Management of Refractory Anaphylaxis: An Overview of Current Guidelines

Abstract

Adrenaline; Anaphylaxis; Vasopressors

Adrenalina; Anafilaxi; Vasopressors

Adrenalina; Anafilaxia; Vasopresores

In this review, we compare different refractory anaphylaxis (RA) management guidelines focusing on cardiovascular involvement and best practice recommendations, discuss postulated pathogenic mechanisms underlining RA and highlight knowledge gaps and research priorities. 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-line vasopressor (noradrenaline, vasopressin, metaraminol and dopamine) is unknown. Most guidelines recommend IV glucagon for patients on beta-blockers, 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-acetyl hydrolase or hereditary alpha-tryptasaemia, 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.

This work has no funding. P.J.T. is supported by the UK Medical Research Council (Grant Ref: MR/W018616/1), and through the NHR Biomedical Research Centre based at Imperial College Healthcare NHS Trust and Imperial College London. For the purpose of open access, the author has applied a Creative Commons Attribution (CC BY) license to any Author Accepted Manuscript version arising. T.E.D. is supported in part by the National Center for Advancing Translational Sciences of the National Institutes of Health, under Award Number UL1TR001425. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.