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

Research output: Contribution to journalArticle

Abstract

IMPORTANCE: Severely injured patients experiencing hemorrhagic shock often require massive transfusion. Earlier transfusion with higher blood product ratios (plasma, platelets, and red blood cells), defined as damage control resuscitation, has been associated with improved outcomes; however, there have been no large multicenter clinical trials. OBJECTIVE: To determine the effectiveness and safety of transfusing patients with severe trauma and major bleeding using plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio. DESIGN, SETTING, AND PARTICIPANTS: Pragmatic, phase 3, multisite, randomized clinical trial of 680 severely injured patients who arrived at 1 of 12 level I trauma centers in North America directly from the scene and were predicted to require massive transfusion between August 2012 and December 2013. INTERVENTIONS: Blood product ratios of 1:1:1 (338 patients) vs 1:1:2 (342 patients) during active resuscitation in addition to all local standard-of-care interventions (uncontrolled). MAIN OUTCOMES AND MEASURES: Primary outcomes were 24-hour and 30-day all-cause mortality. Prespecified ancillary outcomes included time to hemostasis, blood product volumes transfused, complications, incidence of surgical procedures, and functional status. RESULTS: No significant differences were detected in mortality at 24 hours (12.7%in 1:1:1 group vs 17.0%in 1:1:2 group; difference, -4.2%[95% CI, -9.6%to 1.1%]; P = .12) or at 30 days (22.4% vs 26.1%, respectively; difference, -3.7%[95% CI, -10.2%to 2.7%]; P = .26). Exsanguination, which was the predominant cause of death within the first 24 hours, was significantly decreased in the 1:1:1 group (9.2% vs 14.6%in 1:1:2 group; difference, -5.4%[95% CI, -10.4%to -0.5%]; P = .03). More patients in the 1:1:1 group achieved hemostasis than in the 1:1:2 group (86% vs 78%, respectively; P = .006). Despite the 1:1:1 group receiving more plasma (median of 7 U vs 5 U, P < .001) and platelets (12 U vs 6 U, P < .001) and similar amounts of red blood cells (9 U) over the first 24 hours, no differences between the 2 groups were found for the 23 prespecified complications, including acute respiratory distress syndrome, multiple organ failure, venous thromboembolism, sepsis, and transfusion-related complications. CONCLUSIONS AND RELEVANCE: 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. However, more patients in the 1:1:1 group achieved hemostasis and fewer experienced death due to exsanguination by 24 hours. Even though there was an increased use of plasma and platelets transfused in the 1:1:1 group, no other safety differences were identified between the 2 groups.

Original languageEnglish (US)
Pages (from-to)471-482
Number of pages12
JournalJAMA - Journal of the American Medical Association
Volume313
Issue number5
DOIs
StatePublished - Feb 3 2015

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Platelet Transfusion
Randomized Controlled Trials
Erythrocytes
Mortality
Blood Platelets
Wounds and Injuries
Hemostasis
Exsanguination
Resuscitation
Hemorrhage
Multiple Organ Failure
Hemorrhagic Shock
Trauma Centers
Venous Thromboembolism
Adult Respiratory Distress Syndrome
Standard of Care
Patient Safety
North America
Blood Volume
Multicenter Studies

ASJC Scopus subject areas

  • Medicine(all)

Cite this

@article{c03a1a09134b4d2dba81c3dc12d1617c,
title = "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",
abstract = "IMPORTANCE: Severely injured patients experiencing hemorrhagic shock often require massive transfusion. Earlier transfusion with higher blood product ratios (plasma, platelets, and red blood cells), defined as damage control resuscitation, has been associated with improved outcomes; however, there have been no large multicenter clinical trials. OBJECTIVE: To determine the effectiveness and safety of transfusing patients with severe trauma and major bleeding using plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio. DESIGN, SETTING, AND PARTICIPANTS: Pragmatic, phase 3, multisite, randomized clinical trial of 680 severely injured patients who arrived at 1 of 12 level I trauma centers in North America directly from the scene and were predicted to require massive transfusion between August 2012 and December 2013. INTERVENTIONS: Blood product ratios of 1:1:1 (338 patients) vs 1:1:2 (342 patients) during active resuscitation in addition to all local standard-of-care interventions (uncontrolled). MAIN OUTCOMES AND MEASURES: Primary outcomes were 24-hour and 30-day all-cause mortality. Prespecified ancillary outcomes included time to hemostasis, blood product volumes transfused, complications, incidence of surgical procedures, and functional status. RESULTS: No significant differences were detected in mortality at 24 hours (12.7{\%}in 1:1:1 group vs 17.0{\%}in 1:1:2 group; difference, -4.2{\%}[95{\%} CI, -9.6{\%}to 1.1{\%}]; P = .12) or at 30 days (22.4{\%} vs 26.1{\%}, respectively; difference, -3.7{\%}[95{\%} CI, -10.2{\%}to 2.7{\%}]; P = .26). Exsanguination, which was the predominant cause of death within the first 24 hours, was significantly decreased in the 1:1:1 group (9.2{\%} vs 14.6{\%}in 1:1:2 group; difference, -5.4{\%}[95{\%} CI, -10.4{\%}to -0.5{\%}]; P = .03). More patients in the 1:1:1 group achieved hemostasis than in the 1:1:2 group (86{\%} vs 78{\%}, respectively; P = .006). Despite the 1:1:1 group receiving more plasma (median of 7 U vs 5 U, P < .001) and platelets (12 U vs 6 U, P < .001) and similar amounts of red blood cells (9 U) over the first 24 hours, no differences between the 2 groups were found for the 23 prespecified complications, including acute respiratory distress syndrome, multiple organ failure, venous thromboembolism, sepsis, and transfusion-related complications. CONCLUSIONS AND RELEVANCE: 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. However, more patients in the 1:1:1 group achieved hemostasis and fewer experienced death due to exsanguination by 24 hours. Even though there was an increased use of plasma and platelets transfused in the 1:1:1 group, no other safety differences were identified between the 2 groups.",
author = "{PROPPR Study Group} and Holcomb, {John B.} and Tilley, {Barbara C.} and Sarah Baraniuk and Fox, {Erin E.} and Wade, {Charles E.} and Podbielski, {Jeanette M.} and {Del Junco}, {Deborah J.} and Brasel, {Karen J.} and Bulger, {Eileen M.} and Callcut, {Rachael A.} and Cohen, {Mitchell Jay} and Cotton, {Bryan A.} and Fabian, {Timothy C.} and Kenji Inaba and Kerby, {Jeffrey D.} and Peter Muskat and Terence O'Keeffe and Terence OKeeffe and Robinson, {Bryce R.H.} and Scalea, {Thomas M.} and Schreiber, {Martin A.} and Stein, {Deborah M.} and Weinberg, {Jordan A.} and Callum, {Jeannie L.} and Hess, {John R.} and Nena Matijevic and Miller, {Christopher N.} and Pittet, {Jean Francois} and Hoyt, {David B.} and Pearson, {Gail D.} and Brian Leroux and {Van Belle}, Gerald",
year = "2015",
month = "2",
day = "3",
doi = "10.1001/jama.2015.12",
language = "English (US)",
volume = "313",
pages = "471--482",
journal = "JAMA - Journal of the American Medical Association",
issn = "0002-9955",
publisher = "American Medical Association",
number = "5",

}

TY - JOUR

T1 - 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

T2 - The PROPPR randomized clinical trial

AU - PROPPR Study Group

AU - Holcomb, John B.

AU - Tilley, Barbara C.

AU - Baraniuk, Sarah

AU - Fox, Erin E.

AU - Wade, Charles E.

AU - Podbielski, Jeanette M.

AU - Del Junco, Deborah J.

AU - Brasel, Karen J.

AU - Bulger, Eileen M.

AU - Callcut, Rachael A.

AU - Cohen, Mitchell Jay

AU - Cotton, Bryan A.

AU - Fabian, Timothy C.

AU - Inaba, Kenji

AU - Kerby, Jeffrey D.

AU - Muskat, Peter

AU - O'Keeffe, Terence

AU - OKeeffe, Terence

AU - Robinson, Bryce R.H.

AU - Scalea, Thomas M.

AU - Schreiber, Martin A.

AU - Stein, Deborah M.

AU - Weinberg, Jordan A.

AU - Callum, Jeannie L.

AU - Hess, John R.

AU - Matijevic, Nena

AU - Miller, Christopher N.

AU - Pittet, Jean Francois

AU - Hoyt, David B.

AU - Pearson, Gail D.

AU - Leroux, Brian

AU - Van Belle, Gerald

PY - 2015/2/3

Y1 - 2015/2/3

N2 - IMPORTANCE: Severely injured patients experiencing hemorrhagic shock often require massive transfusion. Earlier transfusion with higher blood product ratios (plasma, platelets, and red blood cells), defined as damage control resuscitation, has been associated with improved outcomes; however, there have been no large multicenter clinical trials. OBJECTIVE: To determine the effectiveness and safety of transfusing patients with severe trauma and major bleeding using plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio. DESIGN, SETTING, AND PARTICIPANTS: Pragmatic, phase 3, multisite, randomized clinical trial of 680 severely injured patients who arrived at 1 of 12 level I trauma centers in North America directly from the scene and were predicted to require massive transfusion between August 2012 and December 2013. INTERVENTIONS: Blood product ratios of 1:1:1 (338 patients) vs 1:1:2 (342 patients) during active resuscitation in addition to all local standard-of-care interventions (uncontrolled). MAIN OUTCOMES AND MEASURES: Primary outcomes were 24-hour and 30-day all-cause mortality. Prespecified ancillary outcomes included time to hemostasis, blood product volumes transfused, complications, incidence of surgical procedures, and functional status. RESULTS: No significant differences were detected in mortality at 24 hours (12.7%in 1:1:1 group vs 17.0%in 1:1:2 group; difference, -4.2%[95% CI, -9.6%to 1.1%]; P = .12) or at 30 days (22.4% vs 26.1%, respectively; difference, -3.7%[95% CI, -10.2%to 2.7%]; P = .26). Exsanguination, which was the predominant cause of death within the first 24 hours, was significantly decreased in the 1:1:1 group (9.2% vs 14.6%in 1:1:2 group; difference, -5.4%[95% CI, -10.4%to -0.5%]; P = .03). More patients in the 1:1:1 group achieved hemostasis than in the 1:1:2 group (86% vs 78%, respectively; P = .006). Despite the 1:1:1 group receiving more plasma (median of 7 U vs 5 U, P < .001) and platelets (12 U vs 6 U, P < .001) and similar amounts of red blood cells (9 U) over the first 24 hours, no differences between the 2 groups were found for the 23 prespecified complications, including acute respiratory distress syndrome, multiple organ failure, venous thromboembolism, sepsis, and transfusion-related complications. CONCLUSIONS AND RELEVANCE: 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. However, more patients in the 1:1:1 group achieved hemostasis and fewer experienced death due to exsanguination by 24 hours. Even though there was an increased use of plasma and platelets transfused in the 1:1:1 group, no other safety differences were identified between the 2 groups.

AB - IMPORTANCE: Severely injured patients experiencing hemorrhagic shock often require massive transfusion. Earlier transfusion with higher blood product ratios (plasma, platelets, and red blood cells), defined as damage control resuscitation, has been associated with improved outcomes; however, there have been no large multicenter clinical trials. OBJECTIVE: To determine the effectiveness and safety of transfusing patients with severe trauma and major bleeding using plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio. DESIGN, SETTING, AND PARTICIPANTS: Pragmatic, phase 3, multisite, randomized clinical trial of 680 severely injured patients who arrived at 1 of 12 level I trauma centers in North America directly from the scene and were predicted to require massive transfusion between August 2012 and December 2013. INTERVENTIONS: Blood product ratios of 1:1:1 (338 patients) vs 1:1:2 (342 patients) during active resuscitation in addition to all local standard-of-care interventions (uncontrolled). MAIN OUTCOMES AND MEASURES: Primary outcomes were 24-hour and 30-day all-cause mortality. Prespecified ancillary outcomes included time to hemostasis, blood product volumes transfused, complications, incidence of surgical procedures, and functional status. RESULTS: No significant differences were detected in mortality at 24 hours (12.7%in 1:1:1 group vs 17.0%in 1:1:2 group; difference, -4.2%[95% CI, -9.6%to 1.1%]; P = .12) or at 30 days (22.4% vs 26.1%, respectively; difference, -3.7%[95% CI, -10.2%to 2.7%]; P = .26). Exsanguination, which was the predominant cause of death within the first 24 hours, was significantly decreased in the 1:1:1 group (9.2% vs 14.6%in 1:1:2 group; difference, -5.4%[95% CI, -10.4%to -0.5%]; P = .03). More patients in the 1:1:1 group achieved hemostasis than in the 1:1:2 group (86% vs 78%, respectively; P = .006). Despite the 1:1:1 group receiving more plasma (median of 7 U vs 5 U, P < .001) and platelets (12 U vs 6 U, P < .001) and similar amounts of red blood cells (9 U) over the first 24 hours, no differences between the 2 groups were found for the 23 prespecified complications, including acute respiratory distress syndrome, multiple organ failure, venous thromboembolism, sepsis, and transfusion-related complications. CONCLUSIONS AND RELEVANCE: 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. However, more patients in the 1:1:1 group achieved hemostasis and fewer experienced death due to exsanguination by 24 hours. Even though there was an increased use of plasma and platelets transfused in the 1:1:1 group, no other safety differences were identified between the 2 groups.

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U2 - 10.1001/jama.2015.12

DO - 10.1001/jama.2015.12

M3 - Article

VL - 313

SP - 471

EP - 482

JO - JAMA - Journal of the American Medical Association

JF - JAMA - Journal of the American Medical Association

SN - 0002-9955

IS - 5

ER -