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 <90 mmHg or absence of radial pulse) as a consequence of traumatic haemorrhage were eligible for inclusion. The exclusion criteria were known or apparently <16 years, blood administered on scene prior to 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.
Blood and plasma are life-saving treatments for people with severe bleeding following major traumatic injury. Until recently, they could only be administered in hospital. The Resuscitation with Pre-Hospital Blood Products (RePHILL) trial tested whether providing these treatments before the injured person arrives in hospital was better than current NHS treatment (a clear fluid called 0.9% saline).
We worked with NHS ambulance services, air ambulance charities, blood transfusion laboratories, blood bikers and the NHS major trauma networks to make blood and plasma available to patients outside the hospital. Blood banks prepared sealed boxes according to a schedule prepared by the research team. Half the boxes contained blood and plasma (treatment) and half contained salty water (control). The pre-hospital critical care teams did not know what was in the sealed boxes.
Critical care doctors and paramedics assessed people who had sustained major traumatic injuries. People with severe bleeding and a critically low blood pressure were recruited into the trial. The critical care team opened the sealed box and administered the contents of the box (blood/plasma or saline). The trial compared how effective the treatments were by looking at a combined outcome comprising (1) how quickly the body cleared a waste product called lactate and (2) whether the individual died.
Four hundred and thirty-two people participated in the trial, slightly less than the 490 planned due to the trial being interrupted by COVID-19. Two hundred and nine people were in the blood/plasma group and 223 in the 0.9% saline group. The combined outcome of lactate clearance and mortality was very similar between the two groups occurring in around 6 out of 10 people in each group.
Further research is required to work out who might benefit from pre-hospital blood/plasma and how best to measure that benefit in future trials.
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