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.
Department of Surgical Sciences, University of Wisconsin, Madison, Wisconsin 53706, USA. pipob@svm.vetmed.wisc.edu
Rebecca A
RA
Johnson
Ken T
KT
Simmons
Jonathan P
JP
Fast
Carrie A
CA
Schroeder
Robert A
RA
Pearce
Ralph M
RM
Albrecht
Sandro
S
Mecozzi
D018686:Anesthetics, Intravenous / Q000008:administration & dosage* / Q000633:toxicity; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003167:Complement Activation / Q000187:drug effects; D004285:Dogs; D004339:Drug Compounding; D004342:Drug Hypersensitivity / Q000097:blood / Q000209:etiology* / Q000276:immunology / Q000503:physiopathology; D004655:Emulsions; D005466:Fluorocarbons / Q000008:administration & dosage / Q000633:toxicity*; D006339:Heart Rate / Q000187:drug effects; D006632:Histamine / Q000097:blood; D006636:Histamine Release / Q000187:drug effects*; D007022:Hypotension / Q000139:chemically induced / Q000503:physiopathology; D007124:Immunoenzyme Techniques; D007275:Injections, Intravenous; D008738:Methyl Ethers / Q000008:administration & dosage* / Q000633:toxicity; D010316:Particle Size; D011863:Radioimmunoassay; D000077149:Sevoflurane; D013997:Time Factors
D018686:Anesthetics, Intravenous; D004655:Emulsions; D005466:Fluorocarbons; D008738:Methyl Ethers; D000077149:Sevoflurane; D006632:Histamine
Clin Toxicol (Phila). 2010 Jan;48(1):1-27
20095812
Br J Anaesth. 1970 May;42(5):419-24
5431541
Transfus Med Rev. 2004 Oct;18(4):245-56
15497125
Anesthesiology. 1969 Feb;30(2):246-7
5765387
Pharm Res. 2009 Oct;26(10):2270-9
19633820
Anesth Analg. 2006 Jan;102(1):129-34
16368817
Allergol Int. 2009 Mar;58(1):11-9
19153532
Anesthesiology. 2004 Nov;101(5):1160-6
15505452
Ther Clin Risk Manag. 2010 Oct 05;6:449-51
20957136
Cancer. 2007 Jul 1;110(1):103-11
17516438
Toxicology. 2005 Dec 15;216(2-3):106-21
16140450
Mol Ther. 2006 Feb;13(2):328-37
16275098
Anesthesiology. 2008 Oct;109(4):651-6
18813044
Anesth Analg. 1992 May;74(5):747-52
1567044
Can J Anaesth. 1995 Feb;42(2):173-6
7720163
Int J Pharm. 2008 Apr 16;354(1-2):56-62
18083313