Today, we discuss the PROPPR Trial with its lead author, John Holcomb, MD. This was an RCT of trauma patients with severe hemorrhage. It pitted 1:1:1 matched product transfusion with a 1:1:2 control group. Dr. Holcomb is a Trauma Surgeon at University of Texas, Houston. He spent decades in the military as a surgeon before continuing his career in Houston.
This podcast is coming out a week early, but it is too good to wait!
As per their routine, the Bottom Line Review summarized the study beautifully:
Questions I discussed with Dr. Holcomb
- If you had to give the elevator pitch for the take-home message of the trial, what would it be?
- The doubters may say that the control group in the study should have been 1:3 (plasma:rbc) or even no fixed ratio, but solely an INR/Plt lab based approach. They may say that PROPPR shows 1:1:1 is as good as or better than 1:1:2, but may not be better than a much lower rate of plasma and PLT transfusion. What do you say to this line of commentary?
- The trigger for massive transfusion in the PROPPR trial was ABC>=2 or clinician judgment. Do you bother with scores in your personal practice? Should we be using them?
- In the 1:1:1 group, platelets were given up front (0 unit mark). In the 1:1:2 group, they were only given after 9 units of product. What was the rationale for this? Do you think it might have made a difference?
- It seems the 1:1:2 group played catch up for plasma over the next 24 hours. Do you think this supports the contention that early 1:1:1 may spare the need for products down the road, especially in light of the fact that exsanguination deaths were an early phenomenon.
- Median RBCs were 9 units over 24 hours, which means over half of the patients did not receive the 10 units of RBC that traditionally define Massive Transfusion. Should we redefine MT? What is the point at which it was beneficial to have matched plasma/plt to RBCs.
- This trial was not designed to look at this question, but I want to know what you think. In 2015, should we be using the empiric ratios of the PROPPR trial or should we be switching to a visco-elastic (TEG/TEM) based strategy?
- Let’s do some rapid fire… Aside from the randomized intervention, the trial was pragmatic, so I would love to hear your personal feelings and practice on:
- Most studies have a back story—something all of the researchers know, but is not reflected in the word-trimmed, published version. What are we not seeing in the published form of the PROPPR study?
Some key points from the discussion
- Our current definitions of massive transfusion are outdated. Better may be the Critical Administration Threshold–if you give 3 units of blood in any 1 hour period, it is a massive transfusion. But…
- Dr. Holcomb doesn't wait for the 3 unit threshold. At his shop, they try to make the 1st unit transfused plasma or platelets and start matched transfusion from that point forward.
- In the PROPPR trial, only about 2/3 of the patients received TXA, but CRASH2 indications would have had all of them receive it. Dr. Holcomb uses TEG to decide, and wants to see more RCTS (they are being done) to better clarify the role of TXA. For more on that though, see my podcasts with Tim Fabian and Karim Brohi. Vicoelastic tests may be insensitive to fibrinolysis based on these discussions.
- The Kaplan-Meier curves for a 3 hour endpoint showed a statistically significant mortality difference between the two groups, but this was not one of the allowed primary outcomes.
Articles Mentioned in Dr. Holcomb's Discussion
- PROMMTT Trial: Holcomb JB, et al; PROMMTT Study Group. The Prospective, Observational, Multicenter, Major Trauma Transfusion (PROMMTT) study: comparative effectiveness of a time-varying treatment with competing risks. (JAMA Surg. 2013;148(2):127-136)
- How I Do It (Blood. 2014;124(20):3052-3058) – Describes how Dr. Holcomb actually practices in his shop
- ABC Score
What did the two groups receive in the first 24 hours?
What are others saying?
- Rory Spiegel at EM Nerd: The Adventure of the Blanched Soldier
- Ryan Radecki at EM Literature of Note: The Fixed-Ratio Massive Transfusion Answer
- Salim Rezaie at REBEL EM. The PROPPR Randomized Clinical Trial
- St. Emlyn's Journal Club