Protocol for a systematic review of the clinical effectiveness of pre-hospital blood components compared to other resuscitative fluids in patients with major traumatic haemorrhage

BACKGROUND: There is growing interest in the use of blood components for pre-hospital resuscitation of patients with major traumatic haemorrhage. It has been speculated that early resuscitation with blood components may have benefits in terms of treating trauma-induced coagulopathy, which in turn may influence survival. The proposed systematic review will evaluate the evidence on the clinical effectiveness of pre-hospital blood components (red blood cells and/or plasma or whole blood), in both civilian and military settings, compared with other resuscitation strategies in patients with major traumatic haemorrhage. METHODS/DESIGN: Standard systematic review methods aimed at minimising bias will be employed for study identification, selection and data extraction. General medical and specialist databases will be searched; the search strategy will combine terms for the population, intervention and setting. Studies will be selected for review if the population includes adult patients with major traumatic haemorrhage who receive blood components in a pre-hospital setting (civilian or military). Systematic reviews, randomised and non-randomised controlled trials and controlled observational studies will be included. Uncontrolled studies will be considered depending on the volume of controlled evidence. Quality assessment will be tailored to different study designs. Both patient related and surrogate outcomes will be considered. Synthesis is likely to be primarily narrative, but meta-analyses and subgroup analyses will be undertaken where clinical and methodological homogeneity exists. DISCUSSION: Given the increasing use by emergency services of blood components for pre-hospital resuscitation, this is a timely systematic review, which will attempt to clarify the evidence base for this practice. As far as the authors are aware, the proposed systematic review will be the first to address this topic. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD4201401379

Resuscitation with pre-hospital blood products in adults with trauma-related haemorrhagic shock:the RePHILL RCT

Background: The treatment of traumatic haemorrhagic shock has been transformed through better haemorrhage control, use of tranexamic acid and use of blood products. The improved survival seen from these strategies has stimulated an interest in pre-hospital transfusion.Objectives: To determine if the clinical effectiveness of resuscitation with red blood cells and lyophilised plasma was superior to 0.9% saline for improving tissue perfusion and reducing mortality in adults with haemorrhagic shock following major trauma.Design: A multi-centre, allocation concealed, open-label, parallel group, randomised controlled trial (with internal pilot).Setting: The trial was conducted in four civilian pre-hospital critical care services who operated within the National Health Service (NHS) England Major Trauma Networks.Participants: Adults (aged ≥16 years) who had sustained traumatic injuries, were attended by a pre-hospital emergency medical team and were hypotensive (systolic blood pressure &lt;90 mmHg or absence of radial pulse) as a consequence of traumatic haemorrhage were eligible for inclusion. The exclusion criteria were known or apparently &lt;16 years, blood administered on scene prior to the arrival of the RePHILL team, traumatic cardiac arrest where (1) the arrest occurred prior to arrival of the team and/or (2) the primary cause is not hypovolaemia, refusal of blood product administration, known Jehovah’s Witness, pregnancy, isolated head injury without evidence of external haemorrhage, prisoners in the custody of HM Prison and Probation Service.Interventions: Participants were randomised to receive up to either two units each of red blood cells and lyophilised plasma or up to 1 L 0.9% saline. Treatment was administered through the intravenous or intraosseous route.Main outcome measures: The primary outcome was a composite of episode mortality and/or impaired lactate clearance. The secondary outcomes included the individual components of the primary outcome.Results: From 6 December 2016 to 2 January 2021, pre-hospital medical teams randomised 432 participants to red blood cell/lyophilised plasma (n = 209) or 0.9% saline (n = 223) out of a target sample size of 490. Most participants were white (62%), males (82%), median age 38 (interquartile range 26 to 58), involved in a road traffic collision (62%) with severe injuries (median injury severity score 36, interquartile range 25 to 50). Prior to randomisation participants had received on average 430 ml crystalloid fluids and tranexamic acid (90%). The primary outcome occurred in 128/199 (64.3%) of participants randomised to red blood cell/lyophilised plasma and 136/210 (64.8%) randomised to 0.9% saline [adjusted risk difference –0.025% (95% confidence interval –9.0% to 9.0%), p = 0.996]. The event rates for the individual components of the primary outcome, episode mortality and lactate clearance were not statistically different between groups [adjusted average differences −3% (−12% to 7%); p = 0.57 and −5% (−14% to 5%), p = 0.33, respectively].Limitations: Recruitment stopped prematurely due to disruption caused by the COVID-19 pandemic.Future work: Identify the characteristics of patients who may benefit from pre-hospital blood products and whether alternative transfusion regimens are superior to standard care.Conclusions: The trial did not demonstrate that pre-hospital red blood cell/lyophilised plasma resuscitation was superior to 0.9% saline for trauma-related haemorrhagic shock.Trial registration: This trial is registered as ISRCTN62326938.Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation Programme (NIHR award ref: 14/152/14) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 2. See the NIHR Funding and Awards website for further award information.<br/

Mapping the Steroid Response to Major Trauma From Injury to Recovery : A Prospective Cohort Study

CONTEXT: Survival rates after severe injury are improving, but complication rates and outcomes are variable. OBJECTIVE: This cohort study addressed the lack of longitudinal data on the steroid response to major trauma and during recovery. DESIGN: We undertook a prospective, observational cohort study from time of injury to 6 months postinjury at a major UK trauma centre and a military rehabilitation unit, studying patients within 24 hours of major trauma (estimated New Injury Severity Score (NISS) > 15). MAIN OUTCOME MEASURES: We measured adrenal and gonadal steroids in serum and 24-hour urine by mass spectrometry, assessed muscle loss by ultrasound and nitrogen excretion, and recorded clinical outcomes (ventilator days, length of hospital stay, opioid use, incidence of organ dysfunction, and sepsis); results were analyzed by generalized mixed-effect linear models. FINDINGS: We screened 996 multiple injured adults, approached 106, and recruited 95 eligible patients; 87 survived. We analyzed all male survivors <50 years not treated with steroids (N = 60; median age 27 [interquartile range 24-31] years; median NISS 34 [29-44]). Urinary nitrogen excretion and muscle loss peaked after 1 and 6 weeks, respectively. Serum testosterone, dehydroepiandrosterone, and dehydroepiandrosterone sulfate decreased immediately after trauma and took 2, 4, and more than 6 months, respectively, to recover; opioid treatment delayed dehydroepiandrosterone recovery in a dose-dependent fashion. Androgens and precursors correlated with SOFA score and probability of sepsis. CONCLUSION: The catabolic response to severe injury was accompanied by acute and sustained androgen suppression. Whether androgen supplementation improves health outcomes after major trauma requires further investigation

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Immunology of transplantation

Understanding the interaction of foreign tissue with the recipient immune system is key to improving results from organ transplantation. Responses are mediated by the humoral and cellular arms of the host immune system towards the tissues of the transplant. Unchecked this can lead to rejection of the graft. Improvements in immunosuppressive therapy have countered these reactions to a degree but are not without side effects. Future work is directed at improving graft tolerance without unwanted host effects

The immune system

The immune system provides the body with both non-specific and specific defence against pathogens. It can recognize foreign from self. The immune system is composed of lines of defence and can mount responses by cellular and humoral mechanisms. It also has memory, allowing a quicker and heightened response on subsequent exposure. It achieves these effects by a complex interaction between the clotting, complement and kinin systems, endothelial cells and the cells and proteins of the immune system

Feasibility of using rotational thromboelastometry to assess coagulation status of combat casualties in a deployed setting

Background: Coagulopathy in trauma patients is currently defined by the results of standard laboratory tests (prothrombin time and activated partial thromboplastin time). These results offer little in the hemostatic resuscitation that occurs in the treatment of battlefield patients who receive massive transfusions. Thromboelastometry (TEM) is a technique that can offer rapid, near-patient testing of coagulation status. Methods: A prospective observational field study was performed in a deployed military setting to determine the feasibility of using TEM to assess the coagulation status of patients admitted to the emergency department and who subsequently received a massive transfusion. Results: TEM was performed on 31 patients, 25 were direct admissions to the emergency department, 19 of whom were enrolled into the massive transfusion protocol, and 60% were involved in a blast incident. Standard laboratory testing showed that 10% of all patients were coagulopathic on admission compared with 64% with an abnormal TEM trace (p = 0.0005). All patients had abnormal maximum clot firmness. The TEM amplitude at 10 minutes is associated with the subsequent development of abnormal maximum clot firmness. Two exemplar cases are discussed, which illustrate the potential benefit of using TEM to monitor and guide and individualize therapy during a massive transfusion. Conclusions: It is feasible to use TEM in a deployed military setting. We have shown that rotational thromboelastometry significantly detects more abnormalities in the coagulation status than the standard laboratory tests (prothrombin time, and activated partial thromboplastin time)

Radiographic assessment of sarcopenia in the trauma setting: a systematic review

Background Compared with similarly injured patients of a younger age, elderly patients have worse outcomes from acute injury. One factor adversely affecting outcomes is sarcopenia, which has been assessed in healthy elderly populations through established clinical and radiological criteria. However, in the acute care setting, no such criteria have been established. Sarcopenia has been opportunistically assessed via radiographic means but there is as of yet no gold standard. The purpose of this review is to summarize the radiological methods used to diagnose sarcopenia in the acute care setting, and suggest ways in which these methods may lead to a consensus definition of sarcopenia and its relationship to patient outcomes. Methods A systematic survey of medical databases was conducted, with 902 unique publications identified. After screening and application of inclusion and exclusion criteria, data regarding study population, outcome, imaging modality, and criteria for assessment of sarcopenia were extracted from 20 studies. Quality was assessed with the Newcastle-Ottawa Scale. Results CT was the imaging modality for 18 of the studies, with total psoas muscle cross-sectional area at the level of L3 and L4 being the dominant method for assessing sarcopenia. Adjustment for body morphology most commonly used patient height or L4 vertebral body area. The majority of articles found radiographically assessed sarcopenia to be significantly correlated to outcomes such as mortality, length of hospital stay, morbidity, and in-hospital complications Conclusions Establishing a consistent definition would strengthen its applicability and generalizability to admission and discharge planning. Level of evidence Systematic review, level III