Histamine Release Associated with Intravenous Delivery of a Fluorocarbon-Based Sevoflurane Emulsion in Canines

The purpose of this study was to evaluate the effectiveness of a novel fluorocarbon-based sevoflurane emulsion in dogs previously shown to produce short-term rodent anesthesia. On the basis of an unexpected allergic-type clinical reaction, we also tested the hypothesis that this type of formulation causes histamine release and complement activation. Physiological parameters, plasma histamine levels (radioimmunoassay), and complement activation (enzyme immunoassay) were quantified in response to emulsion components, including F13M5 (the emulsion's fluorocarbon-based polymer) and methoxy poly(ethylene glycol) 5000 (the polymer's hydrophilic block). Although the emulsion produced general anesthesia in dogs, they also experienced hypotension and clinical signs suggestive of an allergic-like response (i.e., vasodilation, urticaria, and pruritus upon recovery). Emulsions lacking sevoflurane failed to induce anesthesia but did elicit the allergic response. Plasma histamine levels were significantly increased following injection of micellar solutions of F13M5. Direct complement activation by the emulsion or its components was weak or absent. An allergic response leading to histamine release, likely initiated by the F13M5 component via an immunoglobulin pathway, is associated with an intravenous fluorocarbon-based emulsion of sevoflurane. Subsequently, its usefulness in medicine in its present formulation is limited. © 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:2685-2692, 2011