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. 

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 12 North American Level 1 trauma centre sites 11185 screened, 680 patients randomised (338 to intervention, 342 to control)

Inclusion criteria 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 criteria 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

Intervention vs Control 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

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

Conclusion 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 A ratio of 1:1:1 resulted in reduced mortality from  exsanguination within the 1st 24 hours