title: Identification of risk factors of severe hypersensitivity reactions in general anaesthesia.
abstract: BACKGROUND
  Hypersensitivity reactions to anaesthetic agents are rare but often severe, with a mortality ranging from 4 to 9% in IgE-mediated events. Identification of the risk factors may contribute to limit the incidence of these reactions. The aim of our study was to search for possible risk factors of severe perioperative hypersensitivity reactions in our study population.
  
  
  METHODS
  For this study we retrospectively reviewed data from 193 patients who experienced drug hypersensitivity reactions during general anaesthesia. The diagnostic protocol consisted of 1) history of the reaction, 2) measurement of serum baseline tryptase and specific IgE-assays for latex, beta-lactams and succinylcholine, 3) skin tests for the agents listed in the anaesthesia chart and for others likely to be safe for future use, latex, and others medications administered during the perioperative period (i.e. antibiotics), 4) subdivision of our patients on the basis of two criteria: a) grade of severity of clinical reactions according to the Ring and Messmer classification; b) results of skin tests and/or serum specific IgE-assays.
  
  
  RESULTS
  One hundred of 193 patients had reactions of grade I, 32/193 patients had reactions of grade II, 55/193 patients had reactions of grade III and 6/193 patients had reactions of grade IV. A diagnosis of IgE-mediated reaction was established in 55 cases (28.50%); the most common causes were neuromuscular blocking agents, followed by latex and beta-lactams. Severe reactions were associated with older age (p = 0.025), asthma (p = 0.042), history of hypertension (p = 0.001), intake of serum angiotensin converting enzyme inhibitor medication (p = 0.012) or serum angiotensin II antagonist (p = 0.033), higher levels of basal tryptase (p = 0.0211). Cardiovascular symptoms (p = 0.006) and history of hypersensitivity to antibiotics (p = 0.029) were more frequently reported in IgE-mediated reactions.
  
  
  CONCLUSIONS
  We confirmed the relevance of several clinical features as risk factors for anaphylactic reactions induced by anaesthetic agents: older age, asthma, hypertension and antihypertensive drugs. We observed increased levels of serum basal tryptase in severe reactions: this finding may signify that this biomarker is useful for the identification of patients at risk.
authors.affiliation: Allergology and Immunology Unit, Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: Mirone
authors.affiliation: Allergology and Immunology Unit, Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Preziosi
authors.affiliation: Allergology and Immunology Unit, Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: Ambra
authors.initials: A
authors.lastname: Mascheri
authors.affiliation: Allergology and Immunology Unit, Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Micarelli
authors.affiliation: Department of Laboratory Medicine Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Farioli
authors.affiliation: Allergology and Immunology Unit, Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: Luca G
authors.initials: LG
authors.lastname: Balossi
authors.affiliation: Allergology and Immunology Unit, Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: Joseph
authors.initials: J
authors.lastname: Scibilia
authors.affiliation: Allergology and Immunology Unit, Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: Jan
authors.initials: J
authors.lastname: Schroeder
authors.affiliation: Allergology and Immunology Unit, Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Losappio
authors.affiliation: Allergology and Immunology Unit, Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Aversano
authors.affiliation: Allergology and Immunology Unit, Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: Chrysi
authors.initials: C
authors.lastname: Stafylaraki
authors.affiliation: Service of Biostatistics, Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Nichelatti
authors.affiliation: Allergology and Immunology Unit, Niguarda Ca' Granda Hospital and Department of Clinical Science and Community Health Università degli Studi of Milan, Milan, 20162 Italy.
authors.forename: Elide A
authors.initials: EA
authors.lastname: Pastorello
keywords: Age; Anaphylaxis; Angiotensin-converting enzyme inhibitor; General anaesthesia; Hypersensitivity; Hypertension; Neuromuscular blocking agents; Risk factors; Serum tryptase; Severity