Ethylene Oxide (ETO) as a Major Cause of Anaphylactoid Reactions in Dialysis (A review)

Abstract

Ethylene oxide (ETO), an alkylating compound of high chemical reactivity, is widely used for gas sterilization, but recently serious ETO side reactions have been recognized. With chronic ETO exposure, increased spontaneous abortion, sister chromatid exchange, and leukemia are observed. After medical use of ETO outside nephrology, contact dermatitis, cardiopulmonary shock (during cardiopulmonary surgery), allergic local reactions to ETO sterilized lenses, and anaphylactoid reactions to ETO sterilized catheters have been described. In numerous dialysis patients widespread hypersensitivity to ETO has been documented by skin prick test and ETO radioallergosorbent test (RAST). Furthermore an anaphylactoid "first-use reaction" was described in dialyzed patients, most of whom were using hollow-fiber dialyzers. After long discussions whether complement activation versus hypersensitivity is the cause of such acute anaphylactoid reactions, more recent studies using either ETO RAST or basophil degranulation tests implicate ETO hypersensitivity as their major cause. The high prevalence of sensitization to ETO and the frequency, unpredictability, and potential danger of anaphylactoid reactions to ETO lead to the conclusion that ETO sterilization of dialyzers should be discontinued, since alternative modalities of sterilization are currently available.

Sterilization Procedures and Biocompatibility

“…This difference was attributed to the polyurethane (PU) used as potting agent in the manufacture of capillary dialyzers, that acts as a reservoir for ETO, allowing its slow release along the dialysis session [8]. Similar reactions have also been described in patients exposed to hemofiltration, plasma separation (with membranes other than cuprophan) [9] and in plasma donors repeatedly exposed to ETO-sterilized tubing [2].…”

“…The bactericidal, fungical and sporocide activity is due to its alkylating properties. ETO may react with H 2 O and other compounds yielding adducts with esters, amides, amines and mercaptanes [2]. These major reactions are of importance for sterilization but also for hapten formation.…”

“…These major reactions are of importance for sterilization but also for hapten formation. ETO and its derivates are irritants for skin and mucosae, and may cause contact allergic reactions, hemolysis, coagulation abnormalities, dermatitis and respiratory tract dysfunction particularly in exposed workers [2,3].…”

OSHA's renewed mandate for Regulatory Flexibility review: In support of the 1984 ethylene oxide standard

“…EtO has also long been known to be potent allergic sensitizer [Bommer and Ritz, 1987;Bommer et al, 1985]. Most of the early studies of EtO allergenic properties were conducted on patients who had been exposed to EtO in medical devices.…”

Effect of polyflux membranes on the improvement of hemodialysis-associated eosinophilia: a case series

“…3,9 Hypersensitivity reactions to compounds such as cuprophane used in many non-biocompatible membranes have been reported. [10][11][12] By now, no special treatment has been developed for HAE, but the use of biocompatible membranes might help to manage HAE. The Polyflux membrane, made of polyamide (PA), polyarylethersulfone (PAES) and polyvinylpyrrolidone (PVP), can alleviate allergic reactions by reducing white blood cell (WBC) and complement activation, by increasing biocompatibility, and by reducing oxidative stress and cytokine release by decreasing endothelial damage during dialysis.…”