Improved Survival After Hemostatic Resuscitation: Does the Emperor Have No Clothes?

Department of Surgery, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.
The Journal of trauma (Impact Factor: 2.96). 01/2011; 70(1):97-102. DOI: 10.1097/TA.0b013e3182051691
Source: PubMed


In light of recent data, controversy surrounds the apparent 30-day survival benefit of patients achieving a fresh frozen plasma (FFP) to packed red blood cell (PRBC) ratio of at least 1:2 in the face of massive transfusions (MT) (≥10 units of PRBC within 24 hours of admission). We hypothesized that initial studies suffer from survival bias because they do not consider early deaths secondary to uncontrolled exsanguinating hemorrhage. To help resolve this controversy, we evaluated the temporal relationship between blood product administration and mortality in civilian trauma patients receiving MT.
Patients requiring MT over a 22-month period were identified from the resuscitation registry of a Level I trauma center. Shock severity at admission and timing of shock-trauma admission, blood product administration, and death were determined. Patients were divided into high- and low-ratio groups (≥1:2 and<1:2 FFP:PRBC, respectively) and compared. Kaplan-Meier analysis and log-rank test was used to examine 24-hour survival.
One hundred three patients (63% blunt) were identified (66 high-ratio and 37 low-ratio). Those patients who achieved a high-ratio in 24 hours had improved survival. However, severity of shock was less in the high-group (base excess: -8.0 vs. -11.2, p=0.028; lactate: 6.3 vs. 8.4, p=0.03). Seventy-five patients received MT within 6 hours. Of these, 29 received a high-ratio in 6 hours. Again, severity of shock was less in the high-ratio group (base excess: -7.6 vs. -12.7, p=0.008; lactate: 6.7 vs. 9.4, p=0.02). For these patients, 6-hour mortality was less in the high-group (10% vs. 48%, p<0.002). After accounting for early deaths, groups were similar from 6 hours to 24 hours.
Improved survival was observed in patients receiving a higher plasma ratio over the first 24 hours. However, temporal analysis of mortality using shorter time periods revealed those who achieve early high-ratio are in less shock and less likely to die early from uncontrolled hemorrhage compared with those who never achieve a high-ratio. Thus, the proposed survival advantage of a high-ratio may be because of selection of those not likely to die in the first place; that is, patients die with a low-ratio not because of a low-ratio.

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    • "They reported of a possible survivorship bias related to those patients who lived long enough were the ones who received a higher FFP: RBC ratio, suggesting that the difference in mortality was related to factors other than the transfusion therapy. This is in agreement with other recently published studies.[2425] Scalea et al, retrospectively assessed the relationship between FFP transfusion and survival in trauma patients and reported that in a subset of 81 patients who received more than 10 units of RBCs within 24 hours of admission, no significant difference was found between those who received an FFP: RBC ratio of 1 : 1 compared with those who received a lower FFP : RBC ratio when controlling for age, gender ISS, closed head injury, laparotomy status, and length of Intensive care unit (ICU) stay.[24] "
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    ABSTRACT: Continued hemorrhage remains a major contributor of mortality in massively transfused patients and controversy regarding the optimal management exists although recently, the concept of hemostatic resuscitation, i.e., providing large amount of blood products to critically injured patients in an immediate and sustained manner as part of an early massive transfusion protocol has been introduced. The aim of the present review was to investigate the potential effect on survival of proactive administration of plasma and/or platelets (PLT) in trauma patients with massive bleeding. English databases were searched for reports of trauma patients receiving massive transfusion (10 or more red blood cell (RBC) within 24 hours or less from admission) that tested the effects of administration of plasma and/or PLT in relation to RBC concentrates on survival from January 2005 to November 2010. Comparison between highest vs lowest blood product ratios and 30-day mortality was performed. Sixteen studies encompassing 3,663 patients receiving high vs low ratios were included. This meta-analysis of the pooled results revealed a substantial statistical heterogeneity (I(2) = 58%) and that the highest ratio of plasma and/or PLT or to RBC was associated with a significantly decreased mortality (OR: 0.49; 95% confidence interval: 0.43-0.57; P<0.0001) when compared with lowest ratio. Meta-analysis of 16 retrospective studies concerning massively transfused trauma patients confirms a significantly lower mortality in patients treated with the highest fresh frozen plasma (FFP) and/or PLT ratio when compared with the lowest FFP and/or PLT ratio. However, optimal ranges of FFP: RBC and PLT : RBC should be established in randomized controlled trials.
    No preview · Article · Apr 2012 · Journal of Emergencies Trauma and Shock
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    • "Each study of formula-driven resuscitation reviewed by the panel was found to be susceptible to survivorship bias [10]. Two reports that attempted to correct for survivorship bias by treating the blood component ratio as a time-dependent covariate [11,12] found no benefit on mortality. The relationship between blood ratios and survival rates is not linear [13,14], although reported comparisons may have assumed linearity. "
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    ABSTRACT: In June 2011 the Canadian National Advisory Committee on Blood and Blood Products sponsored an international consensus conference on transfusion and trauma. A panel of 10 experts and two external advisors reviewed the current medical literature and information presented at the conference by invited international speakers and attendees. The Consensus Panel addressed six specific questions on the topic of blood transfusion in trauma. The questions focused on: ratio-based blood resuscitation in trauma patients; the impact of survivorship bias in current research conclusions; the value of nonplasma coagulation products; the role of protocols for delivery of urgent transfusion; the merits of traditional laboratory monitoring compared with measures of clot viscoelasticity; and opportunities for future research. Key findings include a lack of evidence to support the use of 1:1:1 blood component ratios as the standard of care, the importance of early use of tranexamic acid, the expected value of an organized response plan, and the recommendation for an integrated approach that includes antifibrinolytics, rapid release of red blood cells, and a foundation ratio of blood components adjusted by results from either traditional coagulation tests or clot viscoelasticity or both. The present report is intended to provide guidance to practitioners, hospitals, and policy-makers.
    Preview · Article · Dec 2011 · Critical care (London, England)
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    ABSTRACT: Current recommendations for resuscitation of the critically injured patient are limited by a lack of point-of-care (POC) assessment of coagulation status. Accordingly, the potential exists for indiscriminant blood component administration. Furthermore, although thromboembolic events have been described shortly after injury, the time sequence of post-injury coagulation changes is unknown. Our current understanding of hemostasis has shifted from a classic view, in which coagulation was considered a chain of catalytic enzyme reactions, to the cell-based model (CBM), representing the interplay between the cellular and plasma components of clot formation. Thromboelastography (TEG), a time-sensitive dynamic assay of the viscoelastic properties of blood, closely parallels the CBM, permitting timely, goal-directed restoration of hemostasis via POC monitoring of coagulation status. TEG-based therapy allows for goal-directed blood product administration in trauma, with potential avoidance of the complications resulting from overzealous component administration, as well as the ability to monitor post-injury coagulation status and thromboprophylaxis. This overview addresses coagulation status and thromboprophylaxis management in the trauma patient and the emerging role of POC TEG.
    Full-text · Article · Oct 2010 · Seminars in Thrombosis and Hemostasis
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