Background
We sought to determine the magnitude of the inherent inter-animal physiologic variability by automating a porcine Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) protocol ...to minimize external influences that might alter physiology and confound experimental results.
Methods
Swine (n = 42) underwent a controlled 30% blood volume hemorrhage followed by 30 minutes of REBOA (ie, ischemic phase). The animals were weaned from REBOA autonomously over 15 minutes, beginning the reperfusion phase, while continuing to provide partial flow balloon support to maintain a target proximal mean arterial pressure (pMAP) of 65 mmHg. Simultaneously, shed blood was re-transfused as part of the resuscitation efforts. Physiologic data were continuously recorded, and serum samples were serially collected. Baseline characteristics, variance in vital signs, and 8-isoprostane levels were quantified during hemorrhage, REBOA, and reperfusion phases.
Results
There was no significant difference in baseline physiology across animals (P > .05). Hemodynamic variability was highest for pMAP during the ischemic phase (P = .001) and for distal mean arterial pressure (dMAP) during the weaning/reperfusion phase (P = .001). The latter finding indicated the variable physiologic response to ischemia-reperfusion injury, as the automated balloon support required by each animal to maintain pMAP was highly variable. Circulating 8-isoprostane variance was significantly higher following the start of reperfusion compared to baseline levels (P = .001).
Discussion
Despite subjecting animals to a highly consistent ischemia-reperfusion injury through automation, we noted significant variability in the hemodynamic and biochemical response. These findings illustrate the inherent physiologic variability and potential limitations of porcine large animal models for the study of shock.
Disruption of the vascular endothelium and endothelial glycocalyx (EG) has been described after severe trauma. Plasma has been suggested to restore microvascular integrity by preservation and repair ...of the EG. We sought to evaluate whether plasma administered in a 1:1:1 ratio was associated with less endothelial marker circulation than a 1:1:2 ratio.
This is a secondary analysis of the PROPPR trial, which investigated post-traumatic resuscitation with platelets, plasma, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio. Syndecan-1, soluble thrombomodulin (sTM), and receptor for advanced glycation end products (RAGE) were quantified for each treatment group on admission and at 2 hours, 4 hours, 6 hours, 12 hours, 24 hours, 48 hours, and 72 hours. Patients were excluded if they did not survive longer than 3 hours or had data from fewer than two time points.
Three hundred eight patients in the 1:1:1 group and 291 in the 1:1:2 group were analyzed. There were no statistically significant differences in syndecan-1, sTM, or RAGE between treatment groups at any time point ( p > 0.05). Patients who developed acute respiratory distress syndrome, acute kidney injury, and death had significantly elevated biomarker expression at most time points when compared with patients who did not develop these sequelae ( p < 0.05).
Administration of FFP in a 1:1:1 ratio does not consistently affect circulation of endothelial biomarkers following significant trauma when compared with a 1:1:2 ratio. The development of post-traumatic ARDS, AKI, and death was associated with increased endothelial biomarker circulation.
Therapeutic/Care Management; Level III.
Objective: To assess lymphatic adaptations to edema, we evaluated lymph transport function in rat mesenteric lymphatics under normal and increased fluid volume (edemagenic) conditions in situ.
...Methods: Twelve rats were infused with saline (venous infusion, 0.2 ml/min/100g body weight) to induce edema. We intravitally measured mesenteric lymphatic diameter and contraction frequency, as well as immune cell velocity and density before, during and after infusion.
Results: A 10‐ and 6‐fold increase in lymph velocity (0.1‐1 mm/s) and flow rate (0.1‐0.6 µL/min), were observed post‐infusion, respectively (p<0.05). There were also increases in contraction frequency and fractional pump flow 1‐minute post‐infusion (p<0.05). Time‐averaged wall shear stress increased 10 times post‐infusion to nearly 1.5 dynes/cm2 (p<0.05). Similarly, maximum shear stress rose from 5 dynes/cm2 to 40 dynes/cm2.
Conclusions: Lymphatic vessels adapted to edemagenic stress by increasing lymph transport. Specifically, increases in lymphatic contraction frequency, lymph velocity, and shear stress were statistically significant. Although the changes in lymphatic diameter were not statistically significant, lymph pumping increased post‐infusion. These results suggest that edemagenic conditions stimulate lymph transport via increases in lymphatic contraction frequency, lymph velocity and flow. These changes, consequently, resulted in large increases in wall shear stress, which will activate nitric oxide pathways and modulate lymphatic transport function.
Grant Funding Source: NIH Grant No. R01 HL094269, NSF Graduate Research Fellowship
Red blood cell (RBC) hemolysis is one of the most common storage lesions in packed RBCs (pRBC). Older units of pRBCs, especially those > 21 days old, have increasing levels of hemolysis leading to ...increased oxidative stress and premature platelet activation. This effect can mostly be attributed to the increase of cell-free hemoglobin (Hb). Therefore, removal of cell-free Hb from pRBCs prior to transfusion could mitigate these deleterious effects. We propose a new method for the removal of Hb from pRBCs using zinc beads. Prepared Hb solutions and pRBCs were treated with zinc beads using two different protocols. UV–Vis spectrophotometry was used to determine Hb concentrations, before and after treatment. Experiments were run in triplicate and paired
t
tests were used to determine significant differences between groups. Zinc beads removed on average 94% of cell-free Hb within 15 min and 78% Hb from pRBCs (
p
< 0.0001), demonstrating a maximum binding capacity ~ 66.2 ± 0.7 mg Hb/mL beads. No differences in RBC morphology or deformability were observed after treatment. This study demonstrates the feasibility of using zinc beads for the rapid and targeted removal of Hb from pRBC units. Further investigation is needed to scale this method for large volume removal.
Traumatic brain injury (TBI) is a leading cause of death and disability in persons under age 45. The hallmark secondary injury profile after TBI involves dynamic interactions between inflammatory and ...metabolic pathways including fatty acids. Omega-3 polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (DHA) have been shown to provide neuroprotective benefits by minimizing neuroinflammation in rodents. These effects have been less conclusive in humans, however. We postulate genetic variants influencing PUFA metabolism in humans could contribute to these disparate findings. Therefore, we sought to (1) characterize the circulating PUFA response and (2) evaluate the impact of rs174537 on inflammation after TBI. A prospective, single-center, observational pilot study was conducted to collect blood samples from Level-1 trauma patients (N = 130) on admission and 24 h post-admission. Plasma was used to quantify PUFA levels and inflammatory cytokines. Deoxyribonucleic acid was extracted and genotyped at rs174537. Associations between PUFAs and inflammatory cytokines were analyzed for all trauma cases and stratified by race (Caucasians only), TBI (TBI: N = 47; non-TBI = 83) and rs174537 genotype (GG: N = 33, GT/TT: N = 44). Patients with TBI had higher plasma DHA levels compared with non-TBI at 24 h post-injury (
= 0.013). The SNP rs174537 was associated with both PUFA levels and inflammatory cytokines (
< 0.05). Specifically, TBI patients with GG genotype exhibited the highest plasma levels of DHA (1.33%) and interleukin-8 (121.5 ± 43.3 pg/mL), which were in turn associated with poorer outcomes. These data illustrate the impact of rs174537 on the post-TBI response. Further work is needed to ascertain how this genetic variant directly influences inflammation after trauma.
Transfusing platelets during massive hemorrhage is debated because of a lack of high-quality evidence concerning outcomes in trauma patients. The objective of this study was to examine the effect of ...platelet transfusions on mortality in severely injured trauma patients. This work analyzed PROPPR (Pragmatic, Randomized Optimal Platelet and Plasma Ratios) trial patients who received only the first cooler of blood products, which either did or did not contain platelets. Primary outcomes were all-cause mortality at 24 hours and 30 days and hemostasis. Secondary outcomes included cause of death, complications, and hospital-, intensive care unit (ICU)–, and ventilator-free days. Continuous variables were compared using Wilcoxon rank sum tests. Categorical variables were compared using Fisher's exact tests. There were 261 PROPPR patients who achieved hemostasis or died before receiving a second cooler of blood products (137 received platelets and 124 did not). Patients who received platelets also received more total plasma (median, 3 vs 2 U; P < .05) by PROPPR intervention design. There were no differences in total red blood cell transfusions between groups. After controlling for plasma volume, patients who received platelets had significantly decreased 24-hour (5.8% vs 16.9%; P < .05) and 30-day mortality (9.5% vs 20.2%; P < .05). More patients in the platelet group achieved hemostasis (94.9% vs 73.4%; P < .01), and fewer died as a result of exsanguination (1.5% vs 12.9%; P < .01). Patients who received platelets had a shorter time on mechanical ventilation (P < .05); however, no differences in hospital- or ICU-free days were observed. In conclusion, early platelet administration is associated with improved hemostasis and reduced mortality in severely injured, bleeding patients. This trial was registered at www.clinicaltrials.gov as # NCT01545232.
•Early platelet administration is associated with improved hemostasis and reduced mortality in severely injured, bleeding trauma patients.
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The Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) study evaluated the effects of plasma and platelets on hemostasis and mortality after hemorrhage. The pulmonary consequences of ...resuscitation strategies that mimic whole blood, remain unknown.
A secondary analysis of the PROPPR study was performed. Injured patients predicted to receive a massive transfusion were randomized to 1:1:1 versus 1:1:2 plasma-platelet-red blood cell ratios at 12 Level I North American trauma centers. Patients with survival >24 h, an intensive care unit (ICU) stay, and a recorded PaO2/FiO2 (P/F) ratio were included. Acute respiratory distress syndrome (ARDS) was defined as a P/F ratio < 200, with bilateral pulmonary infiltrates, and adjudicated by investigators.
Four hundred fifty-four patients were reviewed (230 received 1:1:1, 224 1:1:2). Age, sex, injury mechanism, and regional abbreviated injury scale (AIS) scores did not differ between cohorts. Tidal volume, positive end-expiratory pressure, and lowest P/F ratio did not differ. No significant differences in ARDS rates (14.8% vs. 18.4%), ventilator-free (24 vs. 24) or ICU-free days (17.5 vs. 18), hospital length of stay (22 days vs. 18 days), or 30-day mortality were found (28% vs. 28%). ARDS was associated with blunt injury (OR 3.61 1.53-8.81 P < 0.01) and increasing chest AIS (OR 1.40 1.15-1.71 P < 0.01). Each 500 mL of crystalloid infused during hours 0 to 6 was associated with a 9% increase in the rate of ARDS (OR 1.09 1.04-1.14 P < 0.01). Blood given at 0 to 6 or 7 to 24 h were not risk factors for lung injury.
Acute crystalloid exposure, but not blood products, is a potentially modifiable risk factor for the prevention of ARDS following hemorrhage.
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