Oxygent™ as a Top Load to Colloid and Hyperoxia Is More Effective in Resuscitation From Hemorrhagic Shock Than Colloid and Hyperoxia Alone

Abstract

Perfluorocarbon (PFC) emulsions are intravascular oxygen therapeutics that temporarily enhance tissue oxygenation in dilutional anemia. However, PFC emulsions are not resuscitation fluids because PFCs only work optimally in the presence of high O2 partial pressure (hyperoxia); moreover, because they have no oncotic potential, dosing limitations prevent their use to permanently replace large hemorrhage volumes. Our objective was to clarify whether in the presence of hyperoxia a conventional colloid therapy supplemented by PFC is more efficacious than colloid alone. To answer this question, 22 anesthetized, ventilated dogs were hemorrhaged to a mean arterial pressure of 45 mmHg and were kept at this level until a metabolic O2 debt of 120 mL kg(-1) body weight had evolved. Hyperoxia was established and dogs were randomly allocated to receive colloid (6% HES, Hydroxy Ethyl Starch shed blood volume) or colloid together with Oxygent (perflubron emulsion, 60%, w/v; Alliance Pharmaceutical Corp., San Diego, CA; single dose, 4.5 mL kg(-1); i.e., 2.7 g PFC kg body weight) in a blinded fashion. Hemodynamic and O2 transport parameters, intestinal mucosal blood flow (microspheres), and O2 partial pressure (MDO-Electrode; Eschweiler, Kiel, Germany) were measured at baseline, in shock, and during 3 h post-therapy. In the presence of hyperoxia, Oxygent improved the amount of physically dissolved O2 in plasma and increased the contribution of physically dissolved O2 to global O2 delivery (P < 0.05) and thus whole body O2 consumption when compared with colloid alone (P < 0.05). As a result, Oxygent reduced intestinal mucosal hypoxia and global O2 debt within the first hour post-therapy (P < 0.05). We conclude that under hyperoxic conditions, fluid resuscitation supplemented by Oxygent was more efficacious than colloid and hyperoxia alone. PFC temporarily enhanced intestinal mucosal tissue oxygenation during resuscitation.

Perfluorocarbon emulsion improves oxygen transport of normal and sickle cell human blood in vitro

“…In skeletal muscle, PFC improved O 2 transport after hemorrhage . In dogs, PFC increased intestinal mucosal tissue oxygenation and was also successfully used in cardiopulmonary bypass …”

Blood Substitutes

“…However, the supplementation of conventional shock-therapy (i.e., crystalloids and colloids) with PFC may be advantageous. In splenectomized dogs, Kemming and coworkers demonstrated beneficial effects on survival and tissue oxygenation attributable to the combined use of fluid resuscitation with hetastarch, hyperoxic ventilation, and infusion of 4.5 mL/kg Oxygent™ 60% [47]. The same treatment modality was found beneficial in rats subjected to hemorrhagic shock: hepatic microcirculation, tissue oxygenation, and hepatocellular energy metabolism were restored most sufficiently in PFCtreated animals when compared with colloidal fluid resuscitation alone or with the transfusion of stored RBCs [75,76].…”

Therapeutic effects of hyperoxic ventilation during shock

“…In this regard, a study of combined hyperoxic ventilation with partial fluid resuscitation in a lethal model of porcine hemorrhagic shock reported that supplementation of partial fluid resuscitation with normobaric hyperoxic ventilation improved tissue oxygenation and survival 77 . In addition, combined treatment with fluid resuscitation, perfluorocarbon and NBO was found significantly superior to each of the therapies alone in a severe canine model of hemorrhagic shock 78 . Altogether, sufficient experimental data are available to suggest that hyperoxic ventilation is a valuable adjunct to other commonly accepted modalities currently employed for resuscitation in trauma/shock.…”