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ACEP Now: Vol 34 – No 04 – April 2015

ACEP Now features one article each issue related to an ACEP eCME CME activity.

Log on to the ACEP eCME CME site to complete the activity for this article and earn free AMA PRA Category 1 Credit.

Case

A 23-year-old male presents to the ED with multiple gunshot wounds to the chest and is hemodynamically unstable. Your clinical gestalt tells you he is going to need a massive transfusion.

Question

What is the effectiveness and safety of transfusing adult patients with severe trauma and major bleeding using plasma, platelets, and red blood cells (RBCs) in a 1:1:1 ratio versus a 1:1:2 ratio?

Background

Trauma is the leading cause of death in the United States among patients between the ages of 1 and 44. The U.S. Department of Defense developed damage-control resuscitation to try to prevent some of these deaths. It involves taking a balanced approach of providing blood products in a 1:1:1 ratio of plasma, platelets, and RBCs.

There have been no large, multicenter, randomized clinical trials with survival as a primary end point. The Prospective, Observational, Multicenter, Major Trauma Transfusion (PROMMTT) was a large observational trial that demonstrated that many clinicians were transfusing patients with a ratio of 1:1:1 or 1:1:2 and that early transfusion of plasma and platelets was associated with improved six-hour survival after admission.

Relevant Article

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: the PROPPR randomized clinical trial. JAMA. 2015;313(5):471-482.

• Population: Patients ≥15 years of age requiring at least 1 U of any blood component within the first hour of arrival or during prehospital transport and/or predicted by the Assessment of Blood Consumption (ABC) Score ≥2 or clinical gestalt to need massive transfusion.
• Intervention: 1:1:1 ratio
• Comparison: 1:1:2 ratio
• Outcome: All cause mortality at 24 hours and 30 days. Secondary outcomes: time to hemostasis, blood product volumes transfused, and complications.

Authors’ Conclusions

“Among patients with severe trauma and major bleeding, early administration of plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio did not result in significant differences in mortality at 24 hours or at 30 days. However, more patients in the 1:1:1 group achieved hemostasis, and fewer experienced death due to exsanguination by 24 hours. Even though there was an increased use of plasma and platelets transfused in the 1:1:1 group, no other safety differences were identified between the two groups.”

Key Results

No statistically significant difference in mortality at 24 hours (12.7 percent versus 17.0 percent) or at 30 days (22.4 percent versus 26.1 percent) for 1:1:1 compared to 1:1:2 ratio.

Exsanguination in first 24 hours significantly decreased (9.2 percent versus 14.6 percent), and more patients achieved hemostasis (86 percent versus 78 percent). More plasma (median 7 U versus 5 U) and platelets (median 12 U versus 6 U) were used in the 1:1:1 ratio versus 1:1:2 ratio, respectively.

There was no difference in complications between the two transfusion strategies.

EBM Commentary

The primary outcome of all-cause mortality was not statistically significant. This does not mean there is no difference between the two protocols, just that there was not a difference greater than 10 percent.

The study was unblinded once the transfusion protocol was started. This could have interfered with the treatment of the patients once they were assigned to one of the two protocols.

The hypothesis to compare 1:1:1 ratio to a 1:1:2 ratio was generated from the PROMMTT study. This was a prospective observational trial, and there could have been confounding factors responsible for the observed mortality benefit.

Another issue is the 1:1:1 group received platelets first (six units) followed by alternating RBCs and plasma. In contrast, the 1:1:2 group received two units of RBCs first followed by one unit of plasma. Platelets were not provided until after receiving nine units of other blood products. It is possible the platelets given first in the 1:1:1 group were responsible for the earlier hemostasis and fewer deaths due to exsanguination by 24 hours.

Bottom Line

A 1:1:1 ratio is a reasonable approach to adult patients who require a massive transfusion and seems to achieve more hemostasis and less death from exsanguination at 24 hours without increased complications.

Case Resolution

The patient was started on a 1:1:1 massive transfusion protocol and had a thoracotomy performed but ultimately did not survive.

Complete the CME activity.

Thank you to Salim Rezaie, MD, FACEP, who is a faculty member at the University of Texas, for his help with this review.

Remember to be skeptical of anything you learn, even if you learned it on The Skeptics’ Guide to Emergency Medicine.

Dr. Milne is chief of emergency medicine and chief of staff at South Huron Hospital, Ontario, Canada. He is on the Best Evidence in Emergency Medicine faculty and is creator of the knowledge translation project the Skeptics’ Guide to Emergency Medicine.

Additional Resources

1. REBEL EM. The PROPPR randomized clinical trial. Available at: http://rebelem.com/proppr-randomized-clinical-trial/. Accessed March 13, 2015.
2. Holcomb JB, del Junco DJ, Fox EE, et al. 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.
3. Tisherman SA, Schmicker RH, Brasel KJ, et al. Detailed description of all deaths in both the shock and traumatic brain injury hypertonic saline trials of the resuscitation outcomes consortium. Ann Surg. 2015;261(3):586-590.
4. Holcomb JB, Jenkins D, Rhee P, et al. Damage control resuscitation: directly addressing the early coagulopathy of trauma. J Trauma. 2007;62(2):307-310.
5. US Army Institute of Surgical Research. Joint theater trauma system clinical practice guideline: damage control resuscitation at level IIb and III treatment facilities. Available at: http://usaisr.amedd.army.mil/cpgs/Damage%20Control%20Resuscitation%20-%201%20Feb%202013.pdf. Accessed March 13, 2015.