Exsanguination is still the major cause of preventable mortality in trauma (6). Haemorrhage control and haemostatic resuscitation are the cornerstones of in-hospital treatment, with delays in transfusion related to increased mortality (7).
The concept of forward resuscitation has brought blood transfusion to the frontline of armed conflicts (8) and there is little doubt amongst the military community that PHBT has helped to decrease battlefield mortality dramatically over the last 20 years (2).
However, scientific evidence to support PHBT as a standard of care in exsanguinating trauma is weak as the majority of all studies on the topic are either underpowered or retrospective. This has hampered its introduction into civilian practice (4, 9). Recently two prospective randomized controlled trials have been published providing some evidence regarding the effect of prehospital plasma in trauma patients. Defrosted plasma compared to standard resuscitation is associated with a survival benefit (NNT of 10) for patients undergoing long transports (median transportation time > 40 minutes) to the receiving hospital (PAMPer) (10); conversely, in an urban environment, no such benefit could be found (COMBAT) (11). This may be related to the significantly shorter transportation times in the second study (median transportation time < 20 min) (5). Of note is that in both studies the mean injury scores (PAMPer: ISS = 22, Combat: NISS = 27) were not particularly high, which could be due to low inclusion thresholds or a prevalence of single organ system injury patterns.
A critical appraisal of both studies (12) comes to the conclusion that the administration of plasma to patients undergoing short transportation times is not justified, and that there still is not enough evidence to give firm recommendations on the use of prehospital fresh plasma.
A post hoc analysis of the PAMPer Trial data (13) found a greater survival benefit for patients resuscitated with PRBC and plasma (HR 0.36), instead of plasma (HR 0.68) or PRBC (0.69) compared to crystalloids. However, the PAMPer Trial was not designed to answer this particular question and therefore the results must be read with caution.
Our survey has found a considerable variation in PHBT practice in Europe with the two largest countries France and Germany employing very different approaches. The return rates in both countries were particularly high (85%). In France, 70% of the prehospital services have access to blood products, whereas in Germany PHBT is hardly ever used. In the light of similar trauma rates and comparable patterns of injury in both countries (14), this is a truly surprising finding and we can only speculate on the underlying reasons. One explanation could be that the French SAMU system is mostly hospital-based with the teams departing from emergency departments having easier access to blood products, than the German advanced prehospital care systems that have become detached from hospital services over the last decades. In some services, PHBP need to be picked-up at the emergency departments on request, but they are not accessible to every trauma patient treated on scene. We must also mention, that the French respondents expressed their opinions from perspective of the ground ambulance providers, while in the other countries’ opinions were represented by the HEMS leads treating patients in haemorrhagic shock more frequently. There are also different (Fig. 5) attitudes towards the use of PHBP, which in part could be explained by the absence of robust scientific evidence for or against PHBT, leaving space for opinion-based approaches. These may be driven by individual views and experience, differences in national regulations, and variable regional availability of blood products.
Haemostatic resuscitation in-hospital relies on the use PRBC and plasma. Early administration of plasma aims at maintaining coagulation (15) and mitigating the inflammatory response to trauma as well as the breakdown of the endothelial glycocalyx (16). Indeed, in-hospital patients with exsanguinating haemorrhage would now never be resuscitated with crystalloid based regimes. This is despite there being no RCT that demonstrates its superiority. There are, however, multiple retrospective studies that together have demonstrated its benefits (1). Currently there are no national or international registries collecting data on PHBP administration making it hard to gain adequate numbers to perform an appropriately powered database analysis.
Risk of wastage of blood products and lack of evidence were given as the main reasons for not using PHBP. Despite this, none of the services using PHBP in our study have reported any wastage. The reported wastage from several other studies is below 2% (3, 17). Even defrosted plasma, with a short shelf-life of six days, can be used in the prehospital environment without wastage. Modern blood boxes can maintain temperatures below six degree Celsius for more than 48 hours. This allows for 24 h rotation cycles for blood products between the HEMS base and the corresponding blood transfusion service. In our own services (Greifswald University Medical Center, Germany and Hradec Kralove HEMS, Czech Republic), we have been applying a rotational system for 9/19 months respectively without any wastage. We suppose, that well-established logistics and cooperation between the HEMS and blood transfusion services might overcome this barrier.
It is surprising that 25% of the services do not operate a blood transfusion policy given that it is mandated within EU guidelines (19) for in-hospital use. Equally only 38% of the services audit their transfusion practice. In our view, the management and the governance of a pre-hospital transfusion program must be under the auspices of the regional blood transfusion service to ensure patient safety, traceability of blood products and compliance with the complex regulations around transfusion. This includes a written transfusion policy and a continuous audit.
Blood transfusion bears the risks of transfusion reactions, infections, hypocalcaemia and hypothermia. The unrestrained or prophylactic use of blood products is not justified. A pre-hospital transfusion policy must include clear indications for the use of PHBT and well-defined transfusion triggers to ensure patient safety and a rational use of this precious resource (19). For the prehospital theatre, it is more difficult to completely define triggers, and other “dynamic” parameters should be considered: rate of bleeding, control of the bleeding, time / distance to the nearest hospital where transfusion could be available, and eventually time for extrication.
Transfusion reactions are not reported in the current study, but a recent systematic review indicates that the incidence of adverse reactions in PHBT is around 1%. (20). This is not surprising because major transfusion reactions (ABO incompatibility) are very unlikely, as blood group 0 is used for red cell transfusion in major haemorrhagic patients without previous blood group determination. Additionally, the immunological response may be diminished in major trauma due to a temporary suppression of the immune system (21). It is also likely that minor transfusion reactions go unnoticed in the setting of major trauma resuscitation and massive haemorrhage. The largest prospective study on PHBP, the PAMPer Trial, reported an incidence of 2.2% of minor transfusion related adverse events but no major incidents after transfusion of defrosted FFP. Another recent systematic literature review concludes that the PHBT is safe and that only minor transfusion reactions have been reported so far (3). The majority of services in our survey do not employ active warming prior to transfusion, which we feel, increases the risk of hypothermia and consequently coagulopathy in major trauma patients.
PHBT is widely used in Europe; and almost 50% of the advanced pre-hospital services (that have responded to our survey) have access to PHBP in the field. Next to PRBC, one third of the services have access to liquid fresh plasma or lyophilized plasma concentrate.
At last, sixty-seven percent of the services have expressed their interest in participating on further research into the topic.
Limitations
- The survey addressed the service leads only and does not consider the views of the complete teams
- The return rates were variable amongst countries. The answers were obtained from 9 of 10 (90%) HEMS bases in the Czech Republic, 52 of 83 (63%) HEMS bases in Germany, and 7 of 12 (58%) HEMS bases in Norway. Therefore, results do not represent the prevailing situation in each country but rather individual opinions of prehospital care providers from certain regions.
- Ten of the services that have replied indicated that they were about to start PHBT programmes. It not unlikely that the number of services that currently use PHBT has increased since the data collection, and some services may have introduced new blood products which were not available in the past, e.g. deleucotized whole blood.
- The French SAMU EMS included in the analysis is known to have different organisation compared to the HEMS systems in other countries. Except France, there were no ground ambulance services or their medical directors requested to provide information on use of PHBP in ground services, unless HEMS base was also responsible for operation of physician response vehicles.
- Finally, we must mention that opinions collected were highly subjective, and may have been affected by clinical experience of each respondent, diversity between systems, and incidence of treated patients requiring early transfusion.