Vasoactivity of Bovine Polymerized Hemoglobin (HBOC-201) in Swine With Traumatic Hemorrhagic Shock With and Without Brain Injury

Abstract

In swine with HS +/- TBI, HBOC-201 had mild to moderate vasoactivity, resulting in significant DeltaMAP responses mainly after initial infusions, no severe/adverse responses, and improved outcome. Our data suggest that use of physiologic parameters (e.g., tachycardia), in addition to hypotension to guide fluid reinfusion during HS resuscitation with HBOC-201, will minimize hypoperfusion risk and maximize potential benefit.

HBOC-201 Vasoactivity in a Phase III Clinical Trial in Orthopedic Surgery Subjects—Extrapolation of Potential Risk for Acute Trauma Trials

“…12 A similar pattern was reported with HBOC-201 in swine with HS. 17 Responses were lower in HBOC-201 subjects with preinfusion hypotension, lower preinfusion SBP even among nonhypotensive subjects, and in younger trauma and Ͻ50-year-old subpopulations. Although trends were the same as in the overall population (HBOC-201 Ͼ RBC), group differences in responses were generally narrowed in these subpopulations.…”

“…A similar pattern was reported with HBOC-201 in swine with HS. 17 Interestingly, no subjects with hypotension and younger age (trauma and Ͻ50-year-old subpopulations) had significant responses (although Ns were small). As HBOC-201 subjects with lower versus higher responses had similar cardiac AE rates, SBP ⌬ responses did not predict outcome.…”

“…4 -6,9 Any BP response can potentially mislead ambulance personnel and result in underresuscitation and hypoperfusion; but practice guidelines (inclusion of additional fluid infusion criteria [e.g., tachycardia]) should mitigate this risk. 17,19 More severe BP responses could induce ischemic events, but risk was low in the overall population, still lower in younger and hypotensive subjects, and low in hypotensive swine with HS. 17 Thus, risk of severe BP responses appears low for acute trauma trials, in which mean age is typically Ͻ40 years old.…”

“…17,19 More severe BP responses could induce ischemic events, but risk was low in the overall population, still lower in younger and hypotensive subjects, and low in hypotensive swine with HS. 17 Thus, risk of severe BP responses appears low for acute trauma trials, in which mean age is typically Ͻ40 years old.…”

Fluid Resuscitation of Uncontrolled Hemorrhage Using a Hemoglobin-Based Oxygen Carrier

“…16–22 However, vasoactivity, manifested as vasoconstriction from local scavenging of nitric oxide (NO), has hampered development for trauma use. 23 Consequently, much effort to attenuate HBOC-201’s vasoactivity is underway, mainly by modifying the molecular weight (MW) distribution and admixing NO donors such as sodium nitroglycerine (NTG). However, there is limited knowledge of the interaction between TBI-related physiological dysfunction and HBOC-based resuscitation in the prehospital setting.…”