Critical Care | 2019
Pre-hospital plasma transfusion: a valuable coagulation support or an expensive fluid therapy?
Abstract
Two recent clinical trials with conflicting results have refuelled the discussion on pre-hospital plasma in trauma. The multicentre, cluster-randomized PAMPer trial assessed the efficacy and safety of two units of pre-hospital plasma versus standard care without plasma in 501 trauma patients at risk for haemorrhagic shock during air medical transport to a designated US trauma centre [1]. The mortality at 30 days was lower in the plasma compared to the standard care group (23% vs 33%; p = 0.03). The randomized, placebo-controlled COMBAT trial compared the same plasma volume versus isotonic saline in 144 haemorrhagic shocked trauma patients within a US ground EMS and a single US trauma centre but mortality at 28 days did not differ between trial groups (15% vs 10%; n.s.) [2]. Table 1 summarizes the basic characteristics of both trials. The results from both trials need to be viewed with caution against their limitations and may not be translated directly into routine without addressing a number of critical issues. A single drop in blood pressure as an inclusion criterion for both trials is problematic as pre-hospital hypotensive episodes can have non-bleeding reasons (e.g. anaesthesia, cardiac, spinal trauma or wrong readings), and, in PAMPer, half of the patients had received pre-hospital intubation/mechanical ventilation while for COMBAT no details were provided. Both trials aimed for patients “at risk for haemorrhagic shock” or “thought to be due to acute blood loss” but no signs of bleeding were considered for inclusion. Notably, 111 patients in PAMPer had received unspecified pre-treatment prior to inclusion which may have introduced bias. The time span for inclusion expanded over 3 years with trauma care subject to change over time, e.g. the increasing widespread use of antifibrinolytic tranexamic acid (TXA). In COMBAT, 10% of patients had received TXA while its use was not reported for PAMPer. There was high mortality difference at 24-h and 28/ 30-days within both control arms which had assumingly received comparable US standard trauma care after hospital admission (Table 1). With identical entry criteria, this difference may only be explained by differences in injury severity, volume status and further pattern and/or patient care; but no specific details were provided. The comparison of injury severity between both trials is difficult due to different scores applied. However, the mortality in PAMPer was higher than in COMBAT and that reported elsewhere which limits the external validity of findings. In the European RETIC trial on early coagulation factor concentrates versus FFP in trauma the 30-day mortality was only 7.4% despite an ISS of 34 [3]. The German Trauma Registry (TR-DGU) confirms a mortality < 10% for an ISS 20–23 [4]. In PAMPer, there was no clinical benefit for plasma on the sequalae of hypovolaemichaemorrhagic shock as 32% versus 29% of patients died in haemorrhagic shock. The underlying mechanism by which the two units of pre-hospital plasma may have promoted lower mortality in PAMPer remains speculative. In both trials, no relevant improvements in standard/viscoelastic coagulation assays were reported after pre-hospital plasma. A statistically relevant but clinically insignificant shorter prothrombin ratio was reported for the plasma group (1.2 vs 1.3) but cannot account for the observed difference in mortality. In COMBAT, more patients in the plasma group had an INR > 1.3. The INR quantifies only pro-coagulants and does not mirror concentrations of inhibitors. In trauma, INR can be prolonged despite upregulated thrombin generation potential [5]. Moreover, the INR of FFP is 1.3 [6]. Any beneficial effect of plasma to correct slightly elevated INR is futile and plasma has primarily an effect on coagulation parameters with extended volumes and