Molecular mechanisms and pathophysiology of perioperative hypersensitivity and anaphylaxis: a narrative review

Abstract

Perioperative hypersensitivity reactions (POH) constitute a clinical and diagnostic challenge, a consequence of heterogeneous clinical presentations, and multiple underlying pathomechanisms. POH do not necessarily involve an allergen-specific immune response with cross-linking of specific immunoglobulin E (sIgE) antibodies on mast cells and basophils. POH can also result from alternative specific and non-specific effector cell activation/degranulation such as complement-derived anaphylatoxins and off-target occupancy of mast cell, basophil, or both surface receptors. Moreover, POH and anaphylaxis can occur independent from mast cell and basophil degranulation.The manifestations of POH primarily affect the cardiovascular, respiratory, and integumentary systems. POH present within the context of surgical or procedural pathology and the effects of surgical and anaesthetic techniques on pre-existing physiological reserve. The majority of cases of appropriately-treated intraoperative anaphylaxis can be considered a compensated cardiovascular anaphylaxis. With increasing severity of anaphylaxis, maldistribution and hypovolaemia lead to reduced venous return and circulatory failure. Treatment with a combination of epinephrine and i.v. fluid is critical for successful resuscitation, although the excessive use of epinephrine without adequate volume expansion may be deleterious. Neural control of the airways is important in the pathophysiology of bronchospasm. Anticholinergic drug premedication is beneficial in patients with hyperreactive airways. Pulmonary oedema can result from a combination of pulmonary capillary hypertension, incompetence of the alveolocapillary membrane, or both. Angioedema can be distinguished mechanistically into histaminergic and non-histaminergic (e.g. bradykinin-mediated). An understanding of the molecular mechanisms and pathophysiology of POH are essential for the immediate management and subsequent investigation of these cases.

Early Skin Test after Anaphylaxis during Induction of Anesthesia: A Case Report

“…The range of anaphylaxis and perioperative hypersensitivity has been expanded to incorporate non-immune-mediated life-threatening, generalized, and systemic reactions into it [6]. Symptoms of anaphylaxis vary and may include hypotension, tachycardia, cardiovascular collapse, angioedema, bronchospasm, wheezing, hypoxia, pulmonary edema, and urticaria.…”

The use of drug provocation testing in the investigation of suspected immediate perioperative allergic reactions: current status

“…31 In addition, suspected perioperative hypersensitivity can result from various non-allergic processes without specific immune responses such as direct activation of the mast cell via specific receptors or enzymatic interference. 32 These will go undetected by traditional tests, as skin testing and in vitro tests primarily diagnose IgE-mediated reactions.…”

Perfil Epidemiológico das principais drogas e substâncias relacionadas à etiologia da Anafilaxia Perioperatória no Brasil e no Mundo: uma revisão literária / Epidemiological Profile of the main drugs and substances related to the etiology of Perioperative Anaphylaxis in Brazil and in the World: a literary review

“…Posteriormente, esses anticorpos sIgE homocitotrópicos circulantes se ligam aos seus receptores de alta afinidade (FcεRI) presentes na membrana superficial de ambos os tipos de células efetoras. O encontro de um alérgeno específico que interliga os complexos sIgE / FcεRI, presentes na membrana superficial de ambas as células efetoras, induz uma complexa cascata de sinalização a jusante que culmina na degranulação composta com liberação de agregados de grânulos secretores (EBO, DIDIER G et al, 2019). Os mastócitos e basófilos liberam mediadores pré-formados (histamina, triptase e outras proteases), mediadores lipídicos recém-sintetizados (prostaglandina, leucotrienos, fator de ativação plaquetária PAF), geralmente gerando ao longo de minutos e horas as quimiocinas, citocinas e os fatores de crescimento.…”

“…No que concerne às definições terminológicas, o termo hipersensibilidade é atualmente usado como um termo genérico para cobrir todas as reações inesperadas, mas reproduzíveis, à exposição a um substância definida que é tolerada por indivíduos normais, e que vão além das ações farmacológicas primárias (EBO, DIDIER G et al, 2019). Nesse contexto, é importante ressaltar que essa definição não leva em consideração o mecanismo fisiopatológico subjacente, e foi proposto usar os termos hipersensibilidade alérgica e não alérgica para denotar um mecanismo imune ou não imune, respectivamente.…”

“…As reações perioperatórias de hipersensibilidade (RPH) constituem um desafio clínico e diagnóstico como consequência de apresentações clínicas heterogêneas e múltiplos mecanismos subjacentes (EBO, DIDIER G et al, 2019) Os dados epidemiológicos sugerem que a incidência global de anafilaxia induzida por drogas tem aumentado, destacando a necessidade de melhoria nos sistemas de notificação de alergias.…”