PROPPR: 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

PROPPR Study Group*, JAMA. 2015;313(5):471-482

Clinical Question

• In patients with severe trauma and predicted to require massive transfusion, does the use of a transfusion protocol using a 1:1:1 ratio of plasma to platelets to red blood cells (RBCs) compared to 1:1:2 improve mortality?

Design

• Randomised-controlled trial
• Treating clinicians non-blinded
• Allocation concealment maintained through use of sealed containers of blood products
• Blinding of assessors of primary outcome
• Sample size calculation
  • Sample size increased from 580 to 680 patients according to “trial’s adaptive design” due to lower actual mortality than predicted
  • With sample size of 680 patients
    • 95% power to detect 10% absolute difference in mortality at 24 hours
    • 92% power to detect 12% absolute difference in mortality at 30 days

Setting

• 12 North American Level 1 trauma center sites
• 3rd August 2012 – 2nd December 2013

Population

• Inclusion:
  • Highest trauma level activation
  • Estimated age 15 years or older or greater than/equal to weight of 50 kg if age unknown
  • Received directly from scene of injury
  • Received at least 1 U of blood product in pre-hospital setting or within 1 hour of arrival to hospital
  • Predicted to receive a massive transfusion by Assessment of Blood Consumption Score ≥ 2 or by the attending trauma surgeon’s judgment
• Exclusion:
  • Received a life saving intervention from another hospital
  • Non-survivable injuries
  • Prisoners directly admitted from jail
  • Required emergency thoracotomy prior to randomisation
  • Obvious pregnancy
  • Severely burned
  • Had at least 5 minutes of CPR with chest compressions before admission
  • Known “Do Not Resuscitate” orders prior to randomization
  • Enrolled in a concurrent ongoing interventional, randomized clinical trial
  • Patients who wear “opt-out” bracelet
  • >3 U RBCs given before randomization
  • PROPPR products not given within 2 hour period
  • Patient improved, did not require further transfusion

• 11185 screened, 680 patients randomised (338 to intervention, 342 to control)
  • Groups eventually matched including Injury Severity Scores and Revised Trauma Scores (median ISS score 26)

Intervention

• Blood product ratios of 1:1:1 (plasma:plts:RBCs)
  • Packs contained 6 U plasma, 1 dose plts (pool of 6 U) and 6 U RBCs

Control

• Blood product ratios of 1:1:2 (plasma:plts:RBCs)
  • Alternating packs containing 3 U plasma, 0 dose plts and 6 U RBCs with 3 U plasma, 1 dose plts and 6 U RBCs

In both intervention and control group

• Blood products administered in a pre-specified order to maintain assigned ratios
• Transfusion stopped when clinically indicated

Outcome

• Primary outcome:
  • 24 hour mortality – no significant difference
  • 30 day mortality – no significant difference

• Secondary outcome:
  • No significant difference in:
    • Time to haemostasis
    • Any of 23 pre-defined complications
    • Hospital-, ventilator, and ICU-free days
    • Incidence of surgical procedures
    • Functional status at discharge
  • Blood product volumes transfused
    • Until haemostasis achieved – no significant difference
    • After haemostasis till 24 hours post-admission – significantly higher in intervention group
  • Post-Hoc Analysis
    • Death by Exsanguination in 1st 24 hours– significantly decreased in intervention group
    • Achieved haemostasis – significantly greater in intervention group

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.

Strengths

• Randomised, multi-centre, pragmatic
• Targeted most severely injured trauma patients predicted to be at highest risk of haemorrhage
• Pre-specified transfusion order to maintain target ratios
• Sample size increased to maintain statistical power
• Minimal loss during follow up
• Allocation concealment contained

Weaknesses

• Unblinded
• 30 day maximum follow up time
• Powered to detect an absolute difference of 10% in mortality – unable to detect smaller effect
  • 2968 patients would have been required to detect the observed difference of 4.2% (24 hour mortality) with 90% power

The Bottom Line

• Among patients with severe trauma and major bleeding there was no significant difference in 24 hour or 30 day mortality in patients who received a blood product transfusion at a ratio of 1:1:1 compared to a ratio of 1:1:2. However the study was significantly underpowered for the observed difference in mortality found.
• A ratio of 1:1:1 resulted in reduced mortality from  exsanguination within the 1st 24 hours, with similar complication rates to a lower ratio protocol. Therefore, I will continue to aim for a 1:1:1 ratio in this population.

External Links

• [Article – abstract & supplementary data] ] 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
• [Podcast – FOAMed] EMCrit Podcast 13 – Trauma Resus II: Massive Transfusion
• [RebelEM – FOAMed] REBELEM PROPPR
• [EMNerd – FOAMed] EM Nerd
• [EM Literature of Note – FOAMed] EMLitofNote
• [MDCalc] Assessment-of-blood-consumption-for-massive-transfusion
• [St Emlyn’s] Getting the Balance Right: The PROPPR Trial
• [SGEM] SGEM #109 One Platelet, One Plasma and One RBC – PROPPR Trial

Metadata

Summary author: @avkwong
Summary date: 7th Feb 2015
Peer-review editor: @davidslessor