Whole blood versus balanced resuscitation in massive hemorrhage: six of one or half dozen of the other?

INTRODUCTION: Whole blood (WB) resuscitation is increasingly used at trauma centers. Prior studies investigating outcomes in WB versus component-only (CO) resuscitation have been limited by small cohorts, low volumes of WB resuscitation, and unbalanced CO resuscitation. This study aimed to address these limitations using data from a high-volume Level I trauma center, which adopted a WB-first resuscitation paradigm in 2018. We hypothesized that the resuscitation method, WB or balanced CO, would have no impact on patient mortality. METHODS: A single-center, retrospective cohort study of adults presenting as a trauma activation from July 2016 through July 2021 was performed. Receipt of 3 or more units of WB or packed red blood cells (RBC) within the first hour of resuscitation was required for inclusion. Patients were grouped into WB versus CO resuscitation and important clinical outcomes were compared. Mortality was evaluated with Kaplan-Meier analysis, log-rank testing, and multivariable Cox proportional hazards modeling. RESULTS: There were 180 patients in the WB group and 170 patients in the CO group. Of the 180 WB patients, 110 (61%) received only WB during the first 24 hours. The WB group received a median of 5.0 units (IQR 4.0-8.0) of WB and CO group received a median of 6.0 units (IQR 4.0-11.8) of RBCs during the first 24 hours of resuscitation. In the CO group, median RBC/plasma and RBC/platelet ratios approximated 1:1:1. Groups were similar in clinicopathologic characteristics including age, injury severity score, mechanism of injury, and requirement for hemorrhage control interventions (WB 55% vs CO 59%, p = 0.60). Unadjusted survival was equivalent at 24 hours (p = 0.52) and 30 days (p = 0.70) between both groups on Kaplan-Meier analysis with log-rank testing. On multivariable Cox regression, WB resuscitation was not independently associated with improved survival after accounting for age, ISS, mechanism of injury, and receipt of hemorrhage control procedure (HR 0.85, 95% CI 0.61-1.19, p = 0.34). CONCLUSIONS: Balanced CO resuscitation is associated with similar mortality outcomes to that of WB based resuscitation. LEVEL OF EVIDENCE: Level IV; Therapeutic/Care Management.

Abiotic photophosphorylation model based on abiogenic flavin and pteridine pigments.

A model for abiotic photophosphorylation of adenosine diphosphate by orthophosphate with the formation of adenosine triphosphate was studied. The model was based on the photochemical activity of the abiogenic conjugates of pigments with the polymeric material formed after thermolysis of amino acid mixtures. The pigments formed showed different fluorescence parameters depending on the composition of the mixture of amino acid precursors. Thermolysis of the mixture of glutamic acid, glycine, and lysine (8:3:1) resulted in a predominant formation of a pigment fraction which had the fluorescence maximum at 525 nm and the excitation band maxima at 260, 375, and 450 nm and was identified as flavin. When glycine in the initial mixture was replaced with alanine, a product formed whose fluorescence parameters were typical to pteridines (excitation maximum at 350 nm, emission maximum at 440 nm). When irradiated with the quasi-monochromatic light (over the range 325-525 nm), microspheres in which flavin pigments were prevailing showed a maximum photophosphorylating activity at 375 and 450 nm, and pteridine-containing chromoproteinoid microspheres were most active at 350 nm. The positions and the relative height of maxima in the action spectra correlate with those in the excitation spectra of the pigments, which point to the involvement of abiogenic flavins and pteridines in photophosphorylation.

Abiogenic photophosphorylation of ADP to ATP sensitized by flavoproteinoid microspheres.

A model for abiogenic photophosphorylation of ADP by orthophosphate to yield ATP was studied. The model is based on the photochemical activity of flavoproteinoid microspheres that are formed by aggregation in an aqueous medium of products of thermal condensation of a glutamic acid, glycine and lysine mixture (8:3:1) and contain, along with amino acid polymers (proteinoids), abiogenic isoalloxazine (flavin) pigments. Irradiation of aqueous suspensions of microspheres with blue visible light or ultraviolet in the presence of ADP and orthophosphate resulted in ATP formation. The yield of ATP in aerated suspensions was 10-20% per one mol of starting ADP. Deaeration reduced the photophosphorylating activity of microspheres five to 10 times. Treatment of aerated microsphere suspensions with superoxide dismutase during irradiation partially suppressed ATP formation. Deaerated microspheres restored completely their photophosphorylating activity after addition of hydrogen peroxide to the suspension. The photophosphorylating activity of deaerated suspensions of flavoproteinoid microspheres was also recovered by introduction of Fe3+-cytochrome c, an electron acceptor alternative to oxygen. On the basis of the results obtained, a chemical mechanism of phosphorylation is proposed in which the free radical form of reduced flavin sensitizer (F1H*) and ADP are involved.