Older Blood Is Associated With Increased Mortality and Adverse Events in Massively Transfused Trauma Patients: Secondary Analysis of the PROPPR Trial

Jones, Allison R.; Patel, Rakesh P.; Marques, Marisa B.; Donnelly, John P.; Griffin, Russell; Pittet, Jean–François; Kerby, Jeffrey D.; Stephens, Shannon W.; DeSantis, Stacia M.; Hess, John R.; Wang, Henry E.; Holcomb, John B.; Wade, Charles E.; Junco, Deborah J. del; Fox, Erin E.; Matijevic, Nena; Podbielski, Jeanette; Beeler, Angela M.; Tilley, Barbara C.; Baraniuk, Sarah; Zhu, Hongjian; Nixon, Joshua P.; Seay, Roann; Appana, Savitri; Yang, Hui; Gonzalez, Michael O.; Baer, Lisa A.; Wang, Yao-Wei W.; Hula, Brittany S.; Espino, Elena; Nguyen, An; Pawelczyk, Nicholas; Arora-Nutall, Kisha D.; Sharma, R.; Cardenas, Jessica C.; Rahbar, Elaheh; Burnett, Tyrone; Clark, David L.; Belle, Gerald van; May, Susanne; Leroux, Brian G.; Hoyt, David B.; Powell, Judy; Sheehan, Kellie; Hubbard, Alan; Arkin, Adam P.; Callum, Jeanne; Cotton, Bryan A.; Vincent, Laura; Welch, Timothy; Poole, Tiffany; Pivalizza, Evan G.; Gumbert, Sam D.; Bai, Yu; McCarthy, James J.; Noland, A.; Hobbs, Rhonda; Bulger, Eileen M.; Klotz, Patricia; Cattin, Lindsay; Warner, Keir J.; Wilson, Angela; Boman, David; White, Nathan J.; Grabinsky, Andreas; Daniel-Johnson, Jennifer A.; Cohen, Mitchell J.; Callcut, Rachael A.; Nelson, Mary F.; Redick, Brittney J.; Conroy, Amanda S.; Steurer, Marc P.; Maxim, Preston C.; Fiebig, Eberhard; Moore, Joanne I.; Mallari, Eireen; Muskat, Peter; Johannigman, Jay A.; Robinson, Bryce R. H.; Branson, Richard D.; Gomaa, Dina; Barczak, Christopher; Bennett, Suzanne; Carey, Patricia M.; Miller, Christopher N.; Hancock, Helen; Rodriguez, Carolina; Inaba, Kenji; Zhu, J.; Wong, Monica; Menchine, Michael; Katzberg, Kelly; Henderson, Sean O.; McKeever, Rodney; Shulman, Ira A.; Nelson, Janice M.; Tuma, Christopher W.; Matsushita, Cheryl Y.; Scalea, Thomas M.; Stein, Deborah M.; Shaffer, Cynthia K.; Wade, Christine; Herrera, Anthony V.; Kallam, Seeta; S, Wade; Galvagno, Samuel M.; Fontaine, Magali J.; Hunt, Janice M.; Cooke, Rhonda; Fabian, Timothy C.; Weinberg, Jordan A.; Croce, Martin A.; Wilson, Suzanne; Panzer-Baggett, Stephanie; Waddle-Smith, Lynda; Flax, Sherri; Brasel, Karen J.; Walsh, Pamela; Milia, David; Nelson, A Christie; Kaslow, Olga; Aufderheide, Tom P.; Gottschall, Jerome L.; Carpenter, Erica L.; OʼKeeffe, Terence; Rokowski, Laurel L.; Denninghoff, Kurt R.; Redford, Daniel T.; Novak, Deborah J.; Knoll, Susan; Bosarge, Patrick L.; Pierce, Albert; Williams, Carolyn; Schreiber, Martin A.; Watters, Jennifer M.; Underwood, Samantha J.; Groat, Tahnee; Newgard, Craig D.; Merkel, Matthias; Scanlan, Richard M.; Miller, Beth; Rizoli, Sandro; Tien, Homer; Nascimento, Barto; Trpcic, Sandy; Sobrian-Couroux, Skeeta; Reis, Marciano D.; Pérez, Adic; Belo, Susan; Merkley, Lisa L.; Colavecchia, Connie

doi:10.1016/j.annemergmed.2018.09.033

Cited by 40 publications

(40 citation statements)

References 27 publications

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“…For example, trauma patients may constitute a population uniquely vulnerable to the effects of storage duration. Previous reports from Weinberg and colleagues [14][15][16]42 and recently reported mortality results from the PROPPR (Pragmatic, Randomized Optimal Platelet and Plasma Ratios) randomized clinical trial in trauma patients 43 indicate worse outcomes following transfusion with older RBCs, perhaps especially when larger volumes are used. Unfortunately, our study included too few trauma patients (five with hip or lower extremity fractures) to separately analyze their MPAP response to transfusions.…”

Section: Discussionmentioning

confidence: 98%

Blood transfusions, blood storage, and correlation with elevated pulmonary arterial pressures

et al. 2019

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BACKGROUND The aim of this study was to determine if transfusion with RBCs is associated with a rise in mean pulmonary artery pressure (MPAP) and whether such a rise is influenced by the duration of RBC storage. STUDY DESIGN AND METHODS A retrospective chart review of intensive care unit patients with pulmonary artery catheters was conducted at two military medical centers. RESULTS RBC transfusion is associated with a sustained (≥4 hours) statistically significant 2‐ to 3‐mm Hg rise in MPAP relative to both pretransfusion levels (p < 0.05) and compared to asanguinous fluid infusions (p < 0.05). The magnitude of the rise (all infusions, RBCs, and asanguinous) correlates positively with in‐hospital mortality (p < 0.01) and hospital length of stay (p < 0.01). The duration of RBC storage was not statistically correlated with the magnitude of rise in the population studied. Mean infusion volume was greater for RBC (vs. asanguinous) infusions, but volume adjustment of MPAP values did not alter the pattern or statistical significance of the results. CONCLUSIONS Analysis of retrospectively collected data suggests that transfusion of RBC‐containing fluids results in a sustained elevation of MPAP. In the patient population studied, the duration of RBC storage did not correlate with the magnitude of MPAP rise. Future prospective studies of transfusion effects should consider including assessment of MPAP and subpopulation analyses.

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Section: Discussionmentioning

confidence: 98%

Blood transfusions, blood storage, and correlation with elevated pulmonary arterial pressures

et al. 2019

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“…The results of this analysis suggest that the effect of storage age is nonlinear and complex. A volume‐dependent effect of stored RBCs has recently been reported in a secondary analysis of the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial, with an increased risk of death observed only after a threshold of 10 RBC units were transfused 32 . While the association of RBC storage age with mortality observed in this analysis contrasts with the findings of recent randomized, controlled studies, 20–24 the dose effect of storage age was not evaluated in detail in these studies, and these studies may have been underpowered to detect an effect in heavily transfused patients.…”

Section: Discussionmentioning

confidence: 93%

Volume‐dependent effect of stored red blood cells: A secondary analysis of the Age of Blood Evaluation trial

et al. 2020

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Background An increased risk of complications, including death, has been associated with stored red blood cell (RBC) units in observational studies but not in randomized trials. We aimed to evaluate for volume‐dependent effects attributable to length of RBC storage in a secondary analysis of the Age of Blood Evaluation (ABLE) trial. Study Design and Methods In the 2510 critically ill adults from the ABLE trial randomized to receive RBC units stored not more than 7 days or the oldest compatible RBC units, we estimated the hazard ratio (HR) for death by intensive care unit (ICU) and hospital discharge and by days 28, 90, and 180, within subgroups defined by the number of RBC units received. Extended Cox proportional hazards regression was used to model the HR. Results A volume‐dependent effect of storage age on survival was present for death by 90 and 180 days, but not earlier endpoints. The HR for death by 90 days was 0.55 (95% confidence interval [CI], 0.11–0.98, fresh vs standard) after transfusion of 6 RBC units but 1.45 (95% CI, 1.06–1.98) after transfusion of 1 RBC unit. Conclusion In this exploratory analysis, volume‐dependent effects related to RBC storage were documented in the ABLE trial. The harms associated with small volumes of fresh RBC units and large volumes of older RBC units should be further explored.

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“…Notably, none of these trials utilized any direct measure of RBC unit quality. However, a recent trauma study analyzing data from the Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial reported an increased likelihood of 24-hour mortality in patients receiving massive transfusions (> 10 units) of RBCs if older than 22 days (27). In addition, a second study analyzing PROPPR data used a scalar metric (Scalar Age of Blood Index, SBI) that accounted for the distribution of the blood ages of all transfusions received by each patient and found that a higher, more positive SBI (indicating older RBC units were used) was associated with both 24-hour and 30 day mortality, despite adjustments for total units received and clinical covariates (28).…”

Section: Discussionmentioning

confidence: 99%

Using Redox Potential as a Feasible Marker for Banked Blood Quality and the State of Oxidative Stress in Stored Red Blood Cells

Daniels

Jun

Davenport

et al. 2020

Preprint

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Background Stored Red Blood Cells (RBCs) may undergo oxidative stress over time, with functional changes affecting critical tasks such as oxygen delivery. Central to these changes are oxidation-reduction (redox) reactions and the redox potential (RP) that must be maintained for proper cell function. RP imbalance can lead to oxidative stress that may contribute to storage lesions and transfusion-related morbidities. Direct measures of RP may allow for evaluation of erythrocyte quality and enable corrections of RP prior to transfusion. Methods Multiple random RBC segments were tested, ranging in age from 5 to 40 days at 5 day intervals. RP was recorded by measuring open circuit potential of RBCs using novel nanoporous gold electrodes with Ag/AgCl reference. RP measures were also performed on peripheral venous blood samples from 10 healthy volunteers. RP measures were compared between groups of aged RBCs, and with volunteer blood. Results Stored RBCs show time-dependent increases in RP. There were significant differences in Day 5 RP compared to all other groups (p≤0.005), Day 10-15 vs ages ≥ Day 20 (p≤0.025), Day 20-25 vs Day 40 (p=0.039), and all groups compared to healthy volunteers. RP became more positive over time suggesting ongoing oxidation as RBCs age. However, storage time alone does not predict the ultimate RP value measured from a given unit.Conclusions There are significant differences in RP between freshly stored RBCs and all others, with RP becoming more positive over time. However, storage time alone does not predict RP, indicating RP screening may be important independent of storage time and may serve as a marker of RBC quality and state of oxidative stress. RP measurements may also provide a target by which to restore RP balance in aged pRBCs, improving their clinical effectiveness while reducing associated morbidities.

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Older Blood Is Associated With Increased Mortality and Adverse Events in Massively Transfused Trauma Patients: Secondary Analysis of the PROPPR Trial

Cited by 40 publications

References 27 publications

Blood transfusions, blood storage, and correlation with elevated pulmonary arterial pressures

Blood transfusions, blood storage, and correlation with elevated pulmonary arterial pressures

Volume‐dependent effect of stored red blood cells: A secondary analysis of the Age of Blood Evaluation trial

Using Redox Potential as a Feasible Marker for Banked Blood Quality and the State of Oxidative Stress in Stored Red Blood Cells

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