Immune-Mediated Reactions to Althesin (Alphaxalone)

Abstract

Measurements of complement conversion and white cell variations were made on sequential blood samples obtained from a single volunteer following repeated administration of Althesin. The results suggest a mechanism by which a clinically significant hypersensitivity reaction to the drug might be mediated. Studies of patients receiving routine anaesthesia revealed a very high incidence of subclinical "hypersensitivity" reaction, some of which appear to be immune-mediated. These reactions occurred irrespective of whether the patients were induced with Althesin, methohexitone or propanidid.

Histamine release and hypotensive reactions in dogs by solubilizing agents and fatty acids: Analysis of various components in cremophor El and development of a compound with reduced toxicity

“…The classical work of WATKrNs and his colleagues [44] described several mechanisms of adverse reactions to cremophor El-containing anaesthetics in man, such as propanidid and althesin: involvement of complement via the classical or the alternative pathway, involvement of IgE and involvement of non-immunological mechanisms, which in our opinion may be mediated by cremophor E1 derivatives binding to mast cell receptors or acting somewhat as ionophores. One classical feature of complement activation are changes in the content of leucocytes and thrombocytes in peripheral blood.…”

Lessons for management of anaphylaxis from a study of fatal reactions

“…It was in some cases impossible to determine whether a fatal reaction had been anaphylactic (due to IgE-sensitized mast cells triggered by allergen) or anaphylactoid. Probable anaphylactoid reactions include the reactions to vitamin K (possibly due to complement activation by the polyethoxylated castor oil used as an excipient [6]). A case of fatal angioedema due to perindopril was probably due to raised tissue bradykinin concentration [7].…”

TRUE ANAPHYLAXIS TO SUXAMETHONIUM CHLORIDE: A case report

“…Repopulation of the surface of viable cells occurs from the plasma pool with IgE molecules after the adverse reaction (J. Watkins, personal communication). The degree of C3 consumption and conversion (table I) is significant but insufficient to cause the severe clinical signs encountered, making it very unlikely that this is a direct complement-mediated response as has been reported for some reactions to Althesin (Watkins, Clarke et al, 1976). Severe anaphylactoid and anaphylactic reactions to i.v.…”