Achieving balanced transfusion early in critically bleeding trauma patients: an observational study exploring the effect of attending trauma surgical presence during resuscitation.

Background: After 15 years of damage control resuscitation (DCR), studies still report high mortality rates for critically bleeding trauma patients. Adherence to massive hemorrhage protocols (MHPs) based on a 1:1:1 ratio of plasma, platelets, and red blood cells (RBCs) as part of DCR has been shown to improve outcomes. We wanted to assess MHP use in the early (6 hours from admission), critical phase of DCR and its impact on mortality. We hypothesized that the presence of an attending trauma surgeon during all MHP activations from 2013 would contribute to improving institutional resuscitation strategies and patient outcomes. Methods: We conducted a retrospective analysis of all trauma patients receiving ≥10 RBCs within 6 hours of admission and included in the institutional trauma registry between 2009 and 2019. The cohort was divided in period 1 (P1): January 2009-August 2013, and period 2 (P2): September 2013-December 2019 for comparison of outcomes. Results: A total of 141 patients were included, 81 in P1 and 60 in P2. Baseline characteristics were similar between the groups for Injury Severity Score, lactate, Glasgow Coma Scale, and base deficit. Patients in P2 received more plasma (16 units vs. 12 units; p<0.01), resulting in a more balanced plasma:RBC ratio (1.00 vs. 0.74; p<0.01), and platelets:RBC ratio (1.11 vs. 0.92; p<0.01). All-cause mortality rates decreased from P1 to P2, at 6 hours (22% to 8%; p=0.03), at 24 hours (36% vs 13%; p<0.01), and at 30 days (48% vs 30%, p=0.03), respectively. A stepwise logistic regression model predicted an OR of 0.27 (95% CI 0.08 to 0.93) for dying when admitted in P2. Conclusions: Achieving balanced transfusion rates at 6 hours, facilitated by the presence of an attending trauma surgeon at all MHP activations, coincided with a reduction in all-cause mortality and hemorrhage-related deaths in massively transfused trauma patients at 6 hours, 24 hours, and 30 days. Level of evidence: IV.

Close to zero preventable in-hospital deaths in pediatric trauma patients - An observational study from a major Scandinavian trauma center.

BACKGROUND: In line with international trends, initial treatment of trauma patients has changed substantially over the last two decades. Although trauma is the leading cause of death and disability in children globally, in-hospital pediatric trauma related mortality is expected to be low in a mature trauma system. To evaluate the performance of a major Scandinavian trauma center we assessed treatment strategies and outcomes in all pediatric trauma patients over a 16-year period. METHODS: A retrospective cohort study of all trauma patients under the age of 18 years admitted to a single institution from 1st of January 2003 to 31st of December 2018. Outcomes for two time periods were compared, 2003-2009 (Period 1; P1) and 2010-2018 (Period 2; P2). Deaths were further analyzed for preventability by the institutional trauma Mortality and Morbidity panel. RESULTS: The study cohort consisted of 3939 patients. A total of 57 patients died resulting in a crude mortality of 1.4%, nearly one quarter of the study cohort (22.6%) was severely injured (Injury Severity Score > 15) and mortality in this group decreased from 9.7% in P1 to 4.1% in P2 (p<0.001). The main cause of death was brain injury in both periods, and 55 of 57 deaths were deemed non-preventable. The rate of emergency surgical procedures performed in the emergency department (ED) decreased during the study period. None of the 11 ED thoracotomies in non-survivors were performed after 2013. CONCLUSION: A dedicated multidisciplinary trauma service with ongoing quality improvement efforts secured a low in-hospital mortality among severely injured children and a decrease in futile care. Deaths were shown to be almost exclusively non-preventable, pointing to the necessity of prioritizing prevention strategies to further decrease pediatric trauma related mortality.

Thrombelastography (TEG® 6s) early amplitudes predict maximum amplitude in severely injured trauma patients.

Severely injured trauma patients are often coagulopathic and early hemostatic resuscitation is essential. Previous studies have revealed linear relationships between thrombelastography (TEG®) five- and ten-min amplitudes (A5 and A10), and maximum amplitude (MA), using TEG® 5000 technology. We aimed to investigate the performance of A5 and A10 in predicting low MA in severely injured trauma patients and identify optimal cut-off values for hemostatic intervention based on early amplitudes, using the cartridge-based TEG® 6s technology. Adult trauma patients with hemorrhagic shock were included in the iTACTIC randomized controlled trial at six European Level I trauma centers between 2016 and 2018. After admission, patients were randomized to hemostatic therapy guided by conventional coagulation tests (CCT) or viscoelastic hemostatic assays (VHA). Patients with available admission-TEG® 6s data were included in the analysis, regardless of treatment allocation. Low MA was defined as <55 mm for Kaolin TEG® and RapidTEG®, and <17 mm for TEG® functional fibrinogen (FF). One hundred eighty-seven patients were included. Median time to MA was 20 (Kaolin TEG®), 21 (RapidTEG®) and 12 (TEG® FF) min. For Kaolin TEG®, the optimal Youden index (YI) was at A5 < 36 mm (100/93% sensitivity/specificity) and A10 < 47 mm (100/96% sensitivity/specificity). RapidTEG® optimal YI was at A5 < 34 mm (98/92% sensitivity/specificity) and A10 < 45 mm (96/95% sensitivity/specificity). TEG® FF optimal YI was at A5 < 12 mm (97/93% sensitivity/specificity) and A10 < 15 mm (97/99% sensitivity/specificity). In summary, we found that TEG® 6s early amplitudes were sensitive and specific predictors of MA in severely injured trauma patients. Intervening on early amplitudes can save valuable time in hemostatic resuscitation.

Towards patient-specific management of trauma hemorrhage: the effect of resuscitation therapy on parameters of thromboelastometry.

Essentials The response of thromboelastometry (ROTEM) parameters to therapy is unknown. We prospectively recruited hemorrhaging trauma patients in six level-1 trauma centres in Europe. Blood products and pro-coagulants prevent further derangement of ROTEM results. ROTEM algorithms can be used to treat and monitor trauma induced coagulopathy. SUMMARY: Background Rotational thromboelastometry (ROTEM) can detect trauma-induced coagulopathy (TIC) and is used in transfusion algorithms. The response of ROTEM to transfusion therapy is unknown. Objectives To determine the response of ROTEM profiles to therapy in bleeding trauma patients. Patients/Methods A prospective multicenter study in bleeding trauma patients (receiving ≥ 4 red blood cell [RBC] units) was performed. Blood was drawn in the emergency department, after administration of 4, 8 and 12 RBC units and 24 h post-injury. The response of ROTEM to plasma, platelets (PLTs), tranexamic acid (TXA) and fibrinogen products was evaluated in the whole cohort as well as in the subgroup of patients with ROTEM values indicative of TIC. Results Three hundred and nine bleeding and shocked patients were included. A mean dose of 3.8 g of fibrinogen increased FIBTEM CA5 by 5.2 mm (IQR: 4.1-6.3 mm). TXA administration decreased lysis by 5.4% (4.3-6.5%). PLT transfusion prevented further derangement of parameters of clot formation. The effect of PLTs on EXTEM ca5 values was more pronounced in patients with a ROTEM value indicative of TIC than in the whole cohort. Plasma transfusion decreased EXTEM clotting time by 3.1 s (- 10 s to 3.9 s) in the whole cohort and by 10.6 s (- 45 s to 24 s) in the subgroup of patients with a ROTEM value indicative of TIC. Conclusion The effects of therapy on ROTEM values were small, but prevented further derangement of test results. In patients with ROTEM values indicative of TIC, the efficacy of PLTs and plasma in correcting deranged ROTEM parameters is possibly more robust.

Data-driven Development of ROTEM and TEG Algorithms for the Management of Trauma Hemorrhage: A Prospective Observational Multicenter Study.

OBJECTIVE: Developing pragmatic data-driven algorithms for management of trauma induced coagulopathy (TIC) during trauma hemorrhage for viscoelastic hemostatic assays (VHAs). BACKGROUND: Admission data from conventional coagulation tests (CCT), rotational thrombelastometry (ROTEM) and thrombelastography (TEG) were collected prospectively at 6 European trauma centers during 2008 to 2013. METHODS: To identify significant VHA parameters capable of detecting TIC (defined as INR > 1.2), hypofibrinogenemia (< 2.0 g/L), and thrombocytopenia (< 100 x10/L), univariate regression models were constructed. Area under the curve (AUC) was calculated, and threshold values for TEG and ROTEM parameters with 70% sensitivity were included in the algorithms. RESULTS: A total of, 2287 adult trauma patients (ROTEM: 2019 and TEG: 968) were enrolled. FIBTEM clot amplitude at 5 minutes (CA5) had the largest AUC and 10 mm detected hypofibrinogenemia with 70% sensitivity. The corresponding value for functional fibrinogen (FF) TEG maximum amplitude (MA) was 19 mm. Thrombocytopenia was similarly detected using the calculated threshold EXTEM-FIBTEM CA5 30 mm. The corresponding rTEG-FF TEG MA was 46 mm. TIC was identified by EXTEM CA5 41 mm, rTEG MA 64 mm (80% sensitivity). For hyperfibrinolysis, we examined the relationship between viscoelastic lysis parameters and clinical outcomes, with resulting threshold values of 85% for EXTEM Li30 and 10% for rTEG Ly30.Based on these analyses, we constructed algorithms for ROTEM, TEG, and CCTs to be used in addition to ratio driven transfusion and tranexamic acid. CONCLUSIONS: We describe a systematic approach to define threshold parameters for ROTEM and TEG. These parameters were incorporated into algorithms to support data-driven adjustments of resuscitation with therapeutics, to optimize damage control resuscitation practice in trauma.

iTACTIC - implementing Treatment Algorithms for the Correction of Trauma-Induced Coagulopathy: study protocol for a multicentre, randomised controlled trial.

BACKGROUND: Traumatic injury is the fourth leading cause of death globally. Half of all trauma deaths are due to bleeding and most of these will occur within 6 h of injury. Haemorrhagic shock following injury has been shown to induce a clotting dysfunction within minutes, and this early trauma-induced coagulopathy (TIC) may exacerbate bleeding and is associated with higher mortality and morbidity. In spite of improved resuscitation strategies over the last decade, current transfusion therapy still fails to correct TIC during ongoing haemorrhage and evidence for the optimal management of bleeding trauma patients is lacking. Recent publications describe increasing the use of Viscoelastic Haemostatic Assays (VHAs) in trauma haemorrhage; however, there is insufficient evidence to support their superiority to conventional coagulation tests (CCTs). METHODS/DESIGN: This multicentre, randomised controlled study will compare the haemostatic effect of an evidence-based VHA-guided versus an optimised CCT-guided transfusion algorithm in haemorrhaging trauma patients. A total of 392 adult trauma patients will be enrolled at major trauma centres. Participants will be eligible if they present with clinical signs of haemorrhagic shock, activate the local massive haemorrhage protocol and initiate first blood transfusion. Enrolled patients will be block randomised per centre to either VHA-guided or CCT-guided transfusion therapy in addition to that therapy delivered as part of standard care, until haemostasis is achieved. Patients will be followed until discharge or 28 days. The primary endpoint is the proportion of subjects alive and free of massive transfusion (less than 10 units of red blood cells) at 24 h. Secondary outcomes include the effect of CCT- versus VHA-guided therapy on organ failure, total hospital and intensive care lengths of stay, health care resources needed and mortality. Surviving patients will be asked to complete a quality of life questionnaire (EuroQol EQ-5DTM) at day 90. DISCUSSION: CCTs have traditionally been used to detect TIC and monitor response to treatment in traumatic major haemorrhage. The use of VHAs is increasing, but limited evidence exists to support the superiority of these technologies (or comparatively) for patient-centred outcomes. This knowledge gap will be addressed by this trial. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02593877 . Registered on 15 October 2015. Trial sponsor Queen Mary University of London The contact person of the above sponsor organisation is: Dr. Sally Burtles, Director of Research Services and Business Development, Joint Research Management Office, QM Innovation Building, 5 Walden Street, London E1 2EF; phone: 020 7882 7260; Email: sponsorsrep@bartshealth.nhs.uk Trial sites Academic Medical Centre, Amsterdam, The Netherlands Kliniken der Stadt Köln gGmbH, Cologne, Germany Rigshospitalet (Copenhagen University Hospital), Copenhagen, Denmark John Radcliff Hospital, Oxford, United Kingdom Oslo University Hospital, Oslo, Norway The Royal London Hospital, London, United Kingdom Centre for Trauma Sciences, Blizard Institute, Queen Mary University of London, London, United Kingdom Health Economics Research Centre, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom Sites that are planning to start recruitment in mid/late 2017 Nottingham University Hospitals, Queen's Medical Centre, Nottingham, United Kingdom University of Kansas Hospital (UKH), Kansas City, MO, USA Protocol version: 3.0/14.03.2017 (Additional file 1).