Fluid resuscitation in trauma: a topic about which there are almost certainly more strong opinions than there are strong studies. We have moved away from crystalloid and towards using blood products, which makes some sense, given that is what the patient is losing. One question that remains is the role of plasma in resuscitating these patients, which leads us to this RCT.
The paper: PAMPer
Sperry JL, Guyette FX, Brown JB, et al. Prehospital Plasma during Air Medical Transport in Trauma Patients at Risk for Hemorrhagic Shock. The New England journal of medicine. 2018; 379(4):315-326. PMID: 30044935
PAMPer is a pragmatic, multicentre, cluster-randomized trial.
Patients: Adult trauma patients (18-90 years old) being transported by an air ambulance service, either directly from the scene of the injury or from an outside hospital, who were at risk of hemorrhagic shock, defined as 1 episode of hypotension (SPB<90) and tachycardia (HR>108) or severe hypotension (SBP<70).
- Exclusions: Unable to establish and IV or IO, isolated fall from standing, known cervical cord injury, prisoners, pregnant females, traumatic cardiac arrest > 5minutes, penetrating brain injury, isolated hanging or drowning, >20% total body surface area burns, admitted to an outside hospital, or refusal to participate by patient or family.
- Randomization was done by air ambulance service, not at the patient level. There were a total of 27 air ambulance services included, all in the United States.
Intervention: 2 units of thawed plasma (group AB or A with a low anti-B antibody titer), given before other resuscitation fluids.
Comparison: Standard crystalloid resuscitation as guided by the air ambulance service protocol (not standardized). 13 of the 27 service also carried 2 units of PRBCs that could be given.
Outcome: The primary outcome was 30 day mortality
501 total patients were enrolled, 390 directly from scene and 111 transferred from an outside hospital.
The primary outcome was 30 day mortality, and was significantly lower in the plasma group: 23.2% vs 33.0%; absolute difference 9.8%, 95% CI 18.8-1.0%; p=0.03
None of the secondary outcomes were statistically significant after adjusting for multiple comparisons, but all the point estimates seem to favour the plasma group.
There were 6 adverse events in 6 patients in the plasma group as compared to 4 in 2 patients in the standard care group. There was 1 transfusion reaction and 2 allergic reactions, including 1 anaphylaxis in the plasma group.
PAMPer is a strong study, with an appropriate primary outcome, looking at an appropriate population, and they also appropriately adjusted for multiple comparisons in their secondary outcomes. But it isn’t a perfect trial. It isn’t blinded. There is a risk for selection bias, as only 523 patients out of 7275 who were screen were included, and we aren’t given details about the reasons for exclusion. Fluid management in the standard care group wasn’t standardized, nor was hospital care post transfer, which might be a problem because the trial wasn’t blinded.
Perhaps my biggest question is: is a 10% decrease in mortality really plausible? That is an unheard of benefit. It’s incredible. It is almost unbelievable, and the skeptic in me wonders whether it will hold up to a repeat trial.
However, PAMPer was an eye opener for me. I won’t be adopting this protocol for all trauma patients yet, but this study has made me reevaluate by stance on balanced transfusion.
Thus far, the vast majority of the evidence for balanced transfusion has come in the form of observational data, where survivorship bias could be playing a large role. The one big RCT, PROPPR, compared a 1:1:1 strategy to a 1:1:2 strategy and showed no difference. (Holcomb 2015) The one other small RCT comparing a 1:1:1 target to standard care had a much higher mortality in the balanced transfusion group, although not statistically so. (Nascimento 2013) Another trial – that I have not had the chance to fully analyze yet – compared using plasma to crystalloid in trauma, and was stopped early for futility. (Moore 2018)
So, although the trauma world has wholeheartedly adopted the concept of balanced transfusion, I remained skeptical. Why would I change my mind? The PAMPer study wasn’t about balanced resuscitation, so strictly speaking, I am probably committing an EBM sin. However, at the core of the balanced transfusion concept is using plasma along side PRBCs. This study provides the first convincing evidence, in my opinion, that plasma might actually help these patients. Truthfully, I am already using some form of balanced transfusion, because every trauma team leader I am transferring to wants their patients treated that way, but this study makes me more comfortable that it might be the best thing for my patients.
That being said, I think we are a long way from knowing definitively that our balanced transfusion strategies are beneficial. Similarly, we need more research before widely adopting the plasma first strategy employed here. Using plasma has harms. In this study there was one transfusion reaction and one case of anaphylaxis. There needs to be a big enough benefit to outweigh the harms. Clearly a 10% mortality benefit would be wonderful, and if this holds up in future studies, it will be the biggest advance in trauma research since the invention of the bandaid.
This unblinded RCT demonstrated a 10% absolute decrease in mortality by using thawed plasma as their primary resuscitation strategy in prehospital trauma patients. This is promising research, but requires replication, preferably in a blinded study.
Holcomb JB, Tilley BC, Baraniuk S, et al. Transfusion of Plasma, Platelets, and Red Blood Cells in a 1:1:1 vs a 1:1:2 Ratio and Mortality in Patients With Severe Trauma JAMA. 2015; 313(5):471-.
Moore HB, Moore EE, Chapman MP, et al. Plasma-first resuscitation to treat haemorrhagic shock during emergency ground transportation in an urban area: a randomised trial The Lancet. 2018; 392(10144):283-291.
Nascimento B, Callum J, Tien H, et al. Effect of a fixed-ratio (1:1:1) transfusion protocol versus laboratory-results-guided transfusion in patients with severe trauma: a randomized feasibility trial Canadian Medical Association Journal. 2013; 185(12):E583-E589.