Simon Faithfull | PubMed Health

PubMed2005

Oxygent as a top load to colloid and hyperoxia is more effective in resuscitation from hemorrhagic shock than colloid and hyperoxia alone.

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.

Animals↗

PubMed2002

Use of perflubron emulsion to decrease allogeneic blood transfusion in high-blood-loss non-cardiac surgery: results of a European phase 3 study.

BACKGROUND: This single-blind randomized study in general surgery evaluated the efficacy of perflubron emulsion (PFC) as an artificial oxygen carrier being used to augment preoperative acute normovolemic hemodilution to reduce and avoid transfusion of both allogeneic erythrocytes and erythrocytes from preoperative autologous donation compared with standard of care. METHODS: Subjects (N = 492) with hemoglobin concentrations of 12-15 g/dl undergoing noncardiac surgical procedures with 20 ml/kg or greater expected blood loss were randomized into two groups. Control patients were transfused intraoperatively at a hemoglobin concentration less than 8.0 +/- 0.5 g/dl or at protocol-defined, physiologic triggers. PFC-treated patients first underwent acute normovolemic hemodilution to hemoglobin of 8.0 +/- 0.5 g/dl, followed by dosing with perflubron emulsion (1.8 g/kg). When hemoglobin reached less than 6.5 +/- 0.5 g/dl, an additional 0.9-g/kg dose was given. PFC patients were transfused at hemoglobin less than 5.5 +/- 0.5 g/dl or at predefined physiologic triggers. After surgery, hemoglobin was maintained at 8.5 +/- 0.5 g/dl or greater in all patients until discharge. Efficacy endpoints included the number of allogeneic and preoperative autologous donation units transfused and the percentage of subjects avoiding transfusion. RESULTS: Both groups had similar hemoglobin concentrations at screening (13.5 +/- 1.0 g/dl) and at discharge: 10.8 +/- 1.2 g/dl (PFC) and 11.1 +/- 1.3 g/dl (control). At 24 h, more patients in the PFC group avoided allogeneic and preoperative autologous donation erythrocyte transfusions (53% vs. 43%, < 0.05), and fewer erythrocytes were transfused (1.5 +/- 4.8 vs. 2.1 +/- 3.9 units; median, 0 vs. 1 unit; P = 0.013). By day of discharge, these differences were not significant in the intent-to-treat population, but overall there were less allogeneic and preoperative autologous donation erythrocyte transfusions in the PFC group (696 vs. 846 units). In the protocol-defined target population (n = 330 subjects with blood loss > or = 20 ml/kg), significantly greater avoidance of any erythrocyte transfusion was maintained through day of hospital discharge (26% vs. 16% in the PFC and control groups, respectively; P < 0.05), and there was also a significant reduction in the number of erythrocyte units transfused (3.4 +/- 2.9 vs. 4.9 +/- 2.4 units; median 2 vs. 4 units; P < 0.001). Adverse events rates were similar in the PFC (86%) and control (81%) groups; however, more serious adverse events were reported in the PFC group (32%) than in controls (21%; P < 0.05). Overall mortality was 3%, and the difference between groups (PFC, 4% vs. controls, 2%) was not statistically significant. CONCLUSIONS: Augmented acute normovolemic hemodilution with PFC reduces transfusion needs in patients undergoing noncardiac surgical procedures with blood loss 20 ml/kg or greater.

Adult↗