• Br J Anaesth · Jul 2019


    Comparative epidemiology of suspected perioperative hypersensitivity reactions.

    Perioperative hypersensitivity reactions vary greatly between countries both in incidence and causative agents.

    • Paul Michel Mertes, Didier G Ebo, Tomaz Garcez, Michael Rose, Vito Sabato, Tomonori Takazawa, Peter J Cooke, Russell C Clarke, Pascale Dewachter, Lene H Garvey, Anne B Guttormsen, David L Hepner, Phil M Hopkins, David A Khan, Helen Kolawole, Peter Kopac, Mogens Krøigaard, Jose J Laguna, Stuart D Marshall, Peter R Platt, Sadleir Paul H M PHM Department of Anaesthesia, Sir Charles Gairdner Hospital, Perth, Western Australia, Australia; Anaesthetic Allergy Referral Centre of Western Austral, Louise C Savic, Sinisa Savic, Gerald W Volcheck, and Susanna Voltolini.
    • Department of Anesthesia and Intensive Care, Hôpitaux Universitaires de Strasbourg, Nouvel Hôpital Civil, Strasbourg, France. Electronic address: paul-michel.mertes@chru-strasbourg.fr.
    • Br J Anaesth. 2019 Jul 1; 123 (1): e16-e28.

    AbstractSuspected perioperative hypersensitivity reactions are rare but contribute significantly to the morbidity and mortality of surgical procedures. Recent publications have highlighted the differences between countries concerning the respective risk of different drugs, and changes in patterns of causal agents and the emergence of new allergens. This review summarises recent information on the epidemiology of perioperative hypersensitivity reactions, with specific consideration of differences between geographic areas for the most frequently involved offending agents.Copyright © 2019. Published by Elsevier Ltd.

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    This article appears in the collection: Anaphylaxis to Rocuronium in Australia & New Zealand.



    Perioperative hypersensitivity reactions vary greatly between countries both in incidence and causative agents.

    Daniel Jolley  Daniel Jolley

    This thorough review of the global epidemiology of perioperative hypersensitivity (POH), reflects our increasing awareness that anaphylaxis varies geographically.


    Reported incidence ranges from 1 in 18,600 to 1 in 353, although NAP6 (UK) and French studies independently estimate life-threatening anaphylaxis at 1 in 10,000.


    Anaphylaxis mortality was generally ~4% (UK, France, USA, Japan), although Western Australian data estimated a lower range of 0-1.4%.

    Causal agents

    Implicated agents commonly include neuromuscular blocking drugs (1st or 2nd commonest in most studies), although the higher incidence seen with specific NMBDs (eg. Sux and Roc) appears to occur in some regions but not others. Pholcodine has been implicated as causative in these regional differences.

    Sugammadex has increasingly been implicated as a cause of POH, though notably also with regional variation. A dose-related effect has also been reported.

    Antibiotics are an increasingly common cause of POH, in particular β-lactams. Nevertheless, ‘pan-β-lactam allergy’ is probably rare, and some examples like cefazolin, have limited cross-reactivity.

    “Cefazolin does not share an R1 and R2 group with any other β-lactam...”

    Latex POH is declining, while chlorhexidine is increasing (9% in NAP6, with significant regional variability), albeit often as a ‘hidden’ precipitant.

    Surgical dyes (patent blue V, isosulfan blue, methylene blue) are also increasingly common causes of POH (4th most common in NAP6 (~1 in 7,000), 3rd in France).

    Less common POH causes include povodine-iodine and colloids.

    Hypnotics, local anaesthetic, aprotinin, protamine and NSAIDs are very uncommon-to-rare causes of POH. Opioids are sometimes implicated via the MRGPRX2 receptor, although true opioid IgE-mediated hypersensitivity is very rare.


    The wide geographic variations in anaphylaxis incidence and causation reveal a complex interplay of genetics and environment, along with our evolving understanding of the complexity of anaphylaxis.

    Go deeper...

    Read Florvaag & Johansson’s seminal article The Pholcodine Story for an intriguing story of geographic POH differences.

    Daniel Jolley  Daniel Jolley

    “Patients suffering from anaphylaxis to succinylcholine crossreact with cis-atracurium in 10% of cases and with rocuronium in 20% of cases. Cross-sensitivity is most frequently observed with rocuronium and less frequently with cis-atracurium.”

    Daniel Jolley  Daniel Jolley


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