Secondary Logo

Journal Logo

Allergic reactions occurring during anaesthesia

Mertes, P. M.; Laxenaire, M.-C.

European Journal of Anaesthesiology: April 2002 - Volume 19 - Issue 4 - p 240-262
Review
Free
SDC

Anaphylactic reactions to anaesthetic and associated agents used during the perioperative period have been reported with increasing frequency in most developed countries. Any drug administered in the perioperative period can potentially produce life-threatening immune-mediated anaphylaxis. Most published reports on the incidence of anaphylaxis come from France, Australia, the UK and New Zealand. These reflect an active policy of systematic clinical and/or laboratory investigation of suspected immune-mediated reactions. The estimated incidence of anaphylaxis ranges from 1 : 10 000 to 1 : 20 000. Muscle relaxants (69.1%) and latex (12.1%) were the most frequently involved drugs according to the most recent French epidemiological survey. Clinical symptoms do not afford an easy distinction between immune-mediated anaphylactic reactions and anaphylactoid reactions resulting from direct non-specific histamine release. Moreover, when restricted to a single clinical symptom, anaphylaxis can easily be misdiagnosed. Pre- and postoperative investigation must be performed to confirm the nature of the reaction, the responsibility of the suspected drugs and to provide precise recommendations for future anaesthetic procedures. These include plasma histamine, tryptase and specific IgE concentration determination at the time of the reaction and at skin tests 6 weeks later. In addition, since no specific treatment has been shown reliably to prevent the occurrence of anaphylaxis, allergy assessment must be performed in all high-risk patients. Treatment of anaphylaxis is aimed at interrupting contact with the responsible antigen, inhibiting mediator production and release, and modulating the effects of released mediators. It must be initiated as quickly as possible and relies on widely accepted principles. Finally, the need for proper epidemiological studies and the relative complexity of allergy investigation should be underscored. They represent an incentive for further development of allergo-anaesthesiology clinical networks to provide expert advice for anaesthetists and allergologists.

CHU de Nancy, Hôpital Central, Département d'Anesthésie-réanimation, Nancy, France

Correspondence to: M.-C. Laxenaire, Département d'Anesthésie-réanimation, CHU de Nancy, Hôpital Central, 29 Avenue de Lattre de Tassigny, F-54035 Nancy Cedex, France. E-mail: mc.laxenaire@chu-nancy.fr; Tel: +33 383 85 15 31; Fax: +33 383 85 10 39

Accepted for publication September 2001 EJA 825

Back to Top | Article Outline

Introduction

Although our understanding of allergic reactions during anaesthesia has substantially increased over the past 30 yr, they remain a major cause of concern to anaesthetists. Anaphylaxis is an acute allergic reaction resulting primarily from the rapid antigen-induced, usually IgE-dependent release of potent, pharmacologically active mediators from tissue mast cells and peripheral blood basophils. Anaphylactic reactions may be exacerbated in severity or prolonged in duration by mediators derived from these cells or from other secondary recruited inflammatory cells. These reactions differ from 'anaphylactoid reactions' that are clinically indistinguishable from anaphylaxis but are triggered independently of IgE antibody.

Since the initial report describing an anaphylactic reaction to succinylcholine [1], followed by clinical observations reported by Fisher [2], Sigiel and colleagues [3] and Vervloet and colleagues [4], increasing interest has focused on immune-mediated reactions occurring during anaesthesia. Moreover, in light of the increasing number of anaesthetic drugs, the need for confirmation and quantitative risk assessment of suspected rare serious adverse reactions requiring precise epidemiological studies [5] has continually been reinforced. In addition, awareness of the constant changes in anaesthetic practice has led to elaboration of a growing number of practice guidelines concerning the diagnosis, high-risk group identification and management of anaphylaxis [6-11].

Back to Top | Article Outline

Mechanism

The term 'anaphylaxis' was introduced in 1902 by Charles Richet and Paul Portier to describe the hypersensitivity reactions they observed in dogs after repeated injections of sea anemone toxin [12]. In immunological terms, anaphylaxis is an example of an immediate Type 1 hypersensitivity reaction. Most cases are IgE or rarely IgG mediated. The typical sequence of events in immediate hypersensitivity begins with the production of IgE by B-cells in response to initial exposure to an antigen. These antibodies bind to specific Fc receptors on the surface of effector cells such as mast cells and basophils. The interaction of reintroduced antigen with the bound IgE leads to activation of these cells and the release of various mediators [13]. The mediators are usually classified as preformed or newly synthesized. They include histamine from mast cells and basophils, and tryptase from mast cells [14-16]. The substances are responsible for the clinical manifestations of immediate hypersensitivity. Release is produced by cellular activation and transduction triggered by the bridging of IgE-receptor complexes with allergens. The magnitude of degranulation is influenced by the affinity of a given drug for cell-bound IgE antibodies as well as by their number on the cell surface. It is estimated that the human basophil contains 40 000-100 000 IgE antibody receptors. Basophils and mast cells bind IgE via a high-affinity receptor (FcεRI), whereas lymphocytes, eosinophils and platelets bind them via a low-affinity receptors (FcεRII) triggering the release of further mediators including kinins, prostaglandins, leukotrienes, serotonin or eosinophil cationic protein [17].

Most anaesthetic drugs such as muscle relaxants or opioid derivatives are low molecular weight molecules and are considered as haptens. As such, they are incapable of inducing the production of drug-specific antibodies by themselves. Consequently, previous conjugation of the native drug or one of its degradation products with some protein carrier and processing by professional antigen-presenting cells such as dendritic cells before presentation of peptides on the cell surface in close association with a Class I or II histocompatibility molecule, is usually regarded as the initial step of sensitization [18-20]. Direct interaction with proteins present on the surface of the dendritic cell, as reported for sensitizing metal and some antibiotics, and Class II histocompatibility molecular interactions, should also be given consideration [21-23].

Although antigen presentation by dendritic cells is regarded as an essential step for induction of an immune response in modern immunology, the elicitation of an immediate IgE-mediated reaction to the same drug is influenced by different immunochemical requirements. In anaphylaxis, mast cells and basophils are activated by the cross-linking of FcεRI molecules. This is thought to occur by the binding of multivalent antigens to the attached molecules. This could be a possible explanation for the increased number of anaphylactic reactions to neuromuscular-blocking agents, in comparison with other drugs used during anaesthesia. With respect to muscle relaxants, the main antigenic determinants involved in the generation of specific IgE antibodies are substituted ammonium ions. This was initially demonstrated by Baldo and Fisher [24]. As a result, it has been hypothesized that most neuromuscular blocking agents that bear two similar quaternary ammonium ions per molecule are capable of bridging IgE antibodies and eliciting anaphylaxis. In this regard, the flexibility of the chain between the ammonium ions as well as the distance between the quaternary ammonium ions might be of importance during the elicitation phase of anaphylaxis [25,26]. Flexible molecules such as succinylcholine can stimulate sensitized cells more strongly than rigid molecules (e.g. pancuronium). The relative affinities of the various muscle relaxants to their corresponding IgEs may also play a role. This also explains the cross-reactivity between the different muscle relaxants observed with IgE antibodies of most patients, and initially evidenced by skin testing [27,28]. This cross-reactivity, however, was only observed in 70% of patients presenting with anaphylaxis to muscle relaxants [29]. In addition to the above-mentioned steric considerations, which could explain why two muscle relaxants do not necessarily behave similarly, further hypotheses have been proposed. In some cases, the antigenic determinant may either correspond to the quaternary ammonium epitope or extend to an adjacent part of the molecule. Another rare possibility might be that IgE antibodies could be complementary to structures other than the ammonium group [30].

The main antigenic determinants involved in the generation of specific IgE antibody towards other anaesthetic drugs has also been defined. Two antigenic determinants have been identified in the thiopental molecule: the secondary pentyl and ethyl groups attached in position 5 of the pyrimidine ring nucleus and the thiol region on the opposite side [30,31]. The antigenic determinant on morphine comprises the methyl-substitute attached to the N-atom and the cyclohexenyl ring with a hydroxyl group at carbon 6. Cross-reactivity between morphine, codeine and other narcotics has been reported [32].

Finally, 240 potentially allergenic proteins have been identified in processed latex products. Seven sensitizing proteins have been identified or cloned and assigned allergen designation Hev b1-b7 [33-36]. A 14-kD protein (rubber elongation factor) is one of the major allergens responsible for allergic reactions among healthcare workers, and a 27-kD protein has been implicated among several vulnerable patient populations [37,38]. Hevein [39], pro-hevein [40], latex lysosome and rubber elongation factor [41] are other potent implicated allergens.

In some instances, IgE-mediated anaphylactic reactions have been reported at the first known contact with an incriminated drug. This suggests a possible cross-reaction with IgE antibodies generated by previous contact with apparently unrelated chemicals. This is a particularly attractive hypothesis in cases where patients react to relatively small and ubiquitous epitopes such as a quaternary ammonium group [21]. The latter is the case of neuromuscular blocking agents [24]. Such a hypothesis has been proposed for adverse reactions to neuromuscular blockers and IgE antibodies generated towards acetylcholine, different membrane phospholipids or food lecithins from soy or egg [42]. Similar observations have been made concerning anaphylactic reactions to latex in patients with a history of food allergy to different fruits (avocado, kiwi, banana, fig, chestnut, hazelnut, sweet pepper, melon, pineapple, papaya). They contain several proteins similar or identical to those found in latex [43-58].

Back to Top | Article Outline

Epidemiology

The observation of possible non-specific histamine release triggered by compounds having a simple chemical structure [59] has led to intense debate about the real nature of adverse reactions associated with anaesthesia during symposia organized in France, the UK and Germany [60-66]. The concept of shock related to non-specific histamine release by various anaesthetic substances was supported by many studies carried out by Lorenz and colleagues [67,68]. However, since the first report of an anaphylactic reaction to succinylcholine [1], followed by clinical observations reported by Fisher [2], Sigiel and colleagues [3] and Vervloet and colleagues [4], increasing interest has been focused on immune-mediated reactions occurring during anaesthesia. The development of skin tests [69-71] and the identification by Baldo and Fisher [24] of the particular role played by quaternary ammonium ions on specific IgE production led to the recognition of the frequent implication of muscle relaxants in anaphylaxis during anaesthesia [72].

Most reports on the incidence of anaphylaxis originate in France [29,73-76], Australia [2,77-79], the UK [80-84] and New Zealand [69,85]. They reflect an active policy of systematic clinical and/or laboratory investigation of anaphylactoid reactions suspected to be mediated by an immune mechanism. Anaphylactic reactions have also been reported for smaller series in the USA [86,87]. Nevertheless, the true incidence of anaphylactic reactions and their associated morbidity/mortality remain poorly defined. This is due to uncertainties over reporting accuracy and exhaustiveness. This is illustrated by the differences observed between reports from various developed countries. First, the clinical reaction must be recognized and it should be emphasized that patients experiencing anaphylaxis during anaesthesia present with a variety of signs and that these may not appear all at once. In addition, some debate remains about the interpretation and significance of skin and laboratory tests usually required to distinguish between anaphylactic and anaphylactoid reactions. Finally, there are often difficulties in obtaining valid data on the number of patients exposed to the risk in the population from which reactions are reported. With these limits in mind, the estimated incidence of anaphylaxis was 1:10 000-20 000 in Australia in 1993 [78] and 1:13 000 in France in 1996 [29]. Although rare, these may lead to death, even when appropriately treated [29,88], with a mortality rate ranging from 3.5% [89] to 4.7% [90].

The prevalence of the risk of anaesthetic anaphylaxis in the overall population, which corresponds to the proportion of patients who would respond, if exposed to antigenic anaesthetic substances remains poorly defined. Skin tests and/or specific IgE assays performed on the general population could estimate it. However, their clinical significance is questionable. If positive, they reflect an IgE-dependent sensitivity but do not necessarily indicate that an allergic reaction will occur. Nevertheless, the prevalence of allergy to anaesthetic drugs is probably higher than the incidence of reactions, because patients undergoing anaesthesia do not necessarily receive the drug to which they are allergic.

The prevalence of muscle relaxant sensitivity, based on skin test positivity and/or detection of specific IgE to quaternary ammonium ions, shows wide variation. A positive reaction in 9.3% of the general population has been reported [91], with extremes ranging from 1.6% in patients with no history of atopy and/or drug allergy to 16% in patients presenting these risk factors [92,93]. This contrasts with the incidence of anaphylaxis to neuromuscular blocking agents, which has been estimated as 1:6500 for anaesthesia where a muscle relaxant is included in the anaesthetic protocol [29].

The prevalence of latex sensitization, a major cause of anaphylaxis during anaesthesia, varies depending on the population studied. As with all allergy-causing substances, the greater the exposure in a given population, the greater the number of sensitized individuals. Nevertheless, significant differences have been reported. The prevalence of latex sensitization in the literature has been reported to vary from approximately 1 to 6.6% [94,95], reaching 15.8% in anaesthesiology staff [96]. However, as previously mentioned, this IgE-dependent sensitivity does not necessarily indicate that an allergic reaction will occur in case of exposure to latex.

Back to Top | Article Outline

Causative agents

Drugs

Muscle relaxants. Among the drugs and other agents involved in anaphylaxis, muscle relaxants are most frequently involved, with a range of 50-70% [29,84,86,87,97-99](Fig. 1). In France the incidence of anaphylaxis to muscle relaxants was estimated at 1:6500 anaesthetic procedures involving a muscle relaxant in 1996 [29]. Anaphylactic reactions have been reported for all neuromuscular blocking agents, even with recently commercialized substances [29,99-111]. In most series, succinylcholine appears to be more frequently involved [74,76,112], with some differences reflecting variations in anaesthesiological practices from one country to another [13,99]. In the French survey conducted between 1 January 1997 and 31 December 1998, the percentage of anaphylactic reactions observed with each drug was compared with the estimated number of patients who effectively received these drugs over the study period [99]. The results derived from such estimates should, however, be carefully contemplated. However, they indicate that succinylcholine and rocuronium seemed to be more frequently involved. Vecuronium and pancuronium followed them whereas atracurium was the least frequently involved (Fig. 2). It should also be noted that in this series, anaphylaxis to a neuromuscular blocking agent was observed in 48 patients (14.7%) with no history of anaesthesia, and, as a consequence, no previous administration of any muscle relaxant.

Figure 1

Figure 1

Figure 2

Figure 2

Hypnotics. The estimated incidence of anaphylactoid reactions with thiopental was estimated as 1:30 000 [80]. It was suggested that most of the generalized reactions were related to its ability to elicit direct leukocyte histamine release [113]. However, there is evidence for IgE-mediated anaphylactic reactions based on skin tests and a specific IgE assay [114-117]. Although the radioimmunoassay developed for the detection of antibodies that react with thiopental is a valuable aid in confirming the diagnosis of Type I allergy to this drug, its use requires some specific consideration. IgE antibody formed in patients who react to a neuromuscular blocking agent could cross-react in vitro with the thiopental solid phase. In this case, however, thiopental does not inhibit the binding of these antibodies to the thiopental solid phase but inhibition is observed with the neuromuscular blocking agent. This allows one to distinguish between sensitization to thiopental and neuromuscular blocking drugs [30,31,118,119].

Ever since Cremophor EL (used as a solvent for some non-barbiturate hypnotics) has been avoided, many previously reported anaphylactoid reactions have disappeared. Although less frequent, anaphylaxis to all induction agents has been observed [13,120]. In the last French survey, five cases to thiopental, 10 to propofol and three to midazolam were recorded [99](Fig. 1), whereas no anaphylactic reaction to etomidate and ketamine was observed.

Opioids. Reactions to morphine, codeine phosphate, meperidine, fentanyl and its derivatives are uncommon [32]. Because of their direct histamine-releasing properties, distinction between anaphylaxis and non-immune-mediated histamine release is not always easy [121,122]. Hapten inhibition studies performed in the serum of a subject who experienced an anaphylactic reaction following the administration of papaveretum [123] has led to the identification of the allergic determinant (cyclohexenyl ring with a hydroxyl group at C-6 and methyl substituent attached to the N atom) involved in IgE binding [30]. Only seven cases were recorded in the last 2-yr epidemiologic survey in France (morphine = 1, fentanyl = 4, sufentanil = 2) [99](Fig. 1.).

Local anaesthetics. Allergic reactions to local anaesthetics are rare despite their frequent use. It is estimated that <1% of all reactions to local anaesthetics have an allergic mechanism [76,124,125]. Inadvertent intravascular injection leading to excessive blood concentrations of the local anaesthetic, or systemic absorption of epinephrine that was combined with the local anaesthetic, are by far the most common causes of adverse reactions produced by these drugs. In a series by Fisher and Bowey [125] that reports the results of an investigation conducted in 208 patients with a history of allergy to local anaesthetics over 20 yr, four patients were reported to have had an immediate allergy, and four patients had delayed allergic reactions.

Although severe anaphylactic reactions have been reported with both types of local anaesthetics [126-129], ester local anaesthetics, having a benzoic acid ring in their structure and the capability of producing metabolites related to para-aminobenzoic acid [130-132], are more likely than amide local anaesthetics to provoke an allergic reaction. Allergy to local anaesthetics may also be due to methyl-paraben [130-133], paraben [134] or metabisulphites [135,136] used as preservatives in commercial preparations.

Non anaesthetic drugs. Antibiotics are commonly administered perioperatively and can cause allergic reactions. A discussion of allergic reactions to antibiotics is beyond the scope of this review. However, their frequency has increased over the last 20 yr. They account for between 2 and 8% of reported anaphylactic reactions [99,112], cephalosporin being most commonly incriminated in Australia, whereas penicillins remain most frequently involved in France. Vancomycin, which is increasingly used for prophylaxis, has also been incriminated in some instances [137]. However, in most cases, the adverse reactions observed are related to the chemically mediated red-man syndrome associated with rapid vancomycin administration [138-140].

Protamine, whose use to reverse heparin anticoagulation has increased over the last two decades, has also been incriminated [76,103,141]. Reactions may involve a number of mechanisms including IgE, IgG and complement [142-145].

Aprotinin, a naturally occurring serine protease inhibitor, has found widespread applications either by the i.v. route or as a component of biological sealants, because of its ability to decrease blood loss and, as a consequence, transfusion requirements. Anaphylactic reactions are mediated by IgG and IgE antibodies [146]. The risk of anaphylactic reactions has been estimated as between 0.5 and 5.8%. Patients previously treated with this drug present an increased risk [147-149].

Back to Top | Article Outline

Perioperative exposures to agent other than to drugs

Latex. Allergy to natural rubber latex, which contains a complex mixture of water-soluble plant proteins, has become a major source of concern in clinical practice. It is the second most common cause of anaphylaxis during anaesthesia in the general population. However, in children subjected to numerous operations, particularly those suffering from spina bifida, it is the primary cause of anaphylaxis [150,151]. Most patients are sensitized to proteins originating from rubber tree sap (Hevea brasiliensis) present in products made from latex, such as gloves, catheters and various medical or non-medical products containing natural rubber. Latex exposure can occur as a result of contact with the skin or mucous membranes, with inhalation, ingestion and parenteral injection or with wound inoculation. The incidence of allergy to latex has rapidly increased, rising from 0.5% before 1980 to 19% in 1994 in France [76]. However, in the last French survey, latex sensitization was held responsible for 12.1% of recorded cases [99](Fig. 1). These results appear to be somewhat encouraging. They seem to indicate that increasing awareness of the risk of latex sensitization in children with spina bifida [152,153] or healthcare workers [154,155], combined with the efficacy of surgery in a latex-safe environment [156,157], could be responsible for the decrease of anaphylaxis to latex we observed.

Colloids. All synthetic colloids have been shown to produce clinical anaphylaxis. The overall incidence of reactions has been estimated to range between 0.033% [158] and 0.22% [75]. Although direct release of histamine has been reported with urealinked gelatin [159], evidence for IgE-mediated adverse reactions to gelatin has been reported [75]. In addition, adverse reactions to urea-linked gelatin (0.852%) seem to be more frequent than with modified fluid gelatin (0.338%) [75], whereas IgG-mediated adverse reactions to hydroxyethyl starch are uncommon [160-163]. Adverse reactions to dextrans were estimated as 0.275%, when it was 0.099% for albumin and 0.058% for hydroxyethyl starch solutions [75]. Eleven anaphylactic reactions to gelatin and two reactions to hydroxyethyl starch solutions were reported in the last French survey of anaphylaxis during anaesthesia [99](Fig. 1).

Back to Top | Article Outline

Clinical features

The intensities of allergic reactions show striking variation from one patient to another. Manifestations may range from mild non-life-threatening anaphylaxis to severe anaphylactic shock and death [13,78,99,164].

The onset and severity of the reaction are related to the mediator's specific end organ effects. Consequently, the difference between anaphylactoid and true anaphylactic reactions cannot be made on clinical grounds alone. IgE-dependent anaphylaxis was evident in 53% of cases [29] in a recent study involving patients investigated for an anaphylactoid reaction during anaesthesia. Clinical symptoms reported in patients with a true anaphylactic reaction and in those presenting with non-IgE-mediated anaphylactoid reactions were similar. However, when a classification based on symptom severity was applied (Table 1)[158], clinical manifestations were more severe in patients with documented anaphylaxis. Nevertheless, some cases corresponding to true IgE-mediated anaphylactic reactions were classified as Grade I or II. As a result, any suspected anaphylactoid reaction occurring during anaesthesia should be thoroughly investigated to establish a precise diagnosis and appropriate recommendations.

Table 1

Table 1

Anaphylaxis may occur at any time during anaesthesia and may progress slowly or rapidly. Ninety per cent of reactions appear within minutes after the i.v. injection of anaesthetic products or antibiotics. Alertness is essential because reactions may be well established before they are noticed. The most commonly reported initial features are pulselessness, a difficulty in lung inflation and desaturation [103]. In our experience, a decreased end-tidal CO2 expiration is also of valuable diagnostic interest. If the signs appear later during the maintenance of anaesthesia, they suggest an allergy to latex or volume expanders [75,165,166]. Latex allergy should also be considered when gynaecological procedures are performed. Particles from obstetricians' gloves, which accumulate in the uterus during obstetrical manoeuvres, could suddenly be released into the systemic blood flow following oxytocin injection [29,167]. Anaphylactic reactions to antibiotics have also been reported following removal of a tourniquet during orthopaedic surgery [168,169].

Factors that influence allergic reaction symptom severity in the sensitized individual include the distribution and reactivity of sensitized mast cells and basophils, individual organ susceptibility, released mediators and the endogenous response they elicit [170]. Anaphylaxis commonly involves the skin, cardiovascular and respiratory systems, as well as virtually any system, including the gastrointestinal, central nervous and genitourinary systems. The most recent French epidemiological survey, conducted between January 1997 and December 1998, involved 477 patients having experienced a true anaphylactic reaction during anaesthesia and most adverse reactions were of Grades II (22.9%) or III (62.6%), whereas only 10.1% of Grade I and 4.4% of Grade IV cases were recorded. Interestingly, in this series, reactions to neuromuscular blocking agents were more severe than those to latex. Cutaneous symptoms were present in 69.6% of cases (n = 332), angio-oedema in 11.7% (n = 56), bronchospasm in 44.2% (n = 211), arterial hypotension in 17.8% (n = 85), cardiovascular collapse in 53.7% (n = 256), bradycardia in 2.1% (n = 10) and cardiac arrest in 4% (n = 19) [99]. No difference in the severity of clinical symptoms was observed with regards to gender, history of atopy, asthma and food or drug intolerance. However, a significant association between the onset of clinical bronchospasm and a history of atopy or asthma was observed.

Clinical features may occur as an isolated condition [29,78,99,171]. Therefore, an anaphylactic reaction restricted to a single clinical symptom (e.g. bronchospasm, tachycardia with hypotension) can easily be misdiagnosed because many other pathological conditions may present identical clinical manifestations [13]. In mild cases restricted to a single symptom, spontaneous recovery may be observed even in the absence of any specific treatment. However, it should be kept in mind that under such circumstances, the lack of a proper diagnosis and appropriate allergologic assessment could lead to fatal re-exposure [172]. In our last survey, cardiovascular symptoms (hypotension or cardiovascular collapse) were the sole features in 10.5% (n = 50), bronchospasm in 3.2% (n = 15) and cutaneous symptoms in 7.8% (n = 37) of cases [99].

In most cases, after adequate treatment, clinical signs regress within 1 h without sequelae. However, in some cases, bronchospasm can be particularly severe and resistant to treatment, with a risk of cerebral anoxia. Prolonged inotropic support might also be required in some patients. Moreover, previous treatment by β-adrenoreceptor blocking agents is a potential risk factor explaining a lack of tachycardia, as well as resistance of arterial hypotension to adrenaline [164].

Back to Top | Article Outline

Risk factors

The potential severity of anaphylaxis during anaesthesia underscores the interest of developing a rational approach to reduce its incidence by identifying potential risk factors before surgery. With respect to drug allergy, different items such as gender, previous general anaesthesia, atopy and other drug allergies should be taken into account. Special attention should also be paid in case of allergy to latex.

Back to Top | Article Outline

Gender

A female predominance has been demonstrated in perioperative anaphylactic reactions, particularly those concerning allergic reactions to muscle relaxants with a female: male ratio ranging from 8:1 to 4:1 in some series [78,173]. In the last French epidemiological survey, it was 2.7:1 [99]. This difference was not related to an increase in female exposure to neuromuscular blocking agents. It persists even if the gender ratio (1.1 female:1.0 male) of anaesthetized patients as established by the French survey of anaesthesia is taken into account [174]. Similarly, a female predominance was observed with respects to latex sensitization. This does not, however, imply any need for systematic allergy investigation in females before anaesthesia.

Back to Top | Article Outline

Age

Children who have undergone many operations, in particular those suffering from spina bifida, are considered at an increased risk for latex sensitization [6,10,150-152,175]. This increased risk has not been confirmed in adult patients repeatedly exposed to latex [176,177]. In addition, in the last French epidemiological survey of anaphylaxis during anaesthesia, a significant difference was observed regarding the distribution of anaphylaxis to latex according to age ranges. It was significantly different from those observed with neuromuscular blocking agents, with a higher incidence in the younger age ranges [99]. On the contrary, although the peak incidence of anaphylaxis to neuromuscular blocking agents was observed in the fourth decade in females and in the fifth decade in males, anaphylaxis was reported both in young and in elderly patients.

Back to Top | Article Outline

Atopy

Atopy is a hereditary predisposition in which subjects synthesize IgE antibodies to various allergens introduced into the body via natural routes. It has long been considered a risk factor for sensitization to muscle relaxants, in light of the high number of atopic patients found in early studies of anaphylactic shock during anaesthesia, when atopy was defined on clinical grounds alone. However, when confirmed by specific immunological tests, atopy does not appear to be a significant risk factor for muscle relaxant sensitivity [91,93,178]. A history of atopy and/or asthma has a very low specificity and sensitivity is a predictor of anaphylactic reactions. Moreover, it is considered to have an unacceptably high false-alarm rate [103,179]. Nevertheless, one should bear in mind the fact that basophils of atopic patients release histamine more readily [180,181]. As a consequence, it could be a risk factor for histamine release in case of administration of known histamine-releasing drugs such as atracurium, mivacurium, propofol or gelatin [182,183].

Back to Top | Article Outline

History of drug allergy

Allergy to anaesthetic agents is the first factor to consider. Any unexplained life-threatening reaction during a previous anaesthetic might be an allergic reaction, and as such is a major risk factor for a future reaction if the responsible drug is administered again [13]. Moreover, because of the difficulties inherent in the clinical assessment of anaphylaxis and possible cross-reactions, determination of the patient's allergic status should be performed in case of any unexplained reaction to general or local anaesthetics [184].

Previous exposure does not seem to be a risk factor for reaction to muscle relaxants, and anaphylaxis to neuromuscular blocking agents has been observed in the absence of any prior general anaesthesia and, consequently, in the absence of prior administration of any of these agents [99]. However, a documented anaphylactic reaction to a muscle relaxant is a positive risk factor for a renewed shock if a muscle relaxant, even if a recent muscle relaxant to which the patient has never been exposed, is administered. The high incidence of cross-anaphylaxis implies that no other muscle relaxant should be administered without prior testing [185]. Usually, the muscle relaxant for which skin testing is negative should be used [79,102,186,187]. One should bear in mind, however, that even these recommendations do not guarantee absolute prevention of further adverse reactions [188], and that the safest approach is to avoid the drug class whenever possible.

As far as anaphylactic reactions to other drugs than anaesthetics are concerned, no data indicate the need for a particular procedure in the choice of anaesthetic agents. Obviously, the drug to which the patient is allergic must be avoided.

Back to Top | Article Outline

Latex allergy

The reported prevalence of latex allergy varies greatly depending upon the population studied and the methods used to detect sensitization. As is the case with all substances causing allergy, the greater the exposure in a population, the greater the number of sensitized individuals. The potentially life-threatening risk of anaphylactic shock during surgery in patients allergic to, or belonging to 'at-risk' groups for latex allergy, has recently been emphasized [165,189-191]. The initial signs suggesting allergy include pruritus, urticaria or contact angio-oedema. Conjunctivitis, rhinitis and asthma in subjects wearing gloves containing natural latex, or confined to an area in which the air is polluted by latex particles, has also been observed. Patients at risk must be routinely screened. High levels of latex-specific IgE antibodies can lead to anaphylactic shock during surgery if it is not performed in a latex-safe environment. 'At-risk' groups could be defined as follows [10,192]:

• Children, such as those with spina bifida, who have been operated on several times, and/or with prolonged use of indwelling urinary catheters, present a 40-50% risk of sensitization to latex. Controversy remains between authors who favour a positive relation between the number of operations and the frequency of latex allergy [193,194], and those who do not [175]

• These recommendations have recently been extended to patients with a history of multiple surgical procedures [10]. However, this also remains subject to controversy. In a recent study, we could not detect any increase in sensitization in spinal cord-injured adult patients [177]. This is also the case for chronic renal failure patients having a high degree of latex exposure [176]

• Healthcare workers who wear latex gloves or work in areas having a high concentration of latex particles, such as operating rooms. The risk of sensitization increases with increased exposure. The prevalence of sensitivity is 10%, and can reach 15.8% in anaesthetic staff [96]. Dental school students also present a particular risk, and sensitization increased from 0 to 10% in first- and fourth-year students, respectively [195]

• Other individuals with occupational exposure such as rubber industry workers [196]

• Patients allergic to several fruit (avocado, kiwi, banana, fig, chestnut, hazelnut, sweet pepper, melon, pineapple, papaya) due to cross-allergy with latex [197]

• Individuals with severe hand dermatitis who wear latex gloves. It has been suggested that dermatitis disrupts skin integrity and facilitates absorption of latex allergen

• Patients with a history of hay fever, rhinitis, asthma or eczema (atopy) are considered as being at risk in some recommendations [10], but not in others [11]. A significant number of atopic patients are reported in several series concerning latex sensitization [45,96,198,199], with an increased risk for latex allergy of 36%, compared with 9.4% in non-atopic patients [45]. In addition, atopic patients with asthma or allergic rhinitis to grass or weed pollens could have a cross-sensitivity to latex [200]. However, in the absence of well-defined positive and negative predictive values of systematic screening for latex sensitization in atopic patients before anaesthesia, this has not been recommended as standard clinical practice in France [11].

Back to Top | Article Outline

Investigation of an allergic reaction

Every patient who experiences an anaphylactoid reaction should benefit from immediate and delayed investigations to confirm an eventual IgE-mediated allergic reaction, to identify the responsible drug and to detect possible cross-reactivity in cases of anaphylaxis to a neuromuscular blocking agent [11]. The anaesthetist administering the drugs associated with the suspected anaphylactic reaction must be responsible for ensuring that these tests are performed and interpreted adequately. The investigation should be conducted in concert with an allergologist or a clinical immunologist. However, the anaesthetist remains responsible for providing further advice to the patient, informing the patient's primary care physician and recording all pertinent data in the patient medical record.

A detailed clinical history remains the single most important source of information when working up a prior allergic reaction. All drugs given before and during the anaesthesia, as well as their timing in relation to the reaction, must be noted. Diagnosis of most drug allergies is, in fact, presumptive and based on a temporal relation with the injection of the incriminated drug. After patient recovery, a detailed history including concurrent morbidity, previous anaesthetic history and any known allergies should be taken. The diagnostic strategy for a suspected anaphylactic reaction is based on laboratory tests, on samples taken during and shortly after the reaction, and on tests carried out days to weeks later. Early tests are essentially designed to determine whether an immunological mechanism is involved. Delayed testing attempts to identify the responsible drug. Whenever possible, confirmation of the incriminated allergen should be based on immunological assessment using more than one test.

Back to Top | Article Outline

Intraoperative testing

Tryptase. Tryptase is released from activated mast cells but not from basophils. Although elevated tryptase levels can be observed in different situations [201], an elevated serum tryptase concentration >25 μg L−1 is strongly in favour of an anaphylactic mechanism [11]. However, a negative test does not completely rule out anaphylaxis. Tryptase concentration should be determined approximately 1 h after the start of the reaction. Tryptase, whose half-life appears to be longer than that of histamine, can still be detected for 1-6 h or more after the onset of anaphylaxis [14,88,112,202]. Moreover, the potential interest and medico-legal value of mast cell tryptase measurement, even at autopsy, has been previously emphasized [88,203].

Histamine. Early increased plasma histamine and increased urinary methylhistamine concentrations may help to confirm the reality of in vivo histamine release [14-16,204]. A conference of European experts rigorously examined the most appropriate techniques for assaying histamine [205]. Histamine should be assayed within the first hour of a suspected anaphylactic reaction, and in mild cases, only early measurements may be increased [206]. Histamine assay should be avoided during pregnancy (particularly near term) and in patients receiving high doses of heparin because of a high rate of false-negativity [11,206,207]. Urinary methylhistamine assays are no longer recommended in view of their low sensitivity in comparison with tryptase and histamine assays.

Specific IgE assay. Radioimmunoassay for the detection of drug-reactive IgE antibody may provide important information for identification of the causative agent of anaphylaxis [13]. Although classically performed several weeks after the reaction, they can be carried out on blood drawn at the time of the reaction. As a result, the presence of specific IgE against the suspected drug at the time of the reaction can be substantiated [15]. Satisfactory correlation with subsequent immunological investigation has been reported when neuromuscular blocking agents are incriminated [15]. They can also help to confirm the diagnosis by identifying the responsible drug in patients in whom skin tests could either not been performed or were negative. These assays test for specific circulating IgE based on the assumption that they reflect IgE bound to mast cells.

Baldo and Fisher initially demonstrated the presence of neuromuscular blocking agent-specific IgE in serum [24] using muscle relaxant coupled to epoxy-Sepharose. Specific IgE adsorbed to the solid phase was detected using radiolabelled anti-IgE. Inhibition of IgE binding was obtained by preincubation of the sera with either soluble muscle relaxants or structurally related compounds. They concluded that the quaternary and tertiary ammonium ions were involved in the allergenic site. This explained the cross-reactivity between different muscle relaxants observed by skin testing, in vitro leukocyte histamine release and serum IgE-RIA [185,208]. The value of radioallergosorbent tests (RAST) for IgE antibodies to muscle relaxants and thiopental is well-established [209]. Although the sensitivity of the CAP-RAST® assay (Pharmacia and Upjohn) is limited (succinylcholine 66%, alcuronium 40%), several teams have improved the sensitivity of specific serum IgE detection up to 90-97% by coupling an analogue of choline to Sepharose (SAQ) [210,211], or p-aminophenylphosphoryl-choline on agarose beads (PAPPC) [211,212]. Recently, specific IgE detection based on morphine in solid-phase form has been proposed [213]. Placing the tested serum in the presence of the offending molecule in its soluble form controls inhibition of specific IgE binding [211]. The concordance rate with skin tests is good (about 83%) in most cases [214,215]. However, a limit to the generalized use of these assays for neuromuscular blocking agents is that, due to the preparation of the materials required for the test, they are usually only possible in specialized laboratories.

Specific IgE against thiopental, morphine, phenoperidine and propofol have also been detected in serum of sensitized patients, using IgE-RIA [31,32]. Two different allergenic determinants have been identified on opposite sides of the thiopental molecule. One of these determinants involves the ring nitrogens in the pyrimidine nucleus and could be responsible for in vitro cross-reactions with sera from patients allergic to muscle relaxants [31,117]. Recently, the presence of hydrophobic IgE reacting non-specifically with propofol has been reported [216]. This renders the interpretation of specific IgE assays to propofol difficult. In some patients, simultaneous presence of anti-quaternary ammonium IgE was observed. This could be a risk factor for an adverse allergic reaction to propofol and may explain the potentiating effect of the association between propofol and muscle relaxants on in vitro leukocyte histamine release performed in patients who reacted against both drugs [17]. With respect to latex, a radioallergosorbent test is available but is less sensitive than the skin prick test, detecting antibodies in only 50-70% of cases [217].

These factors have recently led to limiting the recommended indications for specific IgE assays to the diagnosis of anaphylaxis to neuromuscular blocking agents, thiopental and latex [11].

Back to Top | Article Outline

Postoperative testing

Skin testing. Intradermal skin or prick tests are usually carried out 6 weeks after a reaction, but may remain positive for years later [218-220]. Ideally, testing should be carried out by a professional experienced in performing and interpreting tests with anaesthetic agents [7,11]. Treatments such as antihistamines, known to decrease cutaneous reactivity, should be interrupted. Prick tests and intradermal reactions with dilutions of commercially available drug preparations are advised [25,221-223]. Standardized procedures and dilutions must be precisely defined for each agent tested, to avoid false-positive results due to direct histamine releasing properties. This could be the case for known histamine-releasing compounds (such as mivacurium, atracurium, tubocurarine and morphine). As such, these should be tested with more dilute solutions [26,185,222-224]. Control tests using saline (negative control) and codeine (positive control) must accompany skin tests to determine whether the skin is apt to release histamine and react to it. Although a certain degree of controversy remains about the maximal concentrations to be used [225], detailed recommendations for skin and intradermal test dilutions of anaesthetic drugs have recently been proposed by the French Society of Anaesthesia (SFAR, Société Française d'Anesthésie et de Réanimation) (Table 2)[11].

Table 2

Table 2

Any drug administered during the perioperative period should be considered as a potential cause. In addition, because of the frequent but not systematic cross-reactivity observed with muscle relaxants, every available neuromuscular blocking agent should be tested. This should help prevent future adverse reactions and provide documented advice for future administration of anaesthesia. Moreover, any new muscle relaxant should be routinely tested in patients known to be allergic to these agents to detect possible cross-reactivity [26,28,185].

The sensitivity of skin tests for muscle relaxants is approximately 94-97% [97,208]. However, sensitivity for other substances varies. It is good for synthetic gelatins, but poor for barbiturates, opioids and benzodiazepines [13,71,221]. There has been some controversy concerning the advantages of either prick or intradermal testing. Studies comparing both techniques show little differences between them [70,223]. However, reliability over time concerning prick testing has not been assessed [71], and the reliability of prick tests alone in the individual patient has been questioned by some [226]. Consequently, prick testing is advised for the diagnosis of the muscle relaxant responsible for an anaphylactic reaction, but intradermal testing should be preferred when investigating cross-reaction. In this case, dilutions should be increased to 10−1 to test most aminosteroid muscle relaxants [11]. Latex sensitization must be investigated by prick tests using two different commercial extracts, and in particular the recently standardized latex commercial extract (Stallergenes®) [227].

Other biological tests. Specific IgE radioimmunoassays for the detection of drug-reactive IgE antibody can be performed postoperatively if no blood was drawn at the time of the reaction [220], or when IgE assay is negative due to consumption of drug-specific antibodies during the anaphylactic reaction. However, specific IgE assay performed on blood drawn at the time of the reaction or (when available) prior to the reaction is preferable [15].

Several other tests have been proposed to allow for indirect detection of specific IgE to anaesthetic drugs. The Leukocyte Histamine Release test is reliable for muscle relaxants [228]. Its sensitivity is about 71% [210]. When combined with the simultaneous use of skin tests, and IgE-RIA, it allows for detection in the majority of cases [97]. However, it is quite expensive, time consuming, sometimes considered as a research tool [13], and not recommended in routine practice. Nevertheless, it could be useful when specific IgE assays are not available or when cross-reactivity among muscle relaxants in view of future anaesthesia in sensitized patients is investigated.

The study of human basophil activation by detection of altered plasma membrane molecule expression using flow cytometry has also been proposed [229-231]. These tests are based on the changes of membrane molecules such as CD 63 resulting from basophil activation in the presence of a suspected allergen. Its sensitivity in the diagnosis of muscle relaxant allergy is estimated at 64% and its specificity at 93% [230]. Their potential interest in the diagnosis of anaphylactic reactions to neuromuscular blockers requires further evaluation.

Reports concerning the monitoring of serotonin [232], eosinophil cationic protein [233] or LTC4 [234] release have also been published. However, these assays cannot be recommended in routine clinical practice at the present time.

Challenge tests. Indications for these tests are limited. They are restricted to local anaesthetics and latex [11]. They should only be performed in case of negative skin tests. Local anaesthetics can be tested by subcutaneously injecting 0.5-1.0 mL undiluted anaesthetic solution (without epinephrine). The test is considered negative if no adverse reaction occurs within 30 min after injection [125].

Wearing a latex glove on one hand compared with a vinyl glove on the other hand for 15 min can perform a latex glove provocation test [235]. The test is considered negative in the absence of any local symptoms during the 30 min following the glove-wearing period.

Back to Top | Article Outline

Investigation strategy prior to anaesthesia

In the absence of the established predictive value of tests for the occurrence of peroperative anaphylactic reactions [13,91,93,95], there is no demonstrated evidence for systematic preoperative screening in the general population at this time. Similarly, there is no evidence for the need of investigating sensitization against anaesthetic drugs in patients who are either atopic or sensitized to substances they would not be exposed to during anaesthesia.

Whenever possible, preanaesthetic assessment should be carried out in high-risk patients to detect sensitization to anaesthetic agents or latex. In spite of their satisfactory sensitivity, skin tests should be combined with an IgE assay if available [13]. The anaesthetic protocol for the patient depends on the results of this assessment. However, it should be kept in mind that skin tests performed belatedly after an adverse reaction during anaesthesia could be falsely negative. This is due to a possible spontaneous decrease of specific IgE concentration with time. It is always preferable that any investigation be carried out 6 weeks after the adverse reaction.

Consequently, an allergologic work-up is indicated in the following:

• Patients presenting a documented allergy to an anaesthetic drug or latex. The results of the initial investigations must be taken into account. When muscle relaxants are concerned, recent muscle relaxants should be tested before renewed anaesthesia

• Patients having experienced an unexplained reaction during a previous general anaesthesia, including severe hypotension, bronchospasm or oedema during recovery. It is conceivable that the reaction might have been related to sensitivity to an anaesthetic agent or latex. The list of all injected substances will help guide the allergologist through his assessment. If the anaesthetic protocol is unavailable, the substances that are most often incriminated in epidemiological studies should be tested (i.e. muscle relaxants and latex: skin tests, eventually specific IgE assays)

• Patients who allege an allergy to local anaesthetics, when local anaesthesia is scheduled. The local anaesthetic used at the time of the reaction, otherwise the most commonly reported local anaesthetics (i.e. lidocaine, mepivacaine and bupivacaine) should be tested. If an allergy to local anaesthetics is suspected, but skin tests are negative, progressive challenge testing may be indicated, according to the protocol described by Fisher and Bowey [125]

• Patients belonging to a high-risk group for sensitization to latex (children subjected to multiple operations, those with spina bifida, patients having experienced clinical symptoms of latex allergy in any circumstances, patients allergic to avocado, kiwi, banana, fig, chestnut, hazelnut, sweet pepper, melon, pineapple and papaya) (prick test ± specific IgE assays) [11,175,236,237].

In the case of emergency surgery, the anaesthetic technique used should be based on patient history (whenever possible):

• In case of unexplained reaction during previous general anaesthesia, regional block or general anaesthesia without muscle relaxant in a latex-safe environment is advisable

• In case of allergy to a local anaesthetic, general anaesthesia should be preferred. If regional block is still required, a challenge test must be performed and proved negative

• In case of known allergy to a muscle relaxant, all such drugs must be all avoided

• In case of a high risk of latex sensitization, surgery should be performed in a latex-safe environment.

Back to Top | Article Outline

Prevention and treatment

Prevention

Primary prevention. Prevention of anaphylaxis has two major objectives. It should be aimed at preventing sensitization of a patient to a particular allergen, or aimed at preventing the occurrence of an anaphylactic reaction to a reintroduced allergen in a presensitized patient. In this regard, prevention of latex allergy in spina bifida patients by primary prevention, which consists in avoiding latex during medical and surgical care of these patients, is very effective [157]. Similarly, the wearing of powderless, low-latex-allergen gloves by healthcare workers has been proposed as a possible means to reduce the levels of latex aeroallergen in the operating room and the rate of sensitization to latex in healthcare workers [6]. On the other hand, in the wake of the relatively high rate of sensitization in the absence of any prior exposure, optimal prevention of sensitization to neuromuscular blocking agents, even if their administration were radically curtailed, is probably unattainable [99].

Secondary prevention. Avoidance of causal agent Prevention of anaphylactic reactions relies mainly on accurate documentation of previous reactions and the avoidance of the incriminated drug. Therefore, during the preanaesthetic consultation, a detailed history should be taken, with special emphasis on atopy, drug allergy, allergy to latex and to tropical fruit. The use of a specific questionnaire is particularly helpful (Table 3)[11,164,192].

Table 3

Table 3

Latex-sensitive patients should be managed by complete avoidance of potential latex exposure [10,11]. This is most easily achieved if a comprehensive institutional policy exists. Patient care must be carefully co-ordinated among all professionals, including pre- and postoperative nursing teams and theatre staff. Whenever possible, the patient should be scheduled for elective surgery as the first case of the day to reduce patient exposure to aerosolized latex particles. Warnings identifying a risk for latex allergy should be posted inside and outside the operating room and in perioperative care areas, and the patient should wear a medical alert bracelet or necklace. A checklist of recommendations should accompany the patient throughout his/her hospital stay (Table 4). In addition, a list of readily available non-latex product alternatives should be established in collaboration with the facility's central supply area service and should be prominently displayed in patient care locations.

Table 4

Table 4

Back to Top | Article Outline

Pharmacological prophylaxis

Steroids and antihistamines. Pretreatment with corticosteroids or histamine-receptor antagonists, by either H1- or H1- and H2-receptor antagonists remains controversial. No evidence of beneficial effects of prophylactic administration of corticosteroids in anaesthesia has been shown at this time [158]. Pretreatment with H1- and H2-receptor antagonists reduces histamine-mediated adverse effects in various studies [238]. Antihistamine administration was effective in reducing the incidence of opioid-induced anaphylactoid reaction [239], and the adverse effects of non-immune histamine release following muscle relaxant [240,241] or vancomycin [140] administration. H1- and H2-receptor antagonist administration combined with widespread immunologic screening was reported to have beneficial effects on the incidence and severity of chymopapain-induced adverse reactions [242]. It has also been shown that H1- and H2-receptor antagonists have a beneficial effect in the prophylaxis of anaphylactoid reactions provoked by urea-linked gelatin solutions used as volume expanders [239], as well as in a prospective study conducted in patients undergoing standard general anaesthesia [243]. In fact, these beneficial effects have mainly been obtained during clinical manifestations associated with non-immunemediated histamine release.

Moreover, histamine detected during alarming immune-mediated reactions is merely a marker of co-release of more dangerous mediators. In addition, such a prophylactic approach has been found to be ineffective [244,245], or even, in some cases, deleterious [246,247]. Many authors consider that pretreatment with corticosteroids or antihistamines, or both, do not provide for a reliable prevention of immune-mediated reaction [10,42,248,249]. Nevertheless, even in the absence of any well-documented studies concerning anaphylaxis, some authors propose pretreatment with H1 or H1 and H2 antagonists as useful in the management of the patient with a history of anaphylaxis or at risk of non-immune histamine release [42,172,226,238]. In France, the use of these associations remains a matter of controversy. When prescribed, preventive treatment is usually limited to H1-receptor antagonists. However, proven anaphylactic reactions even in the wake of preoperative H1-H2-receptor antagonists and steroids have been documented in epidemiological surveys [29,146].

Monovalent hapten inhibition. Monovalent hapten inhibition with hapten dextran has been shown to significantly reduce but not completely abolish adverse reactions to dextran [250-253]. The use of monovalent haptens, which can occupy antibody sites without bridging specific IgE fixed on sensitized cells, has also been proposed for muscle relaxants. In this respect, any molecule presenting a quaternary ammonium ion could be considered as a potential monovalent hapten. Choline and tiemonium were initially used. Unfortunately, clinical tolerance of the highest doses was poor. As a result, the concentrations obtained were too low to be effective [254,255]. Recently, Moneret-Vautrin and colleagues demonstrated inhibition of skin mast-cell reactivity to muscle relaxants by mixing them with the monovalent haptens cytidylcholine and ethamsylate [256]. Furthermore, they obtained an inhibition of leukocyte histamine release for up to 3 h following the infusion of these monovalent haptens in patients allergic to muscle relaxants. Morphine, with its high affinity to reactive muscle relaxant antibodies, has also been proposed as a possible preventive hapten [13,226]. However, possible prevention of muscle relaxant anaphylaxis by monovalent haptens cannot be recommended in standard clinical practice [11].

Back to Top | Article Outline

Treatment

There is a wide array in reaction severity and in the efficacy of response to treatment. In addition, no controlled trials of treatment in humans are available. As a result, the ultimate judgement with regards to a particular clinical procedure or treatment scheme must be made by the clinician in light of the clinical presentation and available diagnostic and treatment options. Treatment of anaphylaxis is aimed at interrupting contact with the responsible antigen, modulating the effects of released mediators and inhibiting mediator production and release. It must be initiated as quickly as possible, and relies on widely admitted principles [7,11,164,172,226,248,257,258].

Non-specific measures. Administration of the suspected antigen must be interrupted, and the surgical procedure should be interrupted unless otherwise impossible.

Maintenance of airway patency is imperative and early endotracheal intubation should be considered because of a possible rapid onset of angio-oedema. Oxygen 100% should be administered. Large-bore i.v. access should be available, electrocardiograph and blood pressure monitoring must be started if not already performed, and the patient must lay flat with their lower limb elevated. These measures must be applied in all cases. They are usually sufficient in case of mild Grade I anaphylactoid reaction.

Specific treatment Anaphylactoid reaction of Grades II and III severity. Epinephrine is the drug of choice [259]. It opposes the deleterious systemic adverse effects of released mediators, through its vasoconstricting (α-mediated), positive inotropic (β1-mediated) and bronchodilating (β2-mediated) properties. It also reduces mast cell and basophil mediator release. Ventricular dysrhythmias have been reported in patients with pre-existing heart disease or in those receiving halogenated hydrocarbons [171]. However, this should not preclude administration of epinephrine, but electrocardiographic monitoring is indicated.

There are no data favouring one route of administration over another. Subcutaneous or intramuscular administration at a dose of 0.5-1.0 mg (10 μg kg−1 in children) repeated every 10 min [260], or even inhaled administration is possible [261-264].

When an i.v. route is available, titrated bolus administration according to arterial pressure and pulse is advised (10-20 μg in Grade II reactions, 100-200 μg in Grade III reactions) [7,11,265,266]. Administration should be renewed every 1-2 min until the clinical response is considered satisfactory (i.e. there is a measurable improvement in blood pressure, airway resistance and stabilization or regression of angio-oedema) [172]. Doses must be increased rapidly in case of inefficacy. Continuous infusion may be required in some cases (0.05-0.1 μg kg−1 min−1, titrated as needed).

Central venous and pulmonary artery catheterization for optimal guidance of inotropes and fluid volume administration should be considered in cases refractory to standard therapy. Prolonged monitoring in the intensive care unit is required because of the risk of recurrent reactions. Adjunction of anti-histamines and administration of H2-blocking drugs has also been proposed in some guidelines [258].

Intravascular volume expansion must be associated with vasoactive amines. Fluid infusion should be initiated immediately, while preparing epinephrine for injection. Rapid infusion of crystalloids (10-25 mL kg−1) over 20 min, repeated if necessary must be performed. Colloid infusion, avoiding any potentially incriminated solution, should be started when the volume of crystalloids infused >30 mL kg−1.

Bronchospasm is usually reversible with epinephrine. However, in case of persistent bronchospasm, or in the absence of arterial hypotension, inhaled β2-agonists (salbutamol) is advised. In case of refractory bronchospasm or immediate increased severity, i.v. administration of a bolus dose of 100-200 μg, followed by continuous infusion at 5-25 μg min−1 should be considered. Intravenous infusion can also be performed in non-intubated patients when appropriate inhalation chambers are unavailable.

Norepinephrine may be indicated in conditions where low peripheral perfusion pressure predisposes to intrapulmonary shunting (started at a 4-8 μg min−1, titrated as needed), or in case of persistent vasodilatation in the absence of bronchospasm [172]. Dobutamine can be used in case of pulmonary oedema, a cardiac assist device may be necessary if cardiac failure persists [172,267]. Phosphodiesterase inhibitors and PGE1 may be used in case of severe pulmonary hypertension [268].

In case of sympathetic blockade produced by either β-adrenoreceptor-blocking drugs or regional anaesthesia, symptoms are usually refractory to treatment. Doses of epinephrine should be increased (up to ≥10 mg); high-dose dopamine or other adrenoreceptor agonists may be required. Atropine (1-2 mg i.v.), as well as glucagon (initial dose 1-5 mg, followed by 1.0-2.5 mg h−1 infusion) may be added [269-271].

During pregnancy, hypotension must be initially treated by i.v. ephedrine injection; a 10 mg bolus dose repeated every 1 or 2 min (with cumulative doses up to 7 mg kg−1). Epinephrine administration should be started in case of inefficacy.

Anaphylactoid reaction of Grade IV severity - cardiac arrest. External cardiac massage must be instituted immediately; associated with a 1 mg bolus of epinephrine i.v. repeated every 1-2 min and rapidly increased to 5 mg as of the third injection. Cumulative doses could reach ≥50 mg. This must be associated with recommended practice guidelines concerning management of patient presenting with cardiac arrest.

Secondary therapy. Corticosteroids (hydrocortisone 200 mg i.v. every 6 h) can be administered to prevent delayed manifestations of anaphylaxis [11,272].

Back to Top | Article Outline

Conclusion

Anaphylaxis continues to be a significant adverse event during anaesthesia and is probably under diagnosed. Substances other than anaesthetic agents may cause it. Treatment is aimed at interrupting contact with the responsible antigen, modulating the effects of the released mediators, and inhibiting mediator production and release. It should be initiated immediately with a rapid administration of epinephrine. As for all rare events, detailed diagnostic and therapeutic protocols, as well as emergency drugs, should be available in operating rooms, and management training on the anaesthesia simulator is advised.

Because no premedication can effectively prevent an allergic reaction, it is the anaesthetist's responsibility to ensure that any suspected anaphylactic reaction be thoroughly investigated using combined per- and postoperative testing. In addition, systematic inquiries aimed at identifying patients belonging to an at-risk group must be performed before any anaesthesia. Patients must be fully informed of investigation results and advised to provide a detailed report before any future anaesthesia. The wearing of a warning bracelet or possession of a warning card is strongly indicated.

In view of the constantly evolving anaesthesiological practices and of the relative complexity of allergy investigation, an active policy to identify patients at risk and to provide any necessary support from expert advice to anaesthetists and allergologists through the constitution of allergo-anaesthesia centres should be promoted.

Back to Top | Article Outline

References

1. Jerums G, Whittingham S, Wilson P. Anaphylaxis to suxamethonium. A case report. Br J Anaesth 1967; 39: 73-77.
2. Fisher MM. Intradermal testing after severe histamine reactions to intravenous drugs used in anaesthesia. Anaesth Intensive Care 1976; 4: 97-104.
3. Sigiel M, Laxenaire MC, Moneret-Vautrin DA, et al. Trois cas de choc anaphylactique à la Célocurine. Anesth Analg 1975; 32: 447-462.
4. Vervloet D, Arnaud A, Vellieux P, Kaplanski S, Charpin J. Anaphylactic type of accidents due to myorelaxing agents during general anesthesia. Clinical and biological study. Nouv Presse Med 1977; 6: 725-728.
5. Gram LE, Hallas J, Andersen M. Pharmacovigilance based on prescription databases. Pharmacol Toxicol 2000; 86 (Suppl 1): 13-15.
6. Task Force on Allergic Reaction to Latex. American Academy of Allergy and Immunology. Committee Report. J Allergy Clin Immunol 1993; 92: 16-18.
7. Suspected Anaphylactic Reactions Associated with Anaesthesia, revd edn. London, UK: Association of Anaesthetists of Great Britain and Ireland and British Society of Allergy and Clinical Immunology, 1995.
8. Laurent J. Commission tripartite de consensus en allergologie. Rev Fr Allergol 1997; 37: 776-777.
9. American Academy of Dermatology's position paper on latex allergy. J Am Acad Dermatol 1998; 39: 98-106.
10. Task Force on Latex Sensitivity. Natural Rubber Latex Allergy: Considerations for Anesthesiologists. Park Ridge, II, USA: American Society of Anesthesiologists, 1999.
11. Prévention du risque allergique peranesthésique. Recommandations pour la pratique clinique. www.sfar.org, 2001. Ann Fr Anesth Reanim 2001; 20: 56-76.
12. Portier P, Richet C. De l'action anaphylactique de certains venins. CR Soc Biol 1902; 6: 170-172.
13. Fisher M, Baldo BA. Anaphylaxis during anaesthesia: current aspects of diagnosis and prevention. Eur J Anaesthesiol 1994; 11: 263-284.
14. Laroche D, Vergnaud MC, Sillard B, Soufarapis H, Bricard H. Biochemical markers of anaphylactoid reactions to drugs. Comparison of plasma histamine and tryptase. Anesthesiology 1991; 75: 945-949.
15. Laroche D, Lefrancois C, Gerard JL, et al. Early diagnosis of anaphylactic reactions to neuromuscular blocking drugs. Br J Anaesth 1992; 69: 611-614.
16. Laroche D, Dubois F, Lefrancois C, et al. Early biological markers of anaphylactoid reactions occurring during anesthesia. Ann Fr Anesth Reanim 1992; 11: 613-618.
17. Aimone-Gastin I, Gueant JL, Laxenaire MC, Monneret-Vautrin DA. Pathogenesis of allergic reactions to anaesthetic drugs. Int J Immunopathol Pharmacol 1997; 10: 193-196.
18. Falk K, Rotzschke O, Stevanovic S, Jung G, Rammensee HG. Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules. Nature 1991; 351: 290-296.
19. De Weck AL. Immunochemical particularities of anaphylactic reactions to compounds used in anesthesia. Ann Fr Anesth Reanim 1993; 12: 126-130.
20. Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature 1998; 392: 245-252.
21. Romagnoli P, Labhardt AM, Sinigaglia F. Selective interaction of Ni with an MHC-bound peptide. Embo J 1991; 10: 1303-1306.
22. Zanni MP, Pichler W. Allergic reactions to drugs. Functional involvement of T cells. ACI Int 1997; 9: 174-179.
23. Van den Broeke LT, Heffler LC, Tengvall-Linder M, et al. Direct Ni2+ antigen formation on cultured human dendritic cells. Immunology 1999; 96: 578-585.
24. Baldo BA, Fisher MM. Substituted ammonium ions as allergenic determinants in drug allergy. Nature 1983; 306: 262-264.
25. Birnbaum J, Vervloet D. Allergy to muscle relaxants. Clin Rev Allergy 1991; 9: 281-293.
26. Leynadier F, Dry J. Anaphylaxis to muscle-relaxant drugs: study of cross-reactivity by skin tests. Int Arch Allergy Appl Immunol 1991; 94: 349-353.
27. Vervloet D, Arnaud A, Vellieux P, Kaplanski S, Charpin J. Anaphylactic reactions to muscle relaxants under general anesthesia. J Allergy Clin Immunol 1979; 63: 348-353.
28. Fisher MM. Anaphylaxis to muscle relaxants: cross sensitivity between relaxants. Anaesth Intensive Care 1980; 8: 211-213.
29. Laxenaire MC. Epidémiologie des réactions anaphylactoïdes peranesthésiques. Quatrième enquête multicentrique (juillet 1994-décembre 1996). Ann Fr Anesth Reanim 1999; 18: 796-809.
30. Baldo BA, Harle DG. Drug allergenic determinants. In: Baldo BA. (ed.). Molecular Approaches to the Study of Allergens. Monographs in Allergy, Vol. 28. Basel, Switzerland: Karger, 1990: 11-51.
31. Baldo BA, Fisher MM, Harle DG. Allergy to thiopentone. Clin Rev Allergy 1991; 9: 295-308.
32. Fisher MM, Harle DG, Baldo BA. Anaphylactoid reactions to narcotic analgesics. Clin Rev Allergy 1991; 9: 309-318.
33. Alenius H, Turjanmaa K, Makinen-Kiljunen S, Reunala T, Palosuo T. IgE immune response to rubber proteins in adult patients with latex allergy. J Allergy Clin Immunol 1994; 93: 859-863.
34. Beezhold DH, Hickey VL, Slater JE, Sussman GL. Human IgE-binding epitopes of the latex allergen Hev b 5. J Allergy Clin Immunol 1999; 103: 1166-1172.
35. Slater JE, Paupore EJ, O'Hehir RE. Murine B-cell and T-cell epitopes of the allergen Hev b 5 from natural rubber latex. Mol Immunol 1999; 36: 135-143.
36. Kurup VP, Yeang HY, Sussman GL, et al. Detection of immunoglobulin antibodies in the sera of patients using purified latex allergens. Clin Exp Allergy 2000; 30: 359-369.
37. Alenius H, Palosuo T, Kelly K, et al. IgE reactivity to 14-kD and 27-kD natural rubber proteins in latex-allergic children with spina bifida and other congenital anomalies. Int Arch Allergy Immunol 1993; 102: 61-66.
38. Alenius H, Kurup V, Kelly K, et al. Latex allergy: frequent occurrence of IgE antibodies to a cluster of 11 latex proteins in patients with spina bifida and histories of anaphylaxis. J Lab Clin Med 1994; 123: 712-720.
39. Ylitalo L, Alenius H, Turjanmaa K, Palosuo T, Reunala T. IgE antibodies to prohevein, hevein, and rubber elongation factor in children with latex allergy. J Allergy Clin Immunol 1998; 102: 659-664.
40. Lenius H, Kalkkinen N, Lukka M, et al. Prohevein from the rubber tree (Hevea brasiliensis) is a major latex allergen. Clin Exp Allergy 1995; 25: 659-665.
41. Alenius H, Kalkkinen N, Yip E, et al. Significance of rubber elongation factor as a latex allergen. Int Arch Allergy Immunol 1996; 109: 362-368.
42. Moneret-Vautrin DA, Laxenaire MC. The risk of allergy related to general anaesthesia. Clin Exp Allergy 1993; 23: 629-633.
43. M'Raihi L, Charpin D, Pons A, Bongrand P, Vervloet D. Cross-reactivity between latex and banana. J Allergy Clin Immunol 1991; 87: 129-130.
44. Fernandez de Corres L, Moneo I, Munoz D, et al. Sensitization from chestnuts and bananas in patients with urticaria and anaphylaxis from contact with latex. Ann Allergy 1993; 70: 35-39.
45. Moneret-Vautrin DA, Beaudouin E, Widmer S, et al. Prospective study of risk factors in natural rubber latex hypersensitivity. J Allergy Clin Immunol 1993; 92: 668-677.
46. Kurup VP, Kelly T, Elms N, Kelly K, Fink J. Cross-reactivity of food allergens in latex allergy. Allergy Proc 1994; 15: 211-216.
47. Blanco C, Carrillo T, Castillo R, Quiralte J, Cuevas M. Latex allergy: clinical features and cross-reactivity with fruits. Ann Allergy 1994; 73: 309-314.
48. Lavaud F, Prevost A, Cossart C, et al. Allergy to latex, avocado pear, and banana: evidence for a 30 kd antigen in immunoblotting. J Allergy Clin Immunol 1995; 95: 557-564.
49. Delbourg MF, Moneret-Vautrin DA, Guilloux L, Ville G. Hypersensitivity to latex and Ficus benjamina allergens. Ann Allergy Asthma Immunol 1995; 75: 496-500.
50. Antico A. Oral allergy syndrome induced by chestnut (Castanea sativa). Ann Allergy Asthma Immunol 1996; 76: 37-40.
51. Diez-Gomez ML, Quirce S, Aragoneses E, Cuevas M. Asthma caused by Ficus benjamina latex: evidence of cross-reactivity with fig fruit and papain. Ann Allergy Asthma Immunol 1998; 80: 24-30.
52. Chen Z, Posch A, Cremer R, Raulf-Heimsoth M, Baur X. Identification of hevein (Hev b 6.02) in Hevea latex as a major cross-reacting allergen with avocado fruit in patients with latex allergy. J Allergy Clin Immunol 1998; 102: 476-481.
53. Gallo R, Roncarolo D, Mistrello G. Cross-reactivity between latex and sweet pepper due to prohevein. Allergy 1998; 53: 1007-1008.
54. Mikkola JH, Alenius H, Kalkkinen N, et al. Hevein-like protein domains as a possible cause for allergen cross-reactivity between latex and banana. J Allergy Clin Immunol 1998; 102: 1005-1012.
55. Posch A, Wheeler CH, Chen Z, et al. Class I endochitinase containing a hevein domain is the causative allergen in latex-associated avocado allergy. Clin Exp Allergy 1999; 29: 667-672.
56. Diez-Gomez ML, Quirce S, Cuevas M, et al. Fruit-pollen-latex cross-reactivity: implication of profilin (Bet v 2). Allergy 1999; 54: 951-961.
57. Seppala U, Palosuo T, Kalkkinen N, et al. IgE reactivity to patatin-like latex allergen, Hev b 7, and to patatin of potato tuber, Sol t 1, in adults and children allergic to natural rubber latex. Allergy 2000; 55: 266-273.
58. Anliker MD, Reindl J, Vieths S, Wuthrich B. Allergy caused by ingestion of persimmon (Diospyros kaki): detection of specific IgE and cross-reactivity to profilin and carbohydrate determinants. J Allergy Clin Immunol 2001; 107: 718-723.
59. Paton WDM. Histamine release by compounds of simple chemical structure. Pharmacological Review 1957; 9: 269-328.
60. Séminaire 'Allergie et anesthésie', Nancy, France. Ann Anesth Fr 1975.
61. Watkins J, Clarke R. Report of symposium: adverse reaction to intravenous agent. Br J Anaesth 1978; 50: 1159-1164.
62. Ahnefeld FW, Doenicke A, Lorenz W. Histamine and Antihistamines in Anaesthesia and Surgery, Munich, 1981; Klin Wochenschr 1982; 60: 871-1062.
63. Séminaire 'Diagnostic d'un accident anaphylactoïde peranesthésique', Nancy, France. Ann Fr Anesth Reanim 1982.
64. Séminaire 'Prévention des risques anaphylactoïdes peranesthésiques', Nancy, France. Ann Fr Anesth Reanim 1985.
65. Séminaire 'd'allergo-anesthésie', Nancy, France. Ann Fr Anesth Reanim 1989.
66. Séminaire 'New trends in anaphylactoid risk in anaesthesia', Nancy, France. Ann Fr Anesth Reanim, 1992.
67. Lorenz W, Doenicke A, Feifel G, et al. Histamine release in man by propanidid (Epontol), gelatin (Haemaccel), histalog, pentagastrin and insulin. Naunyn Schmiedebergs Arch Pharmacol 1970; 266: 396-397.
68. Lorenz W, Doenicke A, Schoning B, et al. Definition and classification of the histamine-release response to drugs in anaesthesia and surgery: studies in the conscious human subject. Klin Wochenschr 1982; 60: 896-913.
69. Galletly DC, Treuren BC. Anaphylactoid reactions during anaesthesia. Seven years' experience of intradermal testing. Anaesthesia 1985; 40: 329-333.
70. Leynadier F, Sansarricq M, Didier JM, Dry J. Prick tests in the diagnosis of anaphylaxis to general anaesthetics. Br J Anaesth 1987; 59: 683-689.
71. Fisher M. Intradermal testing after anaphylactoid reaction to anaesthetic drugs: practical aspects of performance and interpretation. Anaesth Intensive Care 1984; 12: 115-120.
72. Assem ESK. Anaphylactoid reactions to neuromuscular blockers: major role of IgE antibodies and possible contribution of IgE-independent mechanisms. In: Assem E-SK (ed.). Allergic Reactions to Anaesthetics: Clinical and Basic Aspects. Monogr Allergy, Vol. 30. Basel, Switzerland: Karger, 1992: 24-53.
73. Laxenaire MC, Moneret-Vautrin DA, Boileau S, Moeller R. Adverse reactions to intravenous agents in anaesthesia in France. Klin Wochenschr 1982; 60: 1006-1009.
74. Laxenaire MC. Drugs and other agents involved in anaphylactic shock occurring during anaesthesia. A French multicenter epidemiological inquiry. Ann Fr Anesth Reanim 1993; 12: 91-96.
75. Laxenaire MC, Charpentier C, Feldman L. Anaphylactoid reactions to colloid plasma substitutes: incidence, risk factors, mechanisms. A French multicenter prospective study. Ann Fr Anesth Reanim 1994; 13: 301-310.
76. Laxenaire MC. Substances responsible for peranesthetic anaphylactic shock. A third French multicenter study (1992-1994). Ann Fr Anesth Reanim 1996; 15: 1211-1218.
77. Fisher MM, More DG. The epidemiology and clinical features of anaphylactic reactions in anaesthesia. Anaesth Intensive Care 1981; 9: 226-234.
78. Fisher MM, Baldo BA. The incidence and clinical features of anaphylactic reactions during anesthesia in Australia. Ann Fr Anesth Reanim 1993; 12: 97-104.
79. Fisher MM. Anaphylactoid reactions during anaesthesia. In: Prys-Roberts C (ed.). International Practice of Anaesthesia, Vol. 1. Oxford, UK: Butterworth-Heinemann, 1996: 1-13.
80. Clarke RS. Epidemiology of adverse reactions in anaesthesia in the United Kingdom. Klin Wochenschr 1982; 60: 1003-1005.
81. Watkins J. Adverse anaesthetic reactions. An update from a proposed national reporting and advisory service. Anaesthesia 1985; 40: 797-800.
82. Watkins J. Second report from an anaesthetic reactions advisory service. Anaesthesia 1989; 44: 157-159.
83. Clarke RS, Watkins J. Drugs responsible for anaphylactoid reactions in anaesthesia in the United Kingdom. Ann Fr Anesth Reanim 1993; 12: 105-108.
84. Pepys J, Pepys EO, Baldo BA, Whitwam JG. Anaphylactic/anaphylactoid reactions to anaesthetic and associated agents. Skin prick tests in aetiological diagnosis. Anaesthesia 1994; 49: 470-475.
85. Sage D. Intradermal drug testing following anaphylactoid reactions during anaesthesia. Anaesth Intensive Care 1981; 9: 381-386.
86. Moscicki RA, Sockin SM, Corsello BF, Ostro MG, Bloch KJ. Anaphylaxis during induction of general anesthesia: subsequent evaluation and management. J Allergy Clin Immunol 1990; 86: 325-332.
87. Knowles SR, Weber E, Shear NH. Allergic reactions during general anesthesia (GA). J Allergy Clin Immunol 1996; 97: 344.
88. Fisher MM, Baldo BA. The diagnosis of fatal anaphylactic reactions during anaesthesia: employment of immunoassays for mast cell tryptase and drug-reactive IgE antibodies. Anaesth Intensive Care 1993; 21: 353-357.
89. Currie M, Webb RK, Williamson JA, Russell WJ, Mackay P. The Australian Incident Monitoring Study. Clinical anaphylaxis: an analysis of 2000 incident reports. Anaesth Intensive Care 1993; 21: 621-625.
90. Mitsuhata H, Matsumoto S, Hasegawa J. The epidemiology and clinical features of anaphylactic and anaphylactoid reactions in the perioperative period in Japan. Masui 1992; 41: 1664-1669.
91. Porri F, Lemiere C, Birnbaum J, et al. Prevalence of muscle relaxant sensitivity in a general population: implications for a preoperative screening. Clin Exp Allergy 1999; 29: 72-75.
92. Albrech C, Widmer S, Beaudoin E, Moneret-Vautrin DA, Laxenaire MC. Prospective study of sensitization to muscle relaxants. J Allergy Clin Immunol 1995; 95: 289.
93. Moneret-Vautrin DA, Renaudin JM, Kanny G, et al. Prospective study of the latent sensitization to muscle relaxants In: Dehling AK, Huerat-Lopez JG (eds). Progress in Allergy and Clinical Immunology, Vol. 4. Gottingen, Germany: Cancun, Hogrefe & Huber, 1997: 361-376.
94. Turjanmaa K, Reunala T. Incidence of positive prick test to rubber protein. Contact Dermatitis 1990; 23: 279.
95. Porri F, Lemiere C, Birnbaum J, et al. Prevalence of latex sensitization in subjects attending health screening: implications for a perioperative screening. Clin Exp Allergy 1997; 27: 413-417.
96. Konrad C, Fieber T, Gerber H, Schuepfer G, Muellner G. The prevalence of latex sensitivity among anesthesiology staff. Anesth Analg 1997; 84: 629-633.
97. Laxenaire MC, Moneret-Vautrin DA. Allergy and anaesthesia. Curr Opinion Anaesthesiol 1992; 5: 436-441.
98. Watkins J. Adverse reaction to neuromuscular blockers: frequency, investigation, and epidemiology. Acta Anaesthesiol Scand Suppl 1994; 102: 6-10.
99. Laxenaire M, Mertes PM. Groupe d'Etudes des Réactions Anaphylactoïdes Peranesthésiques. Anaphylaxis during anaesthesia. Results of a 2 year survey in France. Br J Anaesth 2001; 87: 549-558.
100. Baird MB, Futter M. Anaphylaxis to mivacurium. Anaesth Intensive Care 1996; 24: 486-488.
101. Yee R, Fernandez JA. Anaphylactic reaction to rocuronium bromide. Anaesth Intensive Care 1996; 24: 601-604.
102. Clendenen SR, Harper JV, Wharen RE Jr, Guarderas JC. Anaphylactic reaction after cisatracurium. Anesthesiology 1997; 87: 690-692.
103. Whittington T, Fisher MM. Anaphylactic and anaphylactoid reactions. B Clin Anaesthesiol 1998; 12: 301-323.
104. Barthelet Y, Ryckwaert Y, Plasse C, Bonnet-Royer MC, d'Athis F. Severe anaphylactic reactions to rocuronium bromide. Ann Fr Anesth Reanim 1999; 18: 896-900.
105. Duvaldestin P, Wigdorowicz C, Gabriel I. Anaphylactic shock to neuromuscular blocking agent: a familial history. Anesthesiology 1999; 90: 1211-1212.
106. Toh KW, Deacock SJ, Fawcett WJ. Severe anaphylactic reaction to cisatracurium. Anesth Analg 1999; 88: 462-464.
107. Matthey P, Wang P, Finegan BA, Donnelly M. Rocuronium anaphylaxis and multiple neuromuscular blocking drug sensitivities. Can J Anaesth 2000; 47: 890-893.
108. Donnelly T. Anaphylaxis to rocuronium. Br J Anaesth 2000; 84: 696.
109. Allen SJ, Gallagher A, Paxton LD. Anaphylaxis to rocuronium. Anaesthesia 2000; 55: 1223-1224.
110. Heier T, Guttormsen AB. Anaphylactic reactions during induction of anaesthesia using rocuronium for muscle relaxation: a report including 3 cases. Acta Anaesthesiol Scand 2000; 44: 775-781.
111. Neal SM, Manthri PR, Gadiyar V, Wildsmith JA. Histaminoid reactions associated with rocuronium. Br J Anaesth 2000; 84: 108-111.
112. Fisher MM, Baldo BA. Mast cell tryptase in anaesthetic anaphylactoid reactions. Br J Anaesth 1998; 80: 26-29.
113. Lorenz W, Doenicke A. Anaphylactoid reactions and histamine release by barbiturate induction agents: clinical relevance and pathomechanisms. Anesthesiology 1985; 1: 351-352.
114. Lilly JK, Hoy RH. Thiopental anaphylaxis and reagin involvement. Anesthesiology 1980; 53: 335-337.
115. Harle DG, Baldo BA, Smal MA, Wajon P, Fisher MM. Detection of thiopentone-reactive IgE antibodies following anaphylactoid reactions during anaesthesia. Clin Allergy 1986; 16: 493-498.
116. Fisher M, Ross J, Harle D, Baldo B. Anaphylaxis to thiopentone: an unusual outbreak in a single hospital. Anaesth Intensive Care 1989; 17: 361-365.
117. Moneret-Vautrin DA, Widmer S, Gueant JL, et al. Simultaneous anaphylaxis to thiopentone and a neuromuscular blocker: a study of two cases. Br J Anaesth 1990; 64: 743-745.
118. Harle D, Baldo B, Fisher M. The molecular basis of IgE antibody binding to thiopentone. Binding of IgE from thiopentone-allergic and non-allergic subjects. Molec Immunol 1990; 27: 853-858.
119. Baldo BA, Fisher MM. Diagnosis of IgE-dependent anaphylaxis to neuromuscular blocking drugs, thiopentone and opioids. Ann Fr Anesth Reanim 1993; 12: 173-181.
120. Laxenaire MC, Mata-Bermejo E, Moneret-Vautrin DA, Gueant JL. Life-threatening anaphylactoid reactions to propofol (Diprivan). Anesthesiology 1992; 77: 275-280.
121. Zucker-Pinchoff B, Rimanathan S. Anaphylactic reaction to epidural fentanyl. Anesthesiology 1989; 71: 599-601.
122. Zucker-Pinchoff B, Chandler MJ. Latex anaphylaxis masquerading as fentanyl anaphylaxis: retraction of a case report. Anesthesiology 1993; 79: 1152-1153.
123. Harle DG, Baldo BA, Coroneos NJ, Fisher MM. Anaphylaxis following administration of papaveretum. Case report: implication of IgE antibodies that react with morphine and codeine, and identification of an allergic determinant. Anesthesiology 1989; 71: 489-494.
124. Verrill P. Adverse reactions to local anaesthetics and vasoconstrictor drugs. Practitioner 1975; 214: 380-387.
125. Fisher MM, Bowey CJ. Alleged allergy to local anaesthetics. Anaesth Intensive Care 1997; 25: 611-614.
126. Burgess JO. Preventing adverse local anesthetic reactions: the use of the skin test. Spec Care Dentist 1987; 7: 135-136.
127. Klein CE, Gall H. Type IV allergy to amide-type local anesthetics. Contact Dermatitis 1991; 25: 45-48.
128. Cuesta-Herranz J, de las Heras M, Fernandez M, et al. Allergic reaction caused by local anesthetic agents belonging to the amide group. J Allergy Clin Immunol 1997; 99: 427-428.
129. Ismail K, Simpson PJ. Anaphylactic shock following intravenous administration of lignocaine. Acta Anaesthesiol Scand 1997; 41: 1071-1072.
130. Winton GB. Anesthesia for dermatologic surgery. J Dermatol Surg Oncol 1988; 14: 41-54.
131. Ruzicka T, Gerstmeier M, Przybilla B, Ring J. Allergy to local anesthetics: comparison of patch test with prick and intradermal test results. J Am Acad Dermatol 1987; 16: 1202-1208.
132. Canfield DW, Gage TW. A guideline to local anesthetic allergy testing. Anesth Prog 1987; 34: 157-163.
133. Fine PG, Dingman DL. Hypersensitivity dermatitis following suction-assisted lipectomy: a complication of local anesthetic. Ann Plast Surg 1988; 20: 573-575.
134. Simon RA. Adverse reactions to drug additives. J Allergy Clin Immunol 1984; 74: 623-630.
135. Schwartz HJ, Sher TH. Bisulfite sensitivity manifesting as allergy to local dental anesthesia. J Allergy Clin Immunol 1985; 75: 525-527.
136. Dooms-Goossens A, de Alam AG, Degreef H, Kochuyt A. Local anesthetic intolerance due to metabisulfite. Contact Dermatitis 1989; 20: 124-126.
137. Wessel F. Peri-anesthesia allergies to antibiotics. Allerg Immunol 1998; 30: 190-192.
138. Renz C, Lynch J, Thurn J, Moss J. Histamine release during rapid vancomycin administration. Inflamm Res 1998; 47 (Suppl 1): 69-70.
139. Renz CL, Laroche D, Thurn JD, et al. Tryptase levels are not increased during vancomycin-induced anaphylactoid reactions. Anesthesiology 1998; 89: 620-625.
140. Renz CL, Thurn JD, Finn HA, Lynch JP, Moss J. Antihistamine prophylaxis permits rapid vancomycin infusion. Crit Care Med 1999; 27: 1732-1737.
141. Keith PK, Dolovich J. Anaphylactic and anaphylactoid reactions in the perioperative period. Immunol Allergy Clin North Am 1992; 12: 671-690.
142. Sharath MD, Metzger WJ, Richerson HB, et al. Protamine-induced fatal anaphylaxis. Prevalence of antiprotamine immunoglobulin E antibody. J Thorac Cardiovasc Surg 1985; 90: 86-90.
143. Lakin JD, Blocker TJ, Strong DM, Yocum MW. Anaphylaxis to protamine sulfate mediated by a complement-dependent IgG antibody. J Allergy Clin Immunol 1978; 61: 102-107.
144. Weiss ME, Nyhan D, Peng ZK, et al. Association of protamine IgE and IgG antibodies with life-threatening reactions to intravenous protamine. N Engl J Med 1989; 320: 886-892.
145. Neidhart PP, Meier B, Polla BS, Schifferli JA, Morel DR. Fatal anaphylactoid response to protamine after percutaneous transluminal coronary angioplasty. Eur Heart J 1992; 13: 856-858.
146. Laxenaire MC, Dewachter P, Pecquet C. Allergic risk of aprotinin. Ann Fr Anesth Reanim 2000; 19: 96-104.
147. Schuler TM, Frosch PJ, Wahl DA. Allergie vom sofortyp. Anaphylaktishe reaktion and aprotinin. Münch med Wschr 1987; 129: 816-817.
148. Leskiw U, Levy JH. Antigenicity of protamine and aprotinin in cardiac surgery. In: Pifarre R (ed.). Blood Conservation with Aprotinin. Philadelphia, USA: Hanley & Belfus, 1995: 253-266.
149. Schulze K, Graeter T, Schaps D, Hausen B. Severe anaphylactic shock due to repeated application of aprotinin in patients following intrathoracic aortic replacement. Eur J Cardiothorac Surg 1993; 7: 495-496.
150. Nieto A, Estornell F, Mazon A, Reig C, Garcia-Ibarra F. Allergy to latex in spina bifida: a multivariate study of associated factors in 100 consecutive patients. J Allergy Clin Immunol 1996; 98: 501-507.
151. Niggemann B, Breiteneder H. Latex allergy in children. Int Arch Allergy Immunol 2000; 121: 98-107.
152. Beaudouin E, Prestat F, Schmitt M, et al. High risk of sensitization to latex in children with spina bifida. Eur J Pediatr Surg 1994; 4: 90-93.
153. Nieto A, Mazon A, Estornell F, Reig C, Garcia-Ibarra F. The search of latex sensitization in spina bifida: diagnostic approach. Clin Exp Allergy 2000; 30: 264-269.
154. Arellano R, Bradley J, Sussman G. Prevalence of latex sensitization among hospital physicians occupationally exposed to latex gloves. Anesthesiology 1992; 77: 905-908.
155. DuBuske L, Babahkin A, Cieslewicz G, Nolte H, Sheffer AL. Clinical assessment of latex allergy among hospital health care providers. Int Arch Allergy Immunol 1999; 118: 253-254.
156. Holzman RS. Clinical management of latex-allergic children. Anesth Analg 1997; 85: 529-533.
157. Cremet R, Kleine-Diepenbruck U, Hoppe A, Bläker F. Latex allergy in spina bifida patients by primary prophylaxis. Allergy 1998; 53: 709-711.
158. Ring J, Messmer K. Incidence and severity of anaphylactoid reactions to colloid volume substitutes. Lancet 1977; 1: 466-469.
159. Lorenz W, Doenicke A, Messmer K, et al. Histamine release in human subjects by modified gelatin (Haemaccel) and dextran: an explanation for anaphylactoid reactions observed under clinical conditions? Br J Anaesth 1976; 48: 151-165.
160. Kreimeier U, Christ F, Kraft D, et al. Anaphylaxis due to hydroxyethyl-starch-reactive antibodies. Lancet 1995; 346: 49-50.
161. McHugh GJ. Anaphylactoid reaction to pentastarch. Can J Anaesth 1998; 45: 270-272.
162. Kannan S, Milligan KR. Moderately severe anaphylactoid reaction to pentastarch (200/0.5) in a patient with acute severe asthma. Intensive Care Med 1999; 25: 220-222.
163. Dieterich HJ, Kraft D, Sirtl C, et al. Hydroxyethyl starch antibodies in humans: incidence and clinical relevance. Anesth Analg 1998; 86: 1123-1126.
164. Mertes PM, Laxenaire M. Anaphylaxis during general anaesthesia. Prevention and management. CNS Drugs 2000; 14: 115-133.
165. Leynadier F, Pecquet C, Dry J. Anaphylaxis to latex during surgery. Anaesthesia 1989; 44: 547-550.
166. Moneret-Vautrin DA, Laxenaire MC. Anaphylactic and anaphylactoid reactions. Clinical presentation. Clin Rev Allergy 1991; 9: 249-258.
167. Steiner DJ, Schwager RG. Epidemiology, diagnosis, precautions, and policies of intraoperative anaphylaxis to latex. J Am Coll Surg 1995; 180: 754-761.
168. Cardot E, Tillie-Leblond I, Jeannin P, et al. Anaphylactic reaction to local administration of rifamycin SV. J Allergy Clin Immunol 1995; 95: 1-7.
169. Laxenaire MC, Mouton C, Frederic A, Viry-Babel F, Bouchon Y. Anaphylactic shock after tourniquet removal in orthopedic surgery. Ann Fr Anesth Reanim 1996; 15: 179-184.
170. Stellato C, de Paulis A, Cirillo R, et al. Heterogeneity of human mast cells and basophils in response to muscle relaxants. Anesthesiology 1991; 74: 1078-1086.
171. Fisher MM. Clinical observations on the pathophysiology and treatment of anaphylactic cardiovascular collapse. Anaesth Intensive Care 1986; 14: 17-21.
172. Fisher M. Treatment of acute anaphylaxis. Br Med J 1995; 311: 731-733.
173. Youngman PR, Taylor KM, Wilson JD. Anaphylactoid reactions to neuromuscular blocking agents: a commonly undiagnosed condition? Lancet 1983; 2: 597-599.
174. Clergue F, Auroy Y, Pequignot F, et al. French survey of anesthesia in 1996. Anesthesiology 1999; 91: 1509-1520.
175. Ylitalo L, Turjanmaa K, Palosuo T, Reunala T. Natural rubber latex allergy in children who had not undergone surgery and children who had undergone multiple operations. J Allergy Clin Immunol 1997; 100: 606-612.
176. Kalpaklioglu AF, Aydin G. Prevalence of latex sensitivity among patients with chronic renal failure: a new risk group? Artif Organs 1999; 23: 139-142.
177. Mertes PM, Mouton C, Frémont S, et al. Latex hypersensitivity in spinal cord injured adult patients. Anaesth Intensive Care 2001; 4: 383-389.
178. Charpin D, Benzarti M, Hemon Y, et al. Atopy and anaphylactic reactions to suxamethonium. J Allergy Clin Immunol 1988; 82: 356-360.
179. Fisher M, Outhred A, Bowey C. Can clinical anaphylaxis to anaesthetic drugs be predicted from allergic history? Br J Anaesth 1987; 59: 690-692.
180. Guldager H, Sondergaard I, Jensen FM, Cold G. Basophil histamine release in asthma patients after in vitro provocation with Althesin and etomidate. Acta Anaesthesiol Scand 1985; 29: 352-353.
181. Akagi K, Townley RG. Spontaneous histamine release and histamine content in normal subjects and subjects with asthma. J Allergy Clin Immunol 1989; 83: 742-749.
182. Laxenaire M, Mata E, Guéant J, Moneret-Vautrin D, Haberer J. Basophil histamine release in atopic patients after in vitro provocation with thiopental, diprivan and chlormethiazole. Acta Anaesthesiol Scand 1991; 35: 706-710.
183. Naguib M, Samarkandi AH, Bakhamees HS, Magboul MA, el-Bakry AK. Histamine-release haemodynamic changes produced by rocuronium, vecuronium, mivacurium, atracurium and tubocuratine. Br J Anaesth 1995; 75: 588-592.
184. Laroche D, Bricard H, Laxenaire MC. Allergo-anesthesia consultation: not enough patients are tested after an anaphylactoid anesthetic incident. Ann Fr Anesth Reanim 1998; 17: 89-90.
185. Laxenaire MC, Gastin I, Moneret-Vautrin DA, Widmer S, Gucant JL. Cross-reactivity of rocuronium with other neuromuscular blocking agents. Eur J Anaesthesiol 1995; Suppl11: 55-64.
186. Leynadier F, Calinaux C, Dry J. Predictive value of intradermal tests using muscle-relaxing drugs. Ann Fr Anesth Reanim 1989; 8: 98-101.
187. Thacker MA, Davis FM. Subsequent general anaesthesia in patients with a history of previous anaphylactoid/anaphylactic reaction to muscle relaxant. Anaesth Intensive Care 1999; 27: 190-193.
188. Fisher MM, Merefield D, Baldo B. Failure to prevent an anaphylactic reaction to a second neuromuscular blocking drug during anaesthesia. Br J Anaesth 1999; 82: 770-773.
189. Slater JE. Rubber anaphylaxis. N Engl J Med 1989; 320: 1126-1130.
190. Ellsworth PI, Merguerian PA, Klein RB, Rozycki AA. Evaluation and risk factors of latex allergy in spina bifida patients: is it preventable? J Urol 1993; 150: 691-693.
191. Shenot P, Rivas DA, Kalman DD, Staas WE Jr, Chancellor MB. Latex allergy manifested in urological surgery and care of adult spinal cord injured patients. Arch Phys Med Rehabil 1994; 75: 1263-1265.
192. Bouaziz H, Laxenaire MC. Anaesthesia for the allergic patient. Curr Op Anaesth 1998; 11: 339-344.
193. Mazon A, Nieto A, Estornell F, Reig C, Garcia-Ibarra F. Factors that influence the presence of symptoms caused by latex allergy in children with spina bifida. J Allergy Clin Immunol 1997; 99: 600-604.
194. Porri F, Pradal M, Lemiere C, et al. Association between latex sensitization and repeated latex exposure in children. Anesthesiology 1997; 86: 599-602.
195. Tarlo SM, Sussman GL, Holness DL. Latex sensitivity in dental students and staff: a cross-sectional study. J Allergy Clin Immunol 1997; 99: 396-401.
196. Tarlo SM, Wong L, Roos J, Booth N. Occupational asthma caused by latex in a surgical glove manufacturing plant. J Allergy Clin Immunol 1990; 85: 626-631.
197. Brehler R, Theissen U, Mohr C, et al. 'Latex-fruit syndrome': frequency of cross-reacting IgE antibodies. Glove powder - a risk factor for the development of latex allergy? Allergy 1997; 52: 404-410.
198. Kelly KJ, Pearson ML, Kurup VP, et al. A cluster of anaphylactic reactions in children with spina bifida during general anesthesia: epidemiologic features, risk factors, and latex hypersensitivity. J Allergy Clin Immunol 1994; 94: 53-61.
199. Lebenbom-Mansour MH, Oesterle JR, Ownby DR, et al. The incidence of latex sensitivity in ambulatory surgical patients: a correlation of historical factors with positive serum immunoglobin E levels. Anesth Analg 1997; 85: 44-49.
200. Fuchs T, Spitzauer S, Vente C, et al. Natural latex, grass pollen, and weed pollen share IgE epitopes. J Allergy Clin Immunol 1997; 100: 356-364.
201. Veien M, Szlam F, Holden J, et al. Mechanisms of nonimmunological histamine and tryptase release from human cutaneous mast cells. Anesthesiology 2000; 92: 1074-1081.
202. Watkins J, Wild G. Improved diagnosis of anaphylactoid reactions by measurement of serum tryptase and urinary methylhistamine. Ann Fr Anesth Réanim 1993; 12: 169-172.
203. Pumphrey RS, Roberts IS. Postmortem findings after fatal anaphylactic reactions. J Clin Pathol 2000; 53: 273-276.
204. Watkins J. Immediate hypersensitivity-type reactions in anaesthesia. Allergy or otherwise, a problem or an over-statement. Theor Surg 1991; 6: 229-235.
205. Lorenz W, Neugebauer E, Uvnas B, et al. Munich consensus development conference on histamine determination. In: Uvnas B (ed.). Handbook of Experimental Pharmacology, Histamine and Histamine Antagonists, Vol. 97. Berlin, Germany: Springer, 1991: 81-92.
206. Laroche D, Dubois F, Gérard J, et al. Radioimmunoassay for plasma histamine: a study of false positive and false negative values. Br J Anaesth 1995; 74: 430-437.
207. Hansson R, Holmberg CG, Tibbling G, et al. Heparin-induced diamine oxidase increase in human blood plasma. Acta Med Scand 1966; 180: 533-536.
208. Moneret-Vautrin DA, Gueant JL, Kamel L, et al. Anaphylaxis to muscle relaxants: cross-sensitivity studied by radioimmunoassays compared to intradermal tests in 34 cases. J Allergy Clin Immunol 1988; 82: 745-752.
209. Assem ES. Anaphylactic anaesthetic reactions. The value of paper radioallergosorbent tests for IgE antibodies to muscle relaxants and thiopentone. Anaesthesia 1990; 45: 1032-1038.
210. Gueant JL, Mata E, Monin B, et al. Evaluation of a new reactive solid phase for radioimmunoassay of serum specific IgE against muscle relaxant drugs. Allergy 1991; 46: 452-458.
211. Gueant JL, Masson C, Laxenaire MC. Biological tests for diagnosing the IgE-mediate allergy to anaesthetic drugs. In: Assem K (ed.). Monographs in Allergy. Basel, Switzerland: Karger, 1992: 94-107.
212. Guilloux L, Richard-Blum S, Ville G, Motin J. Histamine release assay and radioimmunoassay for the detection of IgE antibodies against neuromuscular blocking drugs. Ann Fr Anesth Reanim 1993; 12: 182-186.
213. Fisher MM, Baldo BA. Immunoassays in the diagnosis of anaphylaxis to neuromuscular blocking drugs: the value of morphine for the detection of IgE antibodies in allergic subjects. Anaesth Intensive Care 2000; 28: 167-170.
214. Gueant JL, Mata E, Monin B. Evaluation clinique et biologique d'un test radio-immunologique de détection des IgE sériques spécifiques des curarisants. In: Galteau M, Siest G, Henny J (eds). Biologic Prospective. Paris, France: Libbey Eurotext, 1989: 737-740.
215. Guilloux L, Ricard-Blum S, Ville G, Motin J. A new radioimmunoassay using a commercially available solid support for the detection of IgE antibodies against muscle relaxants. J Allergy Clin Immunol 1992; 90: 153-159.
216. Gueant JL, Mata E, Masson C, et al. Non-specific cross-reactivity of hydrophobic serum IgE to hydrophobic drugs. Mol Immunol 1995; 32: 259-266.
217. Moneret-Vautrin DA, Finet JF, Maria Y. L'allergie au latex. Revue Française d'Allergologie 1988; 183: 235-236.
218. Assem ES, Symons IE. Anaphylaxis due to suxamethonium in a 7-year-old child: a 14-year follow-up with allergy testing. Anaesthesia 1989; 44: 121-124.
219. Moneret-Vautrin DA, Laxenaire MC. Anaphylaxis to muscle relaxants: predictive tests. Anaesthesia 1990; 45: 246-247.
220. Fisher MM, Baldo BA. Persistence of allergy to anaesthetic drugs. Anaesth Intensive Care 1992; 20: 143-146.
221. Laxenaire MC, Moneret-Vautrin DA. Le risque allergique en anesthésie-réanimation. In: Lemaire F, Desmonts JM (eds). Collection d'Anesthésiologie et de Réanimation, Vol. 17. Paris, France: Masson, 1990: 1-154.
222. Moneret-Vautrin DA, Laxenaire MC. Skin tests in diagnosis of allergy to muscle relaxants and other anaesthetic drugs. In: Assem ES (ed.). Allergic Reactions to Anaesthetics: Clinical and Basic Aspects, Vol. 30. Basel, Switzerland: Karger, 1992: 145-155.
223. Fisher MM, Bowey CJ. Intradermal compared with prick testing in the diagnosis of anaesthetic allergy. Br J Anaesth 1997; 79: 59-63.
224. Galletly DC. Comparative cutaneous histamine release by neuromuscular blocking agents. Anaesth Intensive Care 1986; 14: 365-369.
225. Levy JH, Gottge M, Szlam F, Zaffer R, McCall C. Weal and flare responses to intradermal rocuronium and cisatracurium in humans. Br J Anaesth 2000; 85: 844-849.
226. McKinnon RP, Wildsmith JA. Histaminoid reactions in anaesthesia. Br J Anaesth 1995; 74: 217-228.
227. Turjanmaa K, Palosuo T, Alenius H, et al. Latex allergy diagnosis: in vivo and in vitro standardization of a natural rubber latex extract. Allergy 1997; 52: 41-50.
228. Mata E, Gueant JL, Moneret-Vautrin DA, et al. Clinical evaluation of in vitro leukocyte histamine release in allergy to muscle relaxant drugs. Allergy 1992; 47: 471-476.
229. Sainte-Laudy J, Vallon C, Guerin JC. Analysis of membrane expression of the CD63 human basophil activation marker. Applications to allergologic diagnosis. Allerg Immunol 1994; 26: 211-214.
230. Abuaf N, Rajoely B, Ghazouani E, et al. Validation of a flow cytometric assay detecting in vitro basophil activation for the diagnosis of muscle relaxant allergy. J Allergy Clin Immunol 1999; 104: 411-418.
231. Monneret G, Benoit Y, Gutowski M, Bienvenu J. Detection of basophil activation by flow cytométrie in patients with allergy to muscle-relaxant drugs. Anesthesiology 2000; 92: 275-277.
232. Bermejo N, Guéant J, Mata E, et al. Platelet serotonin is a mediator potentially involved in anaphylactic reaction to neuromuscular blocking drugs. Br J Anaesth 1993; 70: 322-325.
233. Assem E. Release of eosinophil cationic protein (ECP) in anaphylactoid anaesthetic reactions in vivo and in vitro. Agents Actions 1994; 41: C11-C13.
234. Assem E. Leukotriene C4 release from blood cells in vitro in patients with anaphylactoid reactions to neuromuscular blockers. Agents Actions 1993; 38: C242-C244.
235. Turjanmaa K, Reunala T, Rasanen L. Comparison of diagnostic methods in latex surgical glove contact urticaria. Contact Dermatitis 1988; 19: 241-247.
236. Porri F, Pradal M, Rud C, et al. Is systematic preoperative screening for muscle relaxant and latex allergy advisable? Allergy 1995; 50: 374-377.
237. Theissen JL, Zahn P, Theissen U, Brehler R. Allergic and pseudo-allergic reactions in anesthesia. II: symptoms, diagnosis, therapy, prevention. Anasthesiol Intensivmed Notfallmed Schmerzther 1995; 30: 71-76.
238. Lieberman P. The use of antihistamines in the prevention and treatment of anaphylaxis and anaphylactoid reactions. J Allergy Clin Immunol 1990; 86: 684-686.
239. Lorenz W, Doenicke A, Schoning B, et al. H1 + H2-receptor antagonists for premedication in anaesthesia and surgery: a critical view based on randomized clinical trials with Haemaccel and various antiallergic drugs. Agents Actions 1980; 10: 114-124.
240. Hosking MP, Lennon RL, Gronert GA. Combined H1 and H2 receptor blockade attenuates the cardiovascular effects of high-dose atracurium for rapid sequence endotracheal intubation. Anesth Analg 1988; 67: 1089-1092.
241. Doenicke A, Moss J, Lorenz W, et al. Effect of oral antihistamine premedication on mivacurium-induced histamine release and side effects. Br J Anaesth 1996; 77: 421-423.
242. Moss J, Roizen MF, Nordby EJ, et al. Decreased incidence and mortality of anaphylaxis to chymopapain. Anesth Analg 1985; 64: 1197-1201.
243. Lorenz W, Duda D, Dick W, et al. Incidence and clinical importance of perioperative histamine release: randomised study of volume loading and antihistamines after induction of anaesthesia. Trial Group Mainz/Marburg. Lancet 1994; 343: 933-940.
244. Setlock MA, Cotter TP, Rosner D. Latex allergy: failure of prophylaxis to prevent severe reaction. Anesth Analg 1993; 76: 650-652.
245. Kwittken PL, Sweinberg SK, Campbell DE, Pawlowski NA. Latex hypersensitivity in children: clinical presentation and detection of latex-specific immunoglobulin E. Pediatrics 1995; 95: 693-699.
246. Powell JA, Maycock EJ. Anaphylactoid reaction to ranitidine in an obstetric patient. Anaesth Intensive Care 1993; 21: 702-703.
247. Patterson LJ, Milne B. Latex anaphylaxis causing heart block: role of ranitidine. Can J Anaesth 1999; 46: 776-778.
248. McKinnon RP. Allergic reactions during anaesthesia. Curr Opinion Anaesth 1996; 9: 267-270.
249. Birnbaum J, Porri F, Pradal M, Charpin D, Vervloet D. Allergy during anaesthesia. Clin Exp Allergy 1994; 24: 915-921.
250. Ljungstrom KG, Renck H, Hedin H, Richter W, Wiholm BE. Hapten inhibition and dextran anaphylaxis. Anaesthesia 1988; 43: 729-732.
251. Berg EM, Fasting S, Sellevold OF. Serious complications with dextran-70 despite hapten prophylaxis. Is it best avoided prior to delivery? Anaesthesia 1991; 46: 1033-1035.
252. Ljungstrom KG, Willman B, Hedin H. Hapten inhibition of dextran anaphylaxis. Nine years of post-marketing surveillance of dextran 1. Ann Fr Anesth Reanim 1993; 12: 219-222.
253. Hedin H, Ljungstrom KG. prevention of dextran anaphylaxis. Ten years experience with hapten dextran. Int Arch Allergy Immunol 1997; 113: 358-359.
254. Vervloet D, Arnaud A, Senft M, et al. Anaphylactic reactions to suxamethonium: prevention of mediator release by choline. J Allergy Clin Immunol 1985; 76: 222-225.
255. Thomas H, Eledjam JJ, Macheboeuf M, et al. Rapid preoperative immunotherapy in a patient allergic to muscle relaxants. Eur J Anaesthesiol 1988; 5: 385-389.
256. Moneret-Vautrin DA, Kanny G, Gueant JL, Widmer S, Laxenaire MC. Prevention by monovalent haptens of IgE-dependent leucocyte histamine release to muscle relaxants. Int Arch Allergy Immunol 1995; 107: 172-175.
257. Laxenaire MC. Choc anaphylactique peranesthésique: conduite à tenir. Ann Fr Anesth Reanim 1997; 16: 102-104.
258. Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Anaphylaxis. Circulation 2000; 102: I-241-I-243.
259. American Academy of Allergy and Immunology Board of Directors. The use of epinephrine in the treatment of anaphylaxis. J Allergy Clin Immunol 1994; 94: 666-668.
260. Ewan PW. Anaphylaxis. BMJ 1998; 316: 1442-1445.
261. Powers RD, Donowitz LG. Endotracheal administration of emergency medications. South Med J 1984; 77: 340-341, 346.
262. Heilborn H, Hjemdahl P, Daleskog M, Adamsson U. Comparison of subcutaneous injection and high-dose inhalation of epinephrine - implications for self-treatment to prevent anaphylaxis. J Allergy Clin Immunol 1986; 78: 1174-1179.
263. Plomley RF, Czarny D. Inhaled adrenaline in the treatment of anaphylaxis. Med J Aust 1988; 149: 564.
264. Simons FE, Roberts JR, Gu X, Simons KJ. Epinephrine absorption in children with a history of anaphylaxis. J Allergy Clin Immunol 1998; 101: 33-37.
265. Alexander R, Pappachan R, Smith GB, Taylor BL. Treatment of acute anaphylaxis. Avoid subcutaneous or intramuscular adrenaline. Br Med J 1995; 311: 1434-1435.
266. Campbell S. Treatment of acute anaphylaxis. Expressing the dose of adrenaline in milligrams is easier. BMJ 1995; 311: 1435.
267. Raper RF, Fisher MM. Profound reversible myocardial depression after anaphylaxis. Lancet 1988; 1: 386-388.
268. Levy JH. New concepts in the treatment of anaphylactoid reactions in anesthesia. Ann Fr Anesth Reanim 1993; 12: 223-227.
269. Lee ML. Glucagon in anaphylaxis. J Allergy Clin Immunol 1982; 69: 331-332.
270. Zaloga GP, DeLacey W, Holmboe E, Chernow B. Glucagon reversal of hypotension in a case of anaphylactoid shock. Ann Intern Med 1986; 105: 65-66.
271. Compton J. Use of glucagon in intractable allergic reactions and as an alternative to epinephrine: an interesting case review. J Emerg Nurs 1997; 23: 45-47.
272. Schleimer RP. The mechanisms of antiinflammatory steroid action in allergic diseases. Annu Rev Pharmacol Toxicol 1985; 25: 381-412.
Keywords:

DIAGNOSIS, LABORATORY TECHNIQUES AND PROCEDURES, immunological tests, serological tests, skin tests; EPIDEMIOLOGY; HYPERSENSITIVITY, latex allergy; HYPERSENSITIVITY, DELAYED; HYPERSENSITIVITY, IMMEDIATE, anaphylaxis; THERAPEUTICS, drug therapy

© 2002 European Academy of Anaesthesiology