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There is a paucity of data supporting existing management guidelines. Therapeutic recommendations include the need for the timely administration of appropriate doses of aggressive fluid resuscitation and intravenous (IV) adrenaline in RA. The preferred second\u2010line vasopressor (noradrenaline, vasopressin, metaraminol and dopamine) is unknown. Most guidelines recommend IV glucagon for patients on beta\u2010blockers, despite a lack of evidence. The use of methylene blue or extracorporeal life support (ECLS) is also suggested as rescue therapy. Despite recent advances in understanding the pathogenesis of anaphylaxis, the factors that lead to a lack of response to the initial adrenaline and thus RA are unclear. Genetic factors, such as deficiency in platelet activating factor\u2010acetyl hydrolase or hereditary alpha\u2010tryptasaemia, mastocytosis may modulate reaction severity or response to treatment. Further research into the underlying pathophysiology of RA may help define potential new therapeutic approaches and reduce the morbidity and mortality of anaphylaxis.<\/jats:p>","DOI":"10.1111\/cea.14514","type":"journal-article","created":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T21:28:58Z","timestamp":1718227738000},"page":"470-488","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Management of Refractory Anaphylaxis: An Overview of Current Guidelines"],"prefix":"10.1111","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4118-6385","authenticated-orcid":false,"given":"Guillaume","family":"Pouessel","sequence":"first","affiliation":[{"name":"Department of Paediatrics Children's Hospital  Roubaix France"},{"name":"Paediatric Pulmonology and Allergy Department Jeanne de Flandre Hospital, CHU Lille  Lille France"},{"name":"Univ Lille, ULR 2694: METRICS  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy\u00a0E.","family":"Dribin","sequence":"additional","affiliation":[{"name":"Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Division of Emergency Medicine Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"},{"name":"Department of Pediatrics University of Cincinnati College of Medicine  Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Tacquard","sequence":"additional","affiliation":[{"name":"Department of Anaesthesia and Intensive Care Strasbourg University Hospital  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3236-1225","authenticated-orcid":false,"given":"Luciana\u00a0Kase","family":"Tanno","sequence":"additional","affiliation":[{"name":"University Hospital of Montpellier  Montpellier France"},{"name":"Desbrest Institute of Epidemiology and Public Health University of Montpellier \u2013 INSERM  Montpellier France"},{"name":"WHO Collaborating Centre on Scientific Classification Support  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2197-9767","authenticated-orcid":false,"given":"Victoria","family":"Cardona","sequence":"additional","affiliation":[{"name":"Department of Allergy Hospital Universitari Vall d'Hebron  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3449-1245","authenticated-orcid":false,"given":"Margitta","family":"Worm","sequence":"additional","affiliation":[{"name":"Division of Allergy and Immunology, Department of Dermatology, Venerology and Allergology Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Berlin Institute of Health  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2006-7221","authenticated-orcid":false,"given":"Antoine","family":"Deschildre","sequence":"additional","affiliation":[{"name":"Paediatric Pulmonology and Allergy Department Jeanne de Flandre Hospital, CHU Lille  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5026-5862","authenticated-orcid":false,"given":"Antonella","family":"Muraro","sequence":"additional","affiliation":[{"name":"Food Allergy Referral Centres Padua University Hospital  Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7777-4501","authenticated-orcid":false,"given":"Lene\u00a0H.","family":"Garvey","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergy, Danish Anaesthesia Allergy Centre, Allergy Clinic Copenhagen University Hospital\u2010Herlev and Gentofte  Copenhagen Denmark"},{"name":"Department of Clinical Medicine University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9862-5161","authenticated-orcid":false,"given":"Paul\u00a0J.","family":"Turner","sequence":"additional","affiliation":[{"name":"National Heart &amp; 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