Neuromuscular blocking agents induced anaphylaxis: Results and trends of a French pharmacovigilance survey from 2000 to 2012.

BACKGROUND: Perioperative anaphylaxis mainly involves neuromuscular blocking agents (NMBAs) with an IgE-mediated mechanism. In France, this life-threatening condition is reported by anesthetists and allergologists, and two safety alerts concerning suxamethonium were raised in 2011 and 2012. This led to start a national survey over the 2000-2012 period which objectives were to provide a descriptive analysis, to estimate incidence rates, and to analyze the trends over this period. METHODS: The French pharmacovigilance database was retrospectively queried for all the available NMBAs. Anaphylaxis cases with elevated tryptase and positive skin tests were qualified as "confirmed cases." Subgroup analysis compared atracurium and cisatracurium vs suxamethonium and rocuronium. RESULTS: A total of 680 confirmed cases and 944 nonconfirmed cases were identified. Suxamethonium was the most implied NMBA (64%). Incidence rates (according to sales data) of suxamethonium and rocuronium were, respectively, 10- and 13-folds higher than those of the others NMBAs, regardless the confirmed/nonconfirmed status. Cisatracurium incidence rates remained stable over the period, while suxamethonium and atracurium increased and rocuronium first decreased but re-increased after 2006. Male patients were more frequent in the subgroup "atracurium-cisatracurium" (P = .019), whereas obesity and emergency setting were more frequent in the subgroup "rocuronium-suxamethonium." Shared characteristics were the poorly documented previous exposure to NMBA(s) and an insufficient adherence of patients to perform skin tests, showing the need to improve this procedure. CONCLUSION: Suxamethonium and rocuronium are markedly more involved in perioperative anaphylaxis than the other available NMBAs. Patients should be more informed about their perioperative anaphylaxis and its consequences.

Drug hypersensitivity.

Before the arrival of modern pharmacotherapy, drug hypersensitivity reactions were virtually unknown. Toxicity from the many plant-, animal- and inorganic material-derived remedies must have been much more common. One famous example is the intoxications from mercury, which has been used in many ailments, but particularly for the treatment of syphilis. It was only in the 19th century when more and more active principles from e.g. plants were identified, and when the observations of skin reactions became more prevalent. In 1877, Heinrich Köbner used for the first time the term 'drug exanthema' (Arznei-Exanthem). Since then, many different types of exanthemas from the mild macular-papular forms to the severe life-threatening bullous exanthemas such as toxic epidermal necrolysis have been observed from numerous drugs. The systematic investigation of severe drug reactions has only started in the second half of the 20th century, parallel to the increasing knowledge in immunology. Drug hypersensitivity reactions still remain one of the most challenging problems in allergology due to their manifold clinical manifestations and their very diverse pathophysiology. The introduction of new drugs and in turn the emergence of new hypersensitivity reactions will remain a challenge in the future.

Introduction: Szczeklik's contributions to our understanding of aspirin, NSAIDs, asthma, and allergy.

Andrew Szczeklik was born in 1938 and died on Feb 3rd, 2012. He was the most influential expert in the field of aspirin and NSAID sensitivity reactions and associated diseases in the world. This edition of NACAI is dedicated to Andrew. In the introductory chapter, we elected to highlight his accomplishments as reflected in his publications. Andrew published at least 503 articles including many invited review articles. We present 20 of his most important publications all of which contributed significantly to our understanding of these diseases.

Penicillin skin testing: potential implications for antimicrobial stewardship.

As the progression of multidrug-resistant organisms and lack of novel antibiotics move us closer toward a potential postantibiotic era, it is paramount to preserve the longevity of current therapeutic agents. Moreover, novel interventions for antimicrobial stewardship programs are integral to combating antimicrobial resistance worldwide. One unique method that may decrease the use of second-line antibiotics (e.g., fluoroquinolones, vancomycin) while facilitating access to a preferred ß-lactam regimen in numerous health care settings is a penicillin skin test. Provided that up to 10% of patients have a reported penicillin allergy, of whom ~10% have true IgE-mediated hypersensitivity, significant potential exists to utilize a penicillin skin test to safely identify those who may receive penicillin or a ß-lactam antibiotic. In this article, we provide information on the background, associated costs, currently available literature, pharmacists' role, antimicrobial stewardship implications, potential barriers, and misconceptions, as well as future directions associated with the penicillin skin test.

History and classification of anaphylaxis.

Anaphylaxis as the maximal variant of an acute systemic hypersensitivity reaction can involve several organ systems, particularly the skin, respiratory tract, gastrointestinal tract and the cardiovascular system. The severity of anaphylactic reaction is variable and can be classified into severity grades I-IV. Some reactions are fatal. Most frequent elicitors of anaphylaxis are foods in childhood, later insect stings and drugs. The phenomenon itself has been described in ancient medical literature, but was actually recognized and named at the beginning of the 20th century by Charles Richet and Paul Portier. In the course of experiments starting on the yacht of the Prince of Monaco and continued in the laboratory in Paris, they tried to immunize dogs with extracts of Physalia species in an attempt to develop an antitoxin to the venom of the Portuguese man-of-war. While Charles Richet believed that anaphylaxis was a 'lack of protection', it has become clear that an exaggerated immune reaction, especially involving immunoglobulin E antibodies, is the underlying pathomechanism in allergic anaphylaxis besides immune complex reactions. Non-immunologically mediated reactions leading to similar clinical symptomatology have been called 'anaphylactoid' or 'pseudo-allergic'--especially by Paul Kallos--and are now called 'non-immune anaphylaxis' according to a consensus of the World Allergy Organization (WAO). The distinction of different pathophysiological processes is important since non-immune anaphylaxis cannot be detected by skin test or in vitro allergy diagnostic procedures. History and provocation tests are crucial. The intensity of the reaction is not only influenced by the degree of sensitization but also by concomitant other factors as age, simultaneous exposure to other allergens, underlying infection, physical exercise or psychological stress or concomitant medication (e.g. beta-blockers, NSAIDs); this phenomenon has been called augmentation or summation anaphylaxis.

[AIDS through blood contamination (early 1980s) and urethane shock (1975)].

1) AIDS contracted through contaminated blood was first discovered in the early 1980s, and related law suits are now underway. The contamination of the blood is considered to ba a shared responsibility of the "government," "medical establishments" and "industry." The revision of the Pharmaceutical Affairs Law in 1979 gave the authority for commanding the recall of products to the Health and Welfare Ministry. This was a lesson learned from past cases of drug-induced suffering. However, the ministry did nothing regarding the blood contaminated with the AIDS virus. 2) "Urethane shock (drug-induced suffering)" occurred in 1975. Although it occurred before the revision of the Pharmaceutical Affairs Law, the Health and Welfare Ministry took the administrative measure of "an immediate recall," because the antipyretic analgesic injections used all over the country at that time contained 0.15 to 0.3g of urethane which is a carcinogenic substance, per ampoule. 3) Even the revision of the Pharmaceutical Affairs Law could not prevent cases of drug-induced suffering. I think that all concerned should have a full understanding, receive fair judgement and be encouraged to prevent such mistakes in the future.

[Latex allergy. Risk factors in anesthesiology]. / Allergie au latex. Facteurs de risques en anesthésiologie.

Epidemiological studies show an increasing frequency of the responsibility of latex in allergy accidents during operations (1). The frequency of the responsibility of latex in the anaesthetic medium develops moreover in parallel with the frequency of latex allergy generally (in the professional and non-professional fields).

The development of cholecystography: the first fifty years.

Visualization of the gallbladder by x-ray was first achieved in 1923 by the intravenous introduction into the body of a halogenated compound which was excreted by the liver into the bile ducts and gallbladder [1--4]. This was the first time that visualization of an organ had been accomplished by introducing a substance into the body and obtaining a roentgenogram after the substance had been metabolized and localized primarily in one organ. Previously, visualization of an organ had been achieved only by introducing a substance opaque to the x-ray directly into the lumen and obtaining a roentgenogram to outline its inner wall. By 1925 visualization of the gallbladder had also been accomplished by the oral administration of halogenated compounds [5,6]. The drugs employed for intravenous and oral cholecystography had been synthesized specifically for that purpose based on earlier experimental work of other investigators. The following account describes in detail the experimental background of cholecystography, its origin, and its development and use during the ensuing fifty years.