These parameters were developed by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma and Immunology; the American College of Allergy, Asthma and Immunology; and the Joint Council of Allergy, Asthma and Immunology. The American Academy of Allergy, Asthma and Immunology (AAAAI) and the American College of Allergy, Asthma and Immunology (ACAAI) have jointly accepted responsibility for establishing "The diagnosis and management of anaphylaxis: an updated practice parameter." This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individual, including those who served on the Joint Task force, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma and Immunology. These parameters are not designed for use by pharmaceutical companies in drug promotion. This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients.

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The diagnosis and management of anaphylaxis: an updated practice parameter.

Background Anaphylactic and anaphylactoid reactions occurring during anesthesia remain a major cause of concern for anesthesiologists. The authors report the results of a 2-yr survey of such reactions observed during anesthesia in France. Methods Between January 1, 1999, and December 31, 2000, 789 patients who experienced immune-mediated (anaphylaxis) or nonimmune-mediated (anaphylactoid) reactions were referred to one of the 40 participating centers. Anaphylaxis was diagnosed on the basis of clinical history, skin tests, and/or specific immunoglobulin E assay. Results Anaphylactic and anaphylactoid reactions were diagnosed in 518 cases (66%) and 271 cases (34%), respectively. The most common causes of anaphylaxis were neuromuscular blocking agents (NMBAs) (n = 306, 58.2%), latex (n = 88, 16.7%), and antibiotics (n = 79, 15.1%). Rocuronium (n = 132, 43.1%) and succinylcholine (n = 69, 22.6%) were the most frequently incriminated NMBAs. Cross-reactivity between NMBAs was observed in 75.1% of cases of anaphylaxis to an NMBA. No difference was observed between anaphylactoid and anaphylactic reactions when the incidences of atopy, asthma, or drug intolerance were compared. However, atopy, asthma, and food allergy were significantly more frequent in the case of latex allergy when compared with NMBA allergy. Clinical manifestations were more severe in anaphylaxis. The positive predictive value of tryptase for the diagnosis of anaphylaxis was 92.6%; the negative predictive value was 54.3%. The diagnostic value of specific NMBA immunoglobulin E assays was confirmed. Conclusions These results further corroborate the need for systematic screening in the case of anaphylactoid reaction during anesthesia and for the constitution of allergoanesthesia centers to provide expert advice to anesthesiologists and allergists.

Anaphylactic and Anaphylactoid Reactions Occurring during Anesthesia in France in 1999–2000

Hydroxyethyl starch (HES) is one of the most frequently used plasma substitutes. A variety of different HES solutions exist worldwide, which differ greatly in their pharmacological properties. HES is classified according to its manufactured or in vitro molecular weight (MW) into high MW (450–480 kDa), medium MW (200 kDa), and low MW (70 kDa) starch preparations. However, this is not sufficient, because as HES is metabolized in vivo, its MW changes, and it is the in vivo MW which is responsible for the therapeutic and adverse effects of each HES. The rate of metabolization depends mainly on the degree of hydroxyethyl substitution (ranging from 0.4 to 0.7), and the C2/C6 ratio of hydroxyethylation. A high degree of substitution and a high C2/C6 ratio lead to a slow metabolization of HES, resulting in a large in vivo MW. Slowly degradable high MW HES 450/0.7 and medium MW HES 200/0.62 have a high in vivo MW and are eliminated slowly via the kidneys. As a result, these starches have a relatively long-lasting volume effect. When infusing higher volumes ( > 1500 ml) are infused, large molecules accumulate in the plasma. This can result in bleeding complications due to decreased factor VIII/von Willebrand factor, platelet function defects, incorporation into fibrin clots, and an unfavorable effect on rheological parameters. Rapidly degradable medium MW HES 200/0.5 or low MW HES 70/0.5 are quickly split in vivo into smaller, more favorable molecule sizes, resulting in faster renal elimination, shorter volume effect, and fewer adverse effects on coagulation and rheological parameters. For historical and marketing reasons, only slowly degradable, high MW HES (480/0.7) is available in the United States. In Europe, a large variety of HES solutions are available, dominated by medium MW, easily degradable HES (200/0.5). Because of increasing international competition and the availability of newly developed starches, it is important to be aware of the pharmacological properties of HES and the advantages and disadvantages of the individual preparations.

An international view of hydroxyethyl starches

Severe anaphylaxis is a systemic reaction affecting two or more organs or systems and is due to the release of active mediators from mast cells and basophils. A four-grade classification routinely places severe anaphylaxis in grades 3 and 4 (death could be graded as grade 5). Studies are underway to determine the prevalence of severe and lethal anaphylaxis in different populations and the relative frequencies of food, drug, latex and Hymenoptera anaphylaxis. These studies will also analyse the risk arising from the lack of preventive measures applied in schools (personalized management protocols) and from the insufficient use of self-injected adrenalin.Allergy-related conditions may account for 0.2–1% of emergency consultations. Severe anaphylaxis affects 1–3 per 10 000 people, but for the United States and Australia figures are even higher. It is estimated to cause death in 0.65–2% of patients, i.e. 1–3 per million people. An increased prevalence has been revealed by monitoring hospitalized populations by reference to the international classification of disease (ICD) codes. The relative frequency of aetiological factors of allergy (food, drugs, insects and latex) varies in different studies. Food, drug and Hymenoptera allergies are potentially lethal. The risk of food-mediated anaphylaxis can be assessed from the number of personalized management protocols in French schools: 0.065%. Another means of assessment may be the rate of adrenalin prescriptions. However, an overestimation of the anaphylaxis risk may result from this method (0.95% of Canadian children). Data from the literature leads to several possibilities. First, a definition of severe anaphylaxis should be agreed. Secondly, prospective, multicentre enquiries, using ICD codes, should be implemented. Moreover, the high number of anaphylaxis cases for which the aetiology is not identified, and the variation in aetiology in the published series, indicate that a closer cooperation between emergency specialists and allergists is essential.

Epidemiology of life-threatening and lethal anaphylaxis: a review

With the development of a new generation of hydroxyethyl starches (HES), there has been renewed interest in their clinical potential. High doses of first- and second-generation HES were associated with adverse effects on renal function, coagulation, and tissue storage, thereby limiting their clinical applicability. Newer HES products have lower molar substitution and in vivo molecular weight, resulting in more rapid metabolism and clearance. In this review article, the differences between HES generations are highlighted, with particular emphasis on the improved safety profile of the third generation products. These improvements have been achieved with no loss of efficacy, and they contradict the assumption that efficacy of HES solutions is directly linked to plasma concentration. The impact of source material on structure and pharmacokinetics is highlighted, and the role of the carrier solution is critically assessed.

Hydroxyethyl starches: different products--different effects.

Resume L'evolution dans les pratiques transfusionnelles conduit a utiliser abondamment les substitus colloidaux du plasma dont la gamme s'est recemment enrichie par la commercialisation des amidons. Le choix des substituts repose en partie sur la connaissance de leurs effets secondaires, dont les reactions anaphylactoides. Le but de ce travail a ete d'apprecier l'incidence et la gravite des reactions en fonction des types de substituts disponibles en France, de rechercher d'eventuels facteurs de risque et de determiner le mecanisme des reactions. L'enquete a ete prospective, realisee dans 49 etablissements hospitaliers publics et prives dissemines sur tout le territoire francais, et a dure 15 mois (juin 1991 a octobre 1992). Une feuille de recueil des donnees etait remplie pour tout patient a qui un substitut etait administre, qu'il y ait ou non incident. En cas d'accident, un bilan immunoallergologique etait realise en 2 temps : immediat pour permettre le dosage de tryptase serique, anticorps antigelatines, methylhistamine urinaire, et 4 a 6 semaines apres pour realiser les tests allergologiques cutanes. Le collectif etudie a ete de 19 593 patients qui ont recu des gelatines (48,1 %), des amidons (26,7 %), des albumines (15,7 %) et des dextrans (9,5 %). Il y a eu 43 reactions anaphylactoides representant une incidence globale de reactions de 0,219 % soit 1 reaction pour 456 patients traites. L'incidence a ete differente suivant les substituts : gelatines : 0,345 %, dextrans : 0,273 %, albumines : 0,099 %, amidons : 0,058 %. Dans 20 % des cas, ces reactions ont ete severes, de grade III ou IV. Par une analyse multivariee, 4 facteurs de risque ont ete isoles, independants l'un de l'autre : il s'agit de l'administration de gelatines (Odds Ratio = OR : 4,81), de dextrans (OR = 3,83) ; les antecedents d'allergie medicamenteuse (OR = 3,16), le sexe masculin (OR = 1,98). L'estimation du risque relatif de reaction anaphylactoide d'un substitut par rapport a l'autre a montre qu'avec les amidons le risque etait 6 fois moindre qu'avec les gelatines, 4,7 fois moindre qu'avec les dextrans. Le risque represente par les albumines etait 3,4 fois moindre qu'avec les gelatines et pratiquement identique a celui des amidons. Le bilan immunoallergologique n'a pu etre realise que chez 15 patients ayant recu des gelatines (Plasmion®). La preuve d'une anaphylaxie IgE-dependante a pu etre apportee chez 7 d'entre eux. En conclusion, il est apparu que, pour reduire au maximum le risque de reaction anaphylactoide, on devrait eviter d'utiliser les gelatines et les dextrans en cas d'allergie medicamenteuse anterieure. Il est necessaire de pratiquer un bilan allergologique en cas d'accident car celui-ci peut etre lie a la presence d'anticorps, cc qui contre-indiquerait l'administration ulterieure du substitut incrimine.

Réactions anaphylactoïdes aux substituts colloïdaux du plasma : incidence, facteurs de risque, mécanismes. Enquête prospective multicentrique française

Changes in transfusion behaviour induce a widespread use of colloid plasma substitutes, the range of which has recently been enlarged by the marketing of starch derivatives The product chosen depends, at least in part, on its adverse effects, anaphylactoid reactions being a part of these This study aimed to discover the frequency and severity of these reactions according to the type of substitute available in France, to look for possible risk factors, and determine the mechanisms involved A prospective inquiry was carried out in 49 public and private hospitals spread throughout France It lasted for 15 months, between June 1991 and October 1992 A data sheet was filled in for each patient who was given a plasma substitute, whether or not there was an incident When a reaction did occur, an assessment was carried out in two stages: straightaway, with the measurement of the concentrations of serum tryptase, antigelatin antibodies, urinary methylhistamine; and four to six weeks later, with skin tests A series of 19593 patients was thus collected: 481% were given gelatins, 267% starches, 157% albumin, and 95% dextrans 43 anaphylactoid reactions were recorded, giving an overall frequency of 0219%, or 1 reaction for 456 patients The frequency differed according to the substitute considered: 0345% for gelatins, 0273% for dextrans, 0099% for albumin, and 0058% for starches These reactions (grades III and IV) were serious in 20% of cases Multivariate analysis revealed four independent risk factors: giving gelatins (odds ratio: 481), giving dextrans (odds ratio: 383), a history of drug allergy (odds ratio: 316), and being male (odds ratio: 198) The relative risks of anaphylactoid reactions due to one type of substitute with respect to another were estimated to be 6 times less for starches with respect to gelatins, and 47 times less than with dextrans The relative risk of albumin is 34 times less than that of gelatins, and almost identical to that of the starches An immuno-allergological assessment was only carried out in 15 patients who had been given a gelatin (Plasmion) IgE-dependent anaphylaxis was proven in 7 of these To conclude, it was shown that gelatins and dextrans should be avoided in patients with a known history of drug allergy When a reaction does occur, an allergological assessment must be carried out, as this may be due to specific antibodies Should this prove to be the case, that particular substitute would be contraindicated for the rest of the patient's life

C. Charpentier

Papers

Réactions anaphylactoïdes aux substituts colloïdaux du plasma : incidence, facteurs de risque, mécanismes. Enquête prospective multicentrique française

[Anaphylactoid reactions to colloid plasma substitutes: incidence, risk factors, mechanisms. A French multicenter prospective study].

Réactions anaphylactoïdes aux substituts colloïdaux du plasma : incidence, facteurs de risque, mécanismes