PROPPR

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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 surgeons 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

Metadata

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

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