EBQ:PROPPR Trial
Complete Journal Club 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". JAMA. 2015. 313(5):471-482.
PubMed Full text
PubMed Full text
Clinical Question
- Compare 1:1:1 vs 1:1:2 in safety and efficacy in trauma rescus
Conclusion
- No significant differences in mortality at 24 hours or at 30 days between two groups
- More patients in the 1:1:1 group achieved hemostasis and fewer experienced death due to exsanguination by 24 hours (86% vs 78%; p=0.006)
- Exsanguination in first 24 hours decreased in the 1:1:1 group (9.2% vs 14.6%; p=0.03)
- No other safety differences were identified between the two groups
Major Points
- This was a negative trial - the 1:1:1 was as safe as 1:1:2
- They did not meet the 10% mortality advantage which the study was powered to but found 4.2% improvement in the 1:1:1 group at 24hr and 3.7% at 30d
Study Design
- Randomized clinical trial
- Blood product protocol
- 1:1:1 = 6 plt, (1 RBC, 1 FFP) x 6, 6 plt...
- 1:1:2 = (2 RBC, 1 FFP) x 3, 6 plt, (2 RBC, 1 FFP) x 3, 6 plt...
Population
- 680 patients from of 12 participating level I trauma centers in North America
Patient Demographics
No differences were detected between treatment groups in baseline characteristics
Characteristics | 1:1:1 | 1:1:2 |
---|---|---|
Age | 34.5 (25-51) | 34 (24-50) |
Male | 263 (77.8%) | 283 (82.7%) |
Race - White | 210 (62.1%) | 224 (65.5%) |
Race - Black | 94 (27.8%) | 93 (27.2%) |
Race - Other | 35 (10.4%) | 25 (7.3%) |
Inclusion Criteria
- Highest trauma level activation
- ≥15 yo or weight ≥50 kg if age unknown
- Received directly from the injury scene
- Transfusion initiated with at least 1 U of blood component within the first hour of arrival
- Predicted to receive a massive transfusion
Exclusion Criteria
- Received a lifesaving intervention from OSH
- Terminal injuries and expected to die within 1 hour of admission (eg, lethal traumatic brain injury)
- Directly admitted from a correctional facility
- Required a thoracotomy prior to randomization
- <15 yo or <50 kg if age unknown
- Pregnant
- Burns >20% total BSA
- Suspected inhalation injury
- >5 mins of CPR
- DNR
- Enrolled in a concurrent, ongoing, interventional, randomized clinical trial
- >3 U of pRBC given before randomization
Interventions
- Two cohorts received blood product ratios of 1:1:1 (n=338) vs 1:1:2 (n=342) during active resuscitation
Outcomes
Primary Outcome
- Absolute percentage group differences for 24-hour and 30-day mortality
Time Period | 1:1:1 n=338 |
1:1:2 n=342 |
Difference | Adjusted RR | p value |
---|---|---|---|---|---|
24h mortality | 43 (12.7%) | 58 (17.0%) | −4.2 (−9.6-1.1) | 0.75 (0.52-1.08) | 0.12 |
30d mortality | 75 (22.4%) | 89 (26.1%) | −3.7 (−10.2-2.7) | 0.86 (0.65-1.12) | 0.26 |
Secondary Outcomes
- Time to hemostasis
- 1:1:1 - 291 (86.1%)
- 1:1:2 - 267 (78.1%)
- p=0.006
- Exsanguination within first 24h
- 1:1:1 - 9.2%
- 1:1:2 - 14.6%
- p=0.03
- Exsanguination within 30d
- 1:1:1 - 10.7%
- 1:1:2 - 14.7%
- p value no reported
- Number and type of blood products used from randomization until hemostasis was achieved
- 1:1:1 - 25.5 units (pRBC 9u, FFP 7u, Plt 12u)
- 1:1:2 - 19 units (pRBC 9u, FFP 5u, Plt 6u)
- p=0.001 for units of platelets
- Number and type of blood products used after hemostasis was achieved up to 24 hours postadmission
- 1:1:1 group received fewer blood products during the postintervention period than the 1:1:2 group (median of 1 U vs 2 U, respectively)
- Analysis of 23 complications
- Differences were not detected in any of the 23 complications at 30 days
- Incidence of major surgical procedures
- 1:1:1 - 290 (85.8%)
- 1:1:2 - 284 (83.0%)
- Functional status at hospital discharge or 30 days (median , whichever occurred first
- 1:1:1 - 4 (3-6)
- 1:1:2 - 4.5 (3.5-7.0)
- p=0.11
- Hospital-free days, ventilator-free days, and ICU-free days
1:1:1 | 1:1:2 | p value | |
---|---|---|---|
Hospital-free days | 1 (0-17) | 0 (0-16) | 0.83 |
Ventilator-free days | 8 (0-16) | 7 (0-14) | 0.14 |
ICU-free days | 5 (0-11) | 4 (0-10) | 0.10 |
Criticisms & Further Discussion
- This was ultimately an unblinded and was a negative primary outcome due to the powering to detect only an absolute difference of 10% in mortality. To reach statistical significance for a small effect, 2968 patients would have been required to detect the observed difference of 4.2% (24 hour mortality) with 90% power. Regardless this is the best evidence to date the 1:1:1 ratio is a safe and effective treatment. [1]
- The 1:1:1 group received platelets first (six units) followed by alternating RBCs and plasma. However, the 1:1:2 group received two unis RBCs first followed by 1 unt of plasma. Patients were not given until the patient received 9 units of other blood products. This makes interpretation of the results unclear since the platelets not the ratio may have been responsible for the early hemostasis achieved.
- Study design was randomized, multi-centre, and pragmatic, with minimal loss to 30 day followup, and allocation concealed during trial duration.
- Transfusion complications may be more likely related to the increased use of platelets in the treatment arm.
- This trial did not truly compare 1:1:1 vs 1:1:2 resuscitative strategies. Rather Holcomb et al examined a protocol intending to give 1:1:1 vs 1:1:2. In reality, neither group truly reached their proportional expectations. The 1:1:1 group in actuality was given products closer to a 2:1:2 ratio, while the 1:1:2 group only received products in a 2:1:4 ratio. [2]
- Lab guided strategies in smaller sample sizes have not demonstrated 1:1:1 to be superior[3]
External Links
Funding
- US National Heart, Lung, and Blood Institute grant U01HL077863
- Department of Defense
- The Defence Research and Development Canada in partnership with the Canadian Institutes of Health Research-Institute of Circulatory and Respiratory Health (grant CRR-120612)
References
- ↑ Radecki R. The Fixed-Ratio Massive Transfusion Answer. http://www.emlitofnote.com/2015/02/the-fixed-ratio-massive-transfusion.html
- ↑ EM Nerd. The Adventure of the Blanched Soldier. http://emnerd.com/adventure-blanched-soldier/
- ↑ Bartolomeu et al. “Effect of a Fixed-Ratio (1:1:1) Transfusion Protocol Versus Laboratory-Results–guided Transfusion in Patients with Severe Trauma: a Randomized Feasibility Trial.” CMAJ : Canadian Medical Association Journal 185.12 (2013): E583–E589. PMC. Web. 6 Feb. 2015.