention and timely correction, especially of the combination acidosis plus hypothermia, is crucial for the treatment of hemorrhagic coagulopathy.

Peripartum Haemorrhage, Diagnosis and Therapy. Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Registry No. 015/063, March 2016).

PURPOSE: This is an official interdisciplinary guideline, published and coordinated by the German Society of Gynaecology and Obstetrics (DGGG), the Austrian Society of Gynaecology and Obstetrics (OEGGG) and the Swiss Society of Gynaecology and Obstetrics (SGGG). The guideline was developed for use in German-speaking countries and is backed by the German Society of Anaesthesiology and Intensive Medicine (DGAI), the Society of Thrombosis and Haemostasis Research (GTH) and the German Association of Midwives. The aim is to provide a consensus-based overview of the diagnosis and management of peripartum bleeding obtained from an evaluation of the relevant literature. METHODS: This S2k guideline was developed from the structured consensus of representative members of the various professional associations and professions commissioned by the Guideline Commission of the DGGG. RECOMMENDATIONS: The guideline encompasses recommendations on definitions, risk stratification, prevention and management.

Comparison of different video laryngoscopes for emergency intubation in a standardized airway manikin with immobilized cervical spine by experienced anaesthetists. A randomized, controlled crossover trial.

BACKGROUND: The aim of the present study was to evaluate whether different video laryngoscopes (VLs) facilitate endotracheal intubation (ETI) faster or more secure than conventional laryngoscopy in a manikin with immobilized cervical spine. METHODS: After local ethics board approval, a standard airway manikin with cervical spine immobilization by means of a standard stiff collar was placed on a trauma stretcher. We compared times until glottic view, ETI, cuff block and first ventilation were achieved, and verified the endotracheal tube position, when using Macintosh laryngoscope, Glidescope Ranger, Storz C-MAC, Ambu Pentax AWS, Airtraq, and McGrath Series5 VLs in randomized order. Wilcoxon signed-rank test and McNemar's test were used for statistical analysis; p<0.05 was considered as significant. RESULTS: Twenty-three anaesthetists (mean age 32.1±4.9 years, mean experience in anaesthesia of 6.9±4.8 years) routinely involved in the management of multitrauma patients participated. The primary study end point, time to first effective ventilation, was achieved fastest when using Macintosh laryngoscope (21.0±7.6s) and was significantly slower with all other devices (Airtraq 33.2±23.9 s, p=0.002; Pentax AirwayScope 32.4±14.9 s, p=0.001; Storz C-MAC 34.1±23.9 s, p<0.001; McGrath Series5 101.7±108.3 s, p<0.001; Glidescope Ranger 46.3±59.1 s, p=0.001). Overall success rates were highest when using Macintosh, Airtraq and Storz C-MAC devices (100%), and were lower in Ambu Pentax AWS and Glidescope Ranger (87%, p=0.5) and in McGrath Series5 device (72.2%, p=0.063). CONCLUSION: When used by experienced anaesthesiologists, video laryngoscopes did not facilitate endotracheal intubation in this model with an immobilized cervical spine in a faster or more secure way than conventional laryngoscopy. However, data was gathered in a standardized model and further studies in real trauma patients are desirable to verify our findings.

Coagulation management in multiple trauma: a systematic review.

PURPOSE: The management of trauma patients suffering from active bleeding has improved with a better understanding of trauma-induced coagulopathy. The aim of this manuscript is to give recommendations for coagulation management. METHODS: A systematic literature search in the PubMed database was performed for articles published between January 2000 and August 2009. A total of 230 articles were included in the present systematic review. CONCLUSIONS: The "coagulopathy of trauma" is a discrete disease which has a decisive influence on survival. Diagnosis and therapy of deranged coagulation should start immediately after admission to the emergency department. A specific protocol for massive transfusion should be introduced and continued. Loss of body temperature should be prevented and treated. Acidaemia should be prevented and treated by appropriate shock therapy. If massive transfusion is performed using fresh frozen plasma (FFP), a ratio of FFP to pRBC (packed red blood cells) of 1:2-1:1 should be achieved. Fibrinogen should be substituted at levels of <1.5 g/L. For patients suffering from active bleeding, permissive hypotension (i.e. mean arterial pressure ~65 mmHg) may be aimed for until surgical cessation of bleeding. This option is contraindicated in injuries of the central nervous system and in patients with coronary heart disease, or with known hypertension. Thrombelastography or -metry may be performed to guide coagulation diagnosis and substitution. Hypocalcaemia <0.9 mmol/L should be avoided and may be treated. For actively bleeding patients, pRBC may be given at haemoglobin <10 g/L (6.2 mmol/L) and haematocrit may be targeted at 30%.