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      Sugammadex and rocuronium-induced anaphylaxis

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          Abstract

          Perioperative anaphylaxis is a life-threatening clinical condition that is typically the result of drugs or substances used for anesthesia or surgery. The most common cause of anaphylaxis during anesthesia is reportedly neuromuscular blocking agents. Of the many muscle relaxants that are clinically available, rocuronium is becoming popular in many countries. Recent studies have demonstrated that succinylcholine (but also rocuronium use) is associated with a relatively high rate of IgE-mediated anaphylaxis compared with other muscle relaxant agents. Sugammadex is widely used for reversal of the effects of steroidal neuromuscular blocking agents, such as rocuronium and vecuronium. Confirmed cases of allergic reactions to clinical doses of sugammadex have also been recently reported. Given these circumstances, the number of cases of hypersensitivity to either sugammadex or rocuronium is likely to increase. Thus, anesthesiologists should be familiar with the epidemiology, mechanisms, and clinical presentations of anaphylaxis induced by these drugs. In this review, we focus on the diagnosis and treatment of anaphylaxis to sugammadex and neuromuscular blocking agents. Moreover, we discuss recent studies in this field, including the diagnostic utility of flow cytometry and improvement of rocuronium-induced anaphylaxis with the use of sugammadex.

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          Most cited references54

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          Identification of a mast cell specific receptor crucial for pseudo-allergic drug reactions

          Mast cells are primary effectors in allergic reactions, and may have significant roles in diseases by secreting histamine and various inflammatory and immunomodulatory substances 1,2 . While classically they are activated by IgE antibodies, a unique property of mast cells is their antibody-independent responsiveness to a range of cationic substances, collectively called basic secretagogues, including inflammatory peptides and drugs associated with allergic-type reactions 1,3 . Roles for these substances in pathology have prompted a decades-long search for their receptor(s). Here we report that basic secretagogues activate mouse mast cells in vitro and in vivo through a single receptor, MrgprB2, the orthologue of the human G-protein coupled receptor (GPCR) MrgprX2. Secretagogue-induced histamine release, inflammation, and airway contraction are abolished in MrgprB2 null mutant mice. Further, we show that most classes of FDA-approved peptidergic drugs associated with allergic-type injection-site reactions also activate MrgprB2 and MrgprX2, and that injection-site inflammation is absent in mutant mice. Finally, we determine that MrgprB2 and MrgprX2 are targets of many small molecule drugs associated with systemic pseudo-allergic, or anaphylactoid, reactions; we show that drug-induced symptoms of anaphylactoid responses are significantly reduced in knockout mice, and we identify a common chemical motif in several of these molecules that may help predict side effects of other compounds. These discoveries introduce a mouse model to study mast cell activation by basic secretagogues and identify MrgprX2 as a potential therapeutic target to reduce a subset of drug-induced adverse effects.
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            Anaphylaxis fatalities and admissions in Australia.

            Detailed data on fatal anaphylaxis are limited, with national anaphylaxis fatality data for the United Kingdom and food-induced anaphylaxis fatality data for the United States. Time trends for anaphylaxis fatalities are not available. We examined causes, demographics, and time trends for anaphylaxis fatalities in Australia between January 1997 and December 2005 and compared these with findings for anaphylaxis admissions. Data on anaphylaxis deaths and hospital admissions were extracted from a national database. Death certificate codes were analyzed to determine the likely cause and associated comorbidities. There were 112 anaphylaxis fatalities in Australia over 9 years. Causes were as follows: food, 7 (6%); drugs, 22 (20%); probable drugs, 42 (38%); insect stings, 20 (18%); undetermined, 15 (13%); and other, 6 (5%). All food-induced anaphylaxis fatalities occurred between 8 and 35 years of age with female preponderance, despite the majority of food-induced anaphylaxis admissions occurring in children less than 5 years of age. Most insect sting-induced anaphylaxis deaths occurred between 35 and 84 years almost exclusively in male subjects, although bee sting-induced admissions peak between 5 and 9 years of age with a male/female ratio of 2.7. However, most drug-induced anaphylaxis deaths occurred between 55 and 85 years with equal sex distribution similar to drug-induced anaphylaxis admissions. There was no evidence of an increase in death rates for food-induced anaphylaxis, despite food-induced anaphylaxis admissions increasing approximately 350%. In contrast, drug-induced anaphylaxis deaths increased approximately 300% compared with an approximately 150% increase in drug-induced anaphylaxis admissions. The demographics for anaphylaxis deaths are different to those for anaphylaxis presentations. Anaphylaxis mortality rates remain low and stable, despite increasing anaphylaxis prevalence, with the exception of drug-induced anaphylaxis deaths, which have increased.
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              Anaphylactic and anaphylactoid reactions occurring during anesthesia in France in 1999-2000.

              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. 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. 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. 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.
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                Author and article information

                Contributors
                +81-027-220-8454 , takazawt@gunma-u.ac.jp
                Journal
                J Anesth
                J Anesth
                Journal of Anesthesia
                Springer Japan (Tokyo )
                0913-8668
                1438-8359
                8 December 2015
                8 December 2015
                2016
                : 30
                : 290-297
                Affiliations
                [ ]Department of Anesthesiology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, 371-8511 Japan
                [ ]Department of Anesthesiology, Juntendo Tokyo Koto Geriatric Medical Center, 3-3-20 Shinsuna, Koto-Ku, Tokyo, 136-0075 Japan
                [ ]Service d’anesthésie-réanimation chirurgicale, Nouvel hôpital civil, hôpitaux universitaires de Strasbourg, 1, place de l’Hôpital, BP 426, 67091 Strasbourg Cedex, France
                Article
                2105
                10.1007/s00540-015-2105-x
                4819478
                26646837
                d94fed50-0ea8-4b10-bf2f-585ec1ad0dab
                © The Author(s) 2015

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 1 November 2015
                : 11 November 2015
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001691, Japan Society for the Promotion of Science;
                Award ID: 15K10533
                Award Recipient :
                Categories
                Invited Review Article
                Custom metadata
                © Japanese Society of Anesthesiologists 2016

                Anesthesiology & Pain management
                sugammadex,rocuronium,anaphylaxis,neuromuscular blocking agent,flow cytometry

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