The prospective, observational, multicenter, major trauma transfusion (PROMMTT) study: comparative effectiveness of a time-varying treatment with competing risks

Abstract

Objective: To relate in-hospital mortality to early transfusion of plasma and/or platelets and to time-varying plasma:red blood cell (RBC) and platelet:RBC ratios.

Design: Prospective cohort study documenting the timing of transfusions during active resuscitation and patient outcomes. Data were analyzed using time-dependent proportional hazards models.

Setting: Ten US level I trauma centers.

Patients: Adult trauma patients surviving for 30 minutes after admission who received a transfusion of at least 1 unit of RBCs within 6 hours of admission (n = 1245, the original study group) and at least 3 total units (of RBCs, plasma, or platelets) within 24 hours (n = 905, the analysis group).

Main outcome measure: In-hospital mortality.

Results: Plasma:RBC and platelet:RBC ratios were not constant during the first 24 hours (P < .001 for both). In a multivariable time-dependent Cox model, increased ratios of plasma:RBCs (adjusted hazard ratio = 0.31; 95% CI, 0.16-0.58) and platelets:RBCs (adjusted hazard ratio = 0.55; 95% CI, 0.31-0.98) were independently associated with decreased 6-hour mortality, when hemorrhagic death predominated. In the first 6 hours, patients with ratios less than 1:2 were 3 to 4 times more likely to die than patients with ratios of 1:1 or higher. After 24 hours, plasma and platelet ratios were unassociated with mortality, when competing risks from nonhemorrhagic causes prevailed.

Conclusions: Higher plasma and platelet ratios early in resuscitation were associated with decreased mortality in patients who received transfusions of at least 3 units of blood products during the first 24 hours after admission. Among survivors at 24 hours, the subsequent risk of death by day 30 was not associated with plasma or platelet ratios.

Conflict of interest statement

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Holcomb reported serving on the board for Tenaxis, the Regional Advisory Council for Trauma, and the National Trauma Institute; providing expert testimony for the Department of Justice; grants funded by the Haemonetics Corporation, and KCI USA, Inc. and consultant fees from the Winkenwerder Company. Dr Wade reported serving on the Science Board for Resuscitation Products, Inc. and the Advisory Board for Astrazeneca. No other disclosures were reported.

Figures

Figure 1. Blood product use in the 1st 6 hours in two PROMMTT patients

Patient A had an ISS of 48 and died of hemorrhage at 1 hour, 7 minutes after ED admission. Patient B had an ISS of 57 and was discharged to another acute care hospital at 27 days. Note the constantly changing ratios over time. For example, patient A received cumulative plasma:platelet:RBC ratios of 0:0:1, 0:0:3, 0:0:6, 4:6:6, and 5:6:6 at 15, 30, 45, 60 and 75 minutes respectively, while patient B received 0:0:1, 0:0:4, 0:0:4, 2:0:6, and 2:0:10 at those same time points.

Figure 2

The bars represent cumulative ratios at the start of each time interval. The majority of patients received 1:2 plasma:RBC ratio or higher by three hours and for platelets:RBC, by six hours. In the last time interval (24 hours), the percentage for patients receiving 0 platelets or plasma increases, reflecting the dynamic cohort with newly eligible patients entering and others exiting due to death in the previous interval.

Figure 2

The bars represent cumulative ratios at the start of each time interval. The majority of patients received 1:2 plasma:RBC ratio or higher by three hours and for platelets:RBC, by six hours. In the last time interval (24 hours), the percentage for patients receiving 0 platelets or plasma increases, reflecting the dynamic cohort with newly eligible patients entering and others exiting due to death in the previous interval.