Hugh A. Sampson, MD, Anne Munoz-Furlong, BA, S. Allan Bock, MD, Cara Schmitt, MS, Robert Bass, MD, Badrul A. Chowdhury, MD, Wyatt W. Decker, MD, Terence J. Furlong, MS, Stephen J. Galli, MD, David B. Golden, MD, Rebecca S. Gruchalla, MD, Allen D. Harlor, Jr, MD, David L. Hepner, MD, Marilyn Howarth, MD, Allen P. Kaplan, MD, Jerrold H. Levy, MD, Lawrence M. Lewis, MD, Phillip L. Lieberman, MD, Dean D. Metcalfe, MD, Ramon Murphy, MD, Susan M. Pollart, MD, Richard S. Pumphrey, MD, Lanny J. Rosenwasser, MD, F. Estelle Simons, MD, Joseph P. Wood, MD, and Carlos A. Camargo, Jr, MD New York, NY, Fairfax and Charlottesville, Va, Boulder and Denver, Colo, Baltimore, Rockville, and Bethesda, Md, Rochester, Minn, Stanford, Calif, Dallas, Tex, Eugene, Ore, Boston, Mass, Philadelphia, Pa, Charleston, SC, Atlanta, Ga, St Louis, Mo, Cordova, Tenn, Scottsdale, Ariz, Manchester, United Kingdom, and Winnipeg, Manitoba, Canada

https://www.jacionline.org/article/S0091-6749(05)00088-6/pdf

Symposium on the Definition and Management of Anaphylaxis: Summary report

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

Anesthesiologists use a myriad of drugs during the provision of an anesthetic. Many of these drugs have side effects that are dose related, and some lead to severe immune-mediated adverse reactions. Anaphylaxis is the most severe immune-mediated reaction; it generally occurs on reexposure to a specific antigen and requires the release of proinflammatory mediators. Anaphylactoid reactions occur through a direct non-immunoglobulin E-mediated release of mediators from mast cells or from complement activation. Muscle relaxants and latex account for most cases of anaphylaxis during the perioperative period. Symptoms may include all organ systems and present with bronchospasm and cardiovascular collapse in the most severe cases. Management of anaphylaxis includes discontinuation of the presumptive drug (or latex) and anesthetic, aggressive pulmonary and cardiovascular support, and epinephrine. Although a serum tryptase confirms the diagnosis of an anaphylactic reaction, the offending drug can be identified by skin-prick, intradermal testing, or serologic testing. Prevention of recurrences is critical to avoid mortality and morbidity.

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Anaphylaxis during the perioperative period.

Mast cells, which are granulocytes found in peripheral tissue, play a central role in inflammatory and immediate allergic reactions. beta-Tryptase is a neutral serine protease and is the most abundant mediator stored in mast cell granules. The release of beta-tryptase from the secretory granules is a characteristic feature of mast cell degranulation. While its biological function has not been fully clarified, mast cell beta-tryptase has an important role in inflammation and serves as a marker of mast cell activation. beta-Tryptase activates the protease activated receptor type 2. It is involved in airway homeostasis, vascular relaxation and contraction, gastrointestinal smooth muscle activity and intestinal transport, and coagulation. Serum mast cell beta-tryptase concentration is increased in anaphylaxis and in other allergic conditions. It is increased in systemic mastocytosis and other haematological conditions. Serum beta-tryptase measurements can be used to distinguish mast cell-dependent reactions from other systemic disturbances such as cardiogenic shock, which can present with similar clinical manifestations. Increased beta-tryptase levels are highly suggestive of an immunologically mediated reaction but may also occur following direct mast cell activation. Patients with increased mast cell beta-tryptase levels must be investigated for an allergic cause. However, patients without increased mast cell tryptase levels should be investigated if the clinical picture suggests severe anaphylaxis.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2044.2004.03757.x

Mast cell tryptase: a review of its physiology and clinical significance.

The present approach to the diagnosis, management and follow-up of anaphylaxis during anaesthesia varies in the Scandinavian countries. The main purpose of these Scandinavian Clinical Practice Guidelines is to increase the awareness about anaphylaxis during anaesthesia amongst anaesthesiologists. It is hoped that increased focus on the subject will lead to prompt diagnosis, rapid and correct treatment, and standardised management of patients with anaphylactic reactions during anaesthesia across Scandinavia. The recommendations are based on the best available evidence in the literature, which, owing to the rare and unforeseeable nature of anaphylaxis, mainly includes case series and expert opinion (grade of evidence IV and V). These guidelines include an overview of the epidemiology of anaphylactic reactions during anaesthesia. A treatment algorithm is suggested, with emphasis on the incremental titration of adrenaline (epinephrine) and fluid therapy as first-line treatment. Recommendations for primary and secondary follow-up are given, bearing in mind that there are variations in geography and resources in the different countries. A list of National Centres from which anaesthesiologists can seek advice concerning follow-up procedures is provided. In addition, an algorithm is included with advice on how to manage patients with previous suspected anaphylaxis during anaesthesia. Lastly, Appendix 2 provides an overview of the incidence, mechanisms and possibilities for follow-up for some common drug groups.

/pdf/scandinavian-clinical-practice-guidelines-on-the-diagnosis-4idmi9fhpm.pdf

Scandinavian Clinical Practice Guidelines on the diagnosis, management and follow-up of anaphylaxis during anaesthesia

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.

M.-C. Laxenaire

Papers

Allergic reactions occurring during anaesthesia