title: Use of perflubron emulsion to decrease allogeneic blood transfusion in high-blood-loss non-cardiac surgery: results of a European phase 3 study.
abstract: 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.
authors.affiliation: Institute of Anesthesiology, UniversitätsSpital Zürich, Zürich, Switzerland.
authors.forename: Donat R
authors.initials: DR
authors.lastname: Spahn
authors.forename: Klaus F
authors.initials: KF
authors.lastname: Waschke
authors.forename: Thomas
authors.initials: T
authors.lastname: Standl
authors.forename: Johann
authors.initials: J
authors.lastname: Motsch
authors.forename: Léone
authors.initials: L
authors.lastname: Van Huynegem
authors.forename: Martin
authors.initials: M
authors.lastname: Welte
authors.forename: Hans
authors.initials: H
authors.lastname: Gombotz
authors.forename: Pierre
authors.initials: P
authors.lastname: Coriat
authors.forename: Lev
authors.initials: L
authors.lastname: Verkh
authors.forename: Simon
authors.initials: S
authors.lastname: Faithfull
authors.forename: Peter
authors.initials: P
authors.lastname: Keipert
mesh_terms: D000328:Adult; D016063:Blood Loss, Surgical; D004655:Emulsions; D005060:Europe; D005260:Female; D005466:Fluorocarbons / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D006842:Hydrocarbons, Brominated; D007432:Intraoperative Period; D008297:Male; D008875:Middle Aged; D011300:Preoperative Care / Q000379:methods*
chemical_list: D004655:Emulsions; D005466:Fluorocarbons; D006842:Hydrocarbons, Brominated; C003072:perflubron