Anaesthesiologists administer several drugs while providing general anaesthesia. Many of these drugs can elicit adverse drug reactions that fall apart into two major types. First, reactions that are usually dose-dependent and related to the pharmacological properties of the drug and/or its metabolites. Second, reactions that are unrelated to the drug's pharmacological characteristics and that are less dose-dependent. These reactions comprise drug intolerance, idiosyncratic reactions and drug-induced immune-mediated allergic and nonimmune-mediated so-called pseudo-allergic or anaphylactoid reactions. The terms anaphylactic and anaphylactoid, however, have been used inconsistently in the literature. Therefore, the nomenclature task force set up by the European Academy of Allergy and Immunology (EAACI) has proposed that anaphylactic-type reactions should be reclassified into allergic anaphylaxis and nonallergic anaphylaxis. Allergic anaphylaxis being further subdivided in IgE-mediated and non-IgE-mediated reactions (1).The exact prevalence of anaphylaxis during anaesthesia is difficult to ascertain. The estimated overall frequency has been reported to vary between 1 in 3500 and 1 in 13 000 procedures in French series (2, 3) and between 1 in 10 000 and 1 in 20 000 in an Australian study (4). The clinical manifestation of these reactions is not infrequently an almost immediate generalized response with bronchospasm and hypotension. The degree of severity varies and does not allow differentiation between an IgE-mediated or non-IgE mediated reaction resulting from nonspecific mediator release (5). The mortality from these reactions is in the range from 3 to 6%, and an additional 2% of patients experience significant residual brain damage (4).Diagnosis of anaphylaxis during anaesthesia is not always straightforward. It can be hampered as a broad spectrum of different drugs can elicit heterogeneous allergic and nonallergic reactions with distinct and sometimes unclear pathological mechanisms. Problems are certainly compounded as multiple drugs need to be administered during general anaesthesia. In addition, nonanaesthesia related drugs or procedures (e.g. disinfection) are sometimes administered/performed in the perioperative period and can also be the cause of an allergic reaction.In addition, none of the available diagnostic tests demonstrates absolute accuracy. False-positive test Correct management of anaphylaxis during anaesthesia requires a multidisciplinary approach with prompt recognition and treatment of the acute event by the attending anaesthesiologist, and subsequent determination of the responsible agent(s) with strict avoidance of subsequent administration of all incriminated and/or cross-reacting compounds.However, correct identification of the causative compound(s) and safe alternatives is not always straightforward and, too often, not done.This review is not intended to discuss acute management of anaesthesia-related anaphylaxis but summarizes the major causes of anaphylaxis during anaesthesia and the di...

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Serious, and occasionally fatal, anaphylactic-like (anaphylactoid) reactions may occur when a patient is exposed to a drug for the first time. Apart from the penicillins, nothing is known of the nature of antigenic or sensitizing drug determinants and, as yet, there is no evidence for the involvement of IgE antibodies in most drug reactions. Muscle relaxants such as alcuronium have been implicated in many life-threatening anaphylactoid reactions but the mechanisms remain unclear. We have now investigated the possibility that drug-specific IgE antibodies are involved by using an alcuronium-carrier complex in a radioimmunoassay with patients' sera. Alcuronium-reactive antibodies were found in five drug-sensitive subjects and most of the antibodies cross-reacted with other muscle relaxants and with a variety of apparently structurally unrelated drugs. Structure-activity studies designed to explore the molecular basis of the antibody binding established that quaternary and tertiary ammonium ions were the complementary allergenic sites on the reactive drugs. These structures occur widely in many drugs but also in foods, cosmetics, disinfectants and industrial materials. Hence, there would seem to be ample opportunity for sensitive individuals to come into contact with and synthesize IgE antibodies to these unusual, and previously unsuspected, antigenic determinants.

Observations in 205 patients with cardiovascular manifestations of anaphylactic shock confirmed the belief that adrenaline is the drug of first choice in management and that colloid solutions are preferable to crystalloid solutions in volume replacement. Arrhythmias and elevated filling pressures are more common in patients with cardiac disease but the sympathetic response appears to override the cardiac effects of histamine in healthy patients.

Following the demonstration 25 years ago that substituted ammonium groups on neuromuscular blocking drugs (NMBDs) are the main allergenic structures recognized by IgE antibodies in the sera of some patients who experience anaphylaxis during anaesthesia, immunoassays for these drugs were quickly applied to supplement skin tests in the diagnostic assessment of suspected adverse reactions to anaesthetic agents. Many subjects who react to an NMBD do so on first exposure and this led to the speculation that the origin of allergic sensitization is an environmental agent(s) or another drug containing an ammonium ion. Direct antibody binding and hapten inhibition studies revealed that morphine, which contains a tertiary amino group, was strongly recognized by IgE in sera from anaphylactic patients and a morphine-solid phase immunoassay was found to be superior to NMBD-based assays for the detection of NMBD-reactive IgE antibodies. Extensive inhibition experiments indicate the likelihood of antibody combining site heterogeneity with recognition at the fine structural level of features additional, and adjacent to, ammonium ions. Further quantitative investigations are needed to identify these neighbouring groups on different NMBDs. Recent work has implicated the morphine analogue pholcodine as the sensitizing agent in Norway where, unlike Sweden, anaphylactic reactions to NMBDs are not uncommon and the medicament is available over-the-counter. This has led to the suggestion that allergenic sensitization to the ammonium group of pholcodine may account for the different incidences of anaphylaxis during anaesthesia in the two countries. This work is subjected to critical review and some alternative speculations on the nature and origin of the sensitizing agent(s) are presented.