Giving plasma at a 1:1 ratio with red cells in resuscitation: who might benefit?

I njury is the most common cause of death in North Americans aged 1 to 45 and the most important cause of the loss of productive life for all Americans. Traumatic injury kills 93,000 people in the United States each year with about half dying before they reach the hospital. Profound neurologic injury is the most common cause of death in trauma centers and uncontrolled hemorrhage is the second, but for patients who reach the hospital alive and subsequently die, uncontrolled hemorrhage is the most common cause of potentially preventable death. Thus, about 20,000 people die in the hospital of uncontrolled hemorrhage each year in the United States and the best estimate is that 3000 to 4000 of these deaths, 15 to 20 percent, are potentially preventable. These patients are typically massively transfused and coagulopathic, and control of their coagulopathy appears to be critical in saving them. In response to this epidemic of severe injury, the United States and Canada have built 1082 trauma centers. Nevertheless, the numbers above demonstrate a fundamental difficulty in gathering experience in treating massively hemorrhaging patients. The typical trauma center sees only 20 patients a year who bleed to death, and even in the largest centers, the total number of massively transfused patients, those who receive more than 10 units of red cells (RBCs) in the first 24 hours of care, is less than 100 patients a year. Individual experience, for all but a handful of senior trauma specialists, is limited. Furthermore, there are very few well-designed studies of massive transfusion techniques. A result is that trauma resuscitation guidelines have been based on expert opinion. The current controversy over the increased use of plasma in massive trauma resuscitation illustrates this conundrum. Some trauma centers try to prevent or treat coagulopathy by giving plasma, and others try to prevent transfusion-related acute lung injury (TRALI) or multiple organ failure by using plasma sparingly. Data are now emerging from casualty care in the war in Iraq. The US Army combat support hospital in the Green Zone in Baghdad has cared for more than 8000 casualties, transfused more than 2000 injured, and massively transfused more than 600 young, previously healthy soldiers. In a review of all the US casualties massively transfused at this busiest combat support hospital, Borgman and colleagues have shown that there is an association between the ratio of the numbers of units of plasma to units of RBCs transfused and mortality. Casualties who received less than 1 unit of plasma for every 4 units of RBCs had a 65 percent mortality while those who received more than 2 units of plasma for every 3 units of RBC experienced only 19 percent mortality. These data have been widely presented, and in many US trauma centers the use of a 1:1 ratio of plasma to RBCs is being implemented. Additionally, these data are beginning to affect patterns of blood product administration in situations far removed from trauma surgery. The Army data are retrospective and therefore confounded to some extent by treatment biases imposed by injury severity and resource availability. Soldiers who died after receiving 10 units of RBCs in additive solution but before large amounts of plasma could be thawed, or fresh whole blood collected, are counted in the low-ratio group despite what might have been their “intention-to-treat” status in a randomized prospective study. Nevertheless, the Army data are complete, covering essentially all massively transfused individuals, and provide useful information on a plausible mechanism, a dose-response, and a profound effect. Furthermore, the visibility of these effects From the Departments of Pathology, Trauma Anesthesiology, and Trauma Surgery, University of Maryland School of Medicine, Baltimore, Maryland; and United States Army Institute of Surgical Research, San Antonio, Texas. Address reprint requests to: John R. Hess, MD, MPH, FACP, FAAAS, Blood Bank, N2W50a, University of Maryland Medical Center, 22 South Greene Street, Baltimore, MD 21201; e-mail: [email protected]. This work was supported in part by NHLBI Grant 1U01HL072359-06. The opinions expressed in this work are those of the authors and are not to be construed as those of the U.S. Army or the U.S. Department of Defense. This is a U.S. Government work; there is no copyright. Received for publication January 18, 2008; revision received January 25, 2008, and accepted January 28, 2008. doi: 10.1111/j.1537-2995.2008.01743.x TRANSFUSION 2008;48:1763-1765.