Fresh Frozen Plasma Should be Given Earlier to Patients Requiring Massive Transfusion

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Abstract
Background: Acidosis, hypothermia, and coagulopathy were identified more than 20 years ago as a deadly triad for patients presenting with exsanguinating hemorrhage. This led to fundamental changes in initial management of severely injured patients. Despite major advances, hemorrhage remains a leading cause of early death in trauma patients. Recent studies report most severely injured patients to be coagulopathic at admission, before resuscitation interventions, and that traditional massive transfusion practice grossly underestimates needs. The hypothesis for this study is that our pre-intensive care unit (ICU) massive transfusion (MT) protocol does not adequately correct coagulopathy, and that early uncorrected coagulopathy is predictive of mortality. Methods: Data maintained in our Trauma Research Database were reviewed. Univariate logistic regression analysis was used to analyze the association of early ICU international normalized ratio (INR) and outcomes, including survival. Results: Ninety-seven of 200 patients admitted during 51 months (ending January 2003) and resuscitated using our standardized ICU shock resuscitation protocol received MT (≥10 units packed red blood cells [PRBC]) during hospital day 1 (age, 39 ± 2; ISS, 29 ± 1; survival, 70%.) All patients required emergency operating room and/or interventional radiology procedures and arrived in the ICU 6.8 ± 0.3 hours after admission. Coagulopathy, present at hospital admission (pre-ICU INR, 1.8 ± 0.2), persisted at ICU admission (initial ICU INR, 1.6 ± 0.1). Pre-ICU resuscitation, 9 ± 1 L crystalloid fluid, 12 ± 1 units PRBC, 5 ± 0.4 units fresh frozen plasma (FFP), was consistent with our MT protocol by which FFP was not given until after 6 units PRBC. ICU resuscitation involved 11 ± 1 L lactated Ringer’s solution (LR) and 10 ± 1 units PRBC. Mean pH was normal within 8 hours. Mean temperature increased from ∼35 °C to >37 °C within 4 hours. In the ICU during resuscitation, patients received 10 ± 1 units FFP for coagulopathy; the ratio of FFP:PRBC was 1:1. Mean INR decreased to 1.4 ± 0.03 within 8 hours and remained nearly constant for the remaining 16 hours of ICU resuscitation, indicating moderate coagulopathy. Statistical analysis found severity of coagulopathy (INR) at ICU admission associated with survival outcome (p = 0.02; area under receiver operator curve [ROC] = 0.71.) Conclusion: These data indicate acidosis and hypothermia to be well managed. Coagulopathy was not corrected in the ICU despite adherence to pre-ICU MT and ICU protocols, likely because of inadequate pre-ICU intervention. More aggressive pre-ICU intervention to correct coagulopathy may be effective in decreasing PRBC requirement during ICU resuscitation, and, because of the association with increased mortality, could improve outcome. We have revised our pre-ICU MT protocol to emphasize early FFP in a FFP:PRBC ratio of 1:1. We think that treatment of coagulopathy can be improved with the development of standardized protocols, both empiric and data driven.