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Anaphylactoid Reaction to Cisatracurium May Be Explained by Atracurium Metabolites

Rieder, J.; Gruber, G.; Bodrogi, F.; Lirk, P.; Hoffmann, G.

doi: 10.1213/00000539-200301000-00060
LETTERS TO THE EDITOR: Letters & Announcements

Department of Anesthesiology and Critical Care Medicine

University of Innsbruck

Innsbruck, Austria

To the Editor:

We read with great interest the recent report by Krombach et al. (1) about anaphylactoid reactions after cisatracurium administration to six patients and would like to comment on the possible mechanisms for these reactions.

Although atracurium toxicity has been suspected since 1987 (2) and was indicated in a clinical study by Thacker et al. (3), solid evidence of potential toxicity in human cells has only recently been established in vitro (4).

Recent literature has seen a number of case reports of anaphylactoid reactions following administration of atracurium and cis-atracurium in adults (5) as well as neonates (6). However, the underlying mechanism of action was not speculated upon.

We speculate that two mechanisms may be causative in atracurium-related anaphylactoid reactions: direct immunogenicity and acrylate-mediated immune activation.

First, atracurium and cisatracurium (5) themselves may be immunogenic. This direct activation of anaphylactoid pathways has been ascribed to direct mast cell activation by interaction of IgE and substituted ammonium moieties in the mentioned muscle relaxants (7,8).

Alternatively, activation of anaphylactic pathways has been described in connection with acrylates on polymeric membranes during hemodialysis via induction of the contact system (9). Acrylate formation by the plasma-based Hoffmann reaction has recently been described (10). Recently, we could demonstrate a strong antiproliferative effect of atracurium and cisatracurium-derived acrylate esters on human umbilical vein endothelial cells as well as in the hepatoma cell line HepG2 (4).

Therefore, the latter pathway may represent an alternative, or synergistic, road in anaphylaxis, one of the main adverse events following muscle relaxant application.

J. Rieder

G. Gruber

F. Bodrogi

P. Lirk

G. Hoffmann

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