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/

Appropriation of GPIb from platelet-derived extracellular vesicles supports monocyte recruitment in systemic inflammation

Interactions between platelets, leukocytes and the vessel wall provide alternative pathological routes of thrombo-inflammatory leukocyte recruitment. We found that when platelets were activated by a range of agonists in whole blood, they shed platelet-derived extracellular vesicles which rapidly and preferentially bound to blood monocytes compared to other leukocytes. Platelet-derived extracellular vesicle binding to monocytes was initiated by P-selectin-dependent adhesion and was stabilised by binding of phosphatidylserine. These interactions resulted in the progressive transfer of the platelet adhesion receptor GPIbα to monocytes. GPIbα+-monocytes tethered and rolled on immobilised von Willebrand Factor or were recruited and activated on endothelial cells treated with TGF-β1 to induce the expression of von Willebrand Factor. In both models monocyte adhesion was ablated by a function-blocking antibody against GPIbα. Monocytes could also bind platelet-derived extracellular vesicle in mouse blood in vitro and in vivo. Intratracheal instillations of diesel nanoparticles, to model chronic pulmonary inflammation, induced accumulation of GPIbα on circulating monocytes. In intravital experiments, GPIbα+-monocytes adhered to the microcirculation of the TGF-β1-stimulated cremaster muscle, while in the ApoE−/− model of atherosclerosis, GPIbα+-monocytes adhered to the carotid arteries. In trauma patients, monocytes bore platelet markers within 1 hour of injury, the levels of which correlated with severity of trauma and resulted in monocyte clearance from the circulation. Thus, we have defined a novel thrombo-inflammatory pathway in which platelet-derived extracellular vesicles transfer a platelet adhesion receptor to monocytes, allowing their recruitment in large and small blood vessels, and which is likely to be pathogenic

Prehospital use of ketamine for analgesia and procedural sedation by critical care paramedics in the UK: a note of caution?

Extended skills for critical care paramedics (CCPs) in UK based systems have been extensively evaluated in recent times.1 ,2 Autonomous administration of ketamine for analgesia and conscious sedation has been identified as a core skill for CCPs but concerns have been raised about the level of exposure required to maintain competence.3 To date there have been no reports in the literature detailing the experience of ketamine administration by CCPs in the UK

Prehospital rapid sequence induction following trauma in the era of regional networks for major trauma

Objective Rapid sequence induction (RSI) provides prompt airway control during emergency evacuation of trauma patients. Physicians may be tasked to travel with paramedic ambulance crews to the scene of injury when RSI is more likely to be required. This study investigates whether there are any differences in the practice of prehospital RSI during emergency retrievals for trauma since the establishment of the regional Major Trauma Network (MTN) in March 2012.Methods A retrospective observational study examined prehospital records for all trauma patients from September 2010 to January 2015 at a Major Trauma Centre in Birmingham, UK. Prehospital physician availability increased from 12 to 24 h after March 2012, and tasking became centralized. Data included demographics, mechanism of injury, crew personnel, and details of RSI. The periods before and after the establishment of the regional MTN were compared.Results There were 5244 patients: 1432 (27.3%) before and 3812 (72.7%) after March 2012. Of the patients, 67.2% were male. The most common injuries were road traffic collisions (45.0%). Physicians were more likely to be present after (2345 missions, 61.5%) than before (529 missions, 36.9%) March 2012 (

'Interception': a model for specialist prehospital care provision when helicopters are not available.

The deployment of specialist teams to incident scenes by helicopter and the delivery of critical care interventions such as Rapid Sequence Induction of anaesthesia to patients are becoming well-established components of trauma care in the UK. Traditionally in the UK, Helicopter Emergency Medical Services (HEMS) are limited to daylight operations only. The safety and feasibility of operating HEMS services at night is a topic of debate currently in the UK HEMS community. Within the West Midlands Major Trauma Network, the Medical Emergency Response Incident Team (MERIT) provides a physician-led prehospital care service that responds to incidents by air during daylight hours and by Rapid Response Vehicle during the hours of darkness. The MERIT service is coordinated and supported by a dedicated Major Trauma Desk manned by a HEMS paramedic in the ambulance service control room. This case illustrates the importance of coordination and integration of specialist resources within a major trauma network to ensure the expedient delivery of HEMS-level care to patients outside of normal flying hours

What fluids are given during air ambulance treatment of patients with trauma in the UK, and what might this mean for the future? Results from the RESCUER observational cohort study

Objectives: We investigated how often intravenous fluids have been delivered during physician-led prehospital treatment of patients with hypotensive trauma in the UK and which fluids were given. These data were used to estimate the potential national requirement for prehospital blood products (PHBP) if evidence from ongoing trials were to report clinical superiority. Setting: The Regional Exploration of Standard Care during Evacuation Resuscitation (RESCUER) retrospective observational study was a collaboration between 11 UK air ambulance services. Each was invited to provide up to 5 years of data and total number of taskings during the same period. Participants: Patients with hypotensive trauma (systolic blood pressure <90 inm Hg or absent radial pulse) attended by a doctor. Primary and secondary outcome measures: The primary outcome was the number of patients with hypotensive trauma given prehospital fluids. Secondary outcomes were types and volumes of fluids. These data were combined with published data to estimate potential national eligibility for PHBP. Results: Of 29037 taskings, 729 (2.5%) were for patients with hypotensive trauma attended by a physician. Half were aged 21-50 years; 73.4% were male. A total of 537 out of 729 (73.7%) were given fluids. Five hundred and ten patients were given a single type of fluid; 27 received >1 type. The most common fluid was 0.9% saline, given to 486/537 (90.5%) of patients who received fluids, at a median volume of 750 (IQR 300-1500)mL. Three per cent of patients received PHBP. Estimated projections for patients eligible for PHBP at these 11 services and in the whole UK were 313 and 794 patients per year, respectively. Conclusions: One in 40 air ambulance taskings were manned by physicians to retrievepatients with hypotensive trauma. The most common fluid delivered was 0.9% saline. If evidence justifies universal provision of PHBP, approximately 800 patients/year would be eligible in the UK, based on our data combined with others published. Prospective investigations are required to confirm or adjust these estimations