Invited Commentary to “Performance Improvement Program Review of Institutional Massive Transfusion Protocol Adherence: An Opportunity for Improvement”

In this issue of The American Surgeon, Easterday and colleagues from Memphis retrospectively examined trauma patients who received at least six red blood cells (RBC) units within 4 h of presentation to determine their compliance with balanced blood product guidelines. They were unsuccessful in achieving their goal ratio in 61.4% of massive transfusions, and the inpatient mortality for these patients was 66.5% higher (33.6% vs 20.3%; P = .005). We applaud the authors on their project because performance improvement is one of the most critical factors in improving outcomes. However, we are concerned by their findings and believe they raise some important questions.

Balanced blood product resuscitation and massive transfusion protocols are the most extensively discussed topics in trauma research over the last 15 years. Multiple retrospective studies demonstrated improved survival for patients who received early, balanced blood products.^1,2 As a result, centers across the US changed their protocols and policies for the care of the exsanguinating patients by adopting the principles of Damage Control Resuscitation. These efforts culminated in the PROPPR study, which compared 1:1:1 versus 1:1:2 (platelet:plasma:RBC) resuscitation because balanced resuscitation with these ratios had become the standard of care by the early 2010s. This multicenter randomized controlled study showed no difference in mortality at 24 h or 30 days (the FDA-mandated primary endpoints) but reduced time to hemostasis in the 1:1:1 arm. There was also a decrease in mortality at 3 h (the average time to traumatic death from bleeding) and decreased deaths from hemorrhage at 24 h. ³

Most high-level trauma centers in the United States have adopted a 1:1:1 resuscitation goal with equal units of plasma and platelets to RBCs. The authors of this study work at a trauma center that employs a 1:1:2 approach (two RBCs for every unit of plasma and platelets). Besides increased early mortality in the PROPPR trial, there is no strong evidence this is programmatic. However, that assumes goal ratios are achieved, and achieved early. Easterday’s study is eye-opening because it demonstrates that a well-developed and busy Level 1 trauma center did not achieve its low plasma and platelet goal ratios more than 60% of the time. Snyder and colleagues demonstrated the potential for survival bias from fresh frozen plasma (FFP) thawing time more than a decade ago. ⁴ Since then, multiple methods to decrease the time required to transfuse plasma have been described, including emergency department storage of thawed plasma, liquid (never-frozen) plasma, or whole blood. In each instance, making these balanced blood products available earlier was associated with improved survival.^5,6

The second concerning finding from this study is the dramatic increase in mortality for patients who did not achieve at least a 1:2 ratio of plasma to RBCs. Non-compliance with MTP ratios of plasma and platelets has previously been associated with worse outcomes. ² Assuming survival bias from the time required to thaw FFP is not the cause of this, a two-thirds increase in death for patients who do not achieve appropriate quantities of plasma is very concerning and should cause all trauma centers to work diligently to create systems that allow for the achievement of these ratios without fail. This may include discarding transfusion ratio goals of 1:2 in favor of 1:1 so that even if ratios of 1:1 are not achieved, they do not exceed 1:2. Another option is using whole blood, which provides physiologically developed ratios of all blood components and has proven safe and effective for trauma patients. ⁷

Finally, and perhaps most importantly, the timely delivery of blood products matters. Every study in the last decade examining outcomes from hemorrhage-related interventions has demonstrated that patients bleed to death (or are saved) within two to three hours of injury. Whether advocating for 1:1:1 or 1:1:2, the timeliness of delivering these products is critical. The PROPPR study demonstrated the median time from patient arrival to MTP activation was 9 min, with an additional time from activation to first MTP cooler delivery of 8 min. ⁶ These delays were associated with increased time to hemostasis and worse outcomes. In fact, for every 60-s delay in the arrival of the first MTP cooler to the bedside, mortality increased by 5%. To address this, investigators have evaluated prehospital activation of their MTP, to have coolers ready and waiting for the patient, based on field physiology and ultrasound. ⁸ Other options to reduce time to products and improve compliance are having RBC and thawed or liquid plasma available in the emergency department while waiting on MTP cooler arrival or placing these critical products in ambulances or emergency transport helicopters. Such efforts are supported by a multicenter, randomized trial showing improved survival with prehospital plasma versus standard resuscitation. ⁹

Ratios matter. Compliance matters. Time matters. Regardless of ratio preference, performance improvement processes can help achieve optimal delivery of blood products and hemostatic adjuncts, with improved survival achieved. We applaud the authors' work in evaluating their program’s MTP and identifying areas for further optimization of care delivery.