Perioperative anaphylaxis management and testing: a quaternary centre audit.

BACKGROUND: Anaphylaxis is a severe, potentially life-threatening generalized or systemic hypersensitivity reaction. Sequential reports have cited anaphylaxis as the most common cause of anaesthesia-related deaths. We undertook an audit at a quaternary centre, examining the management of perioperative anaphylaxis and quality of referrals made to our anaesthesia allergy testing service. METHODS: The data of 41 patients consulted at St Vincent's Hospital Melbourne for perioperative anaphylaxis between 17th of January 2020 and 20th of January 2022 were analysed. Intervention outcomes included total intravenous fluid administered, adrenaline administration, instigation of CPR and the collection and the timing of serum tryptase samples. We also assessed referral quality, provision of institutional allergy alert and time elapsed from the anaphylaxis event to allergy testing. Contemporaneous Australian and New Zealand Anaesthetic Allergy Group (ANZAAG) guidelines were used as the reference standard for most outcomes. RESULTS: Our data reveals compliance of <80% with respect to intravenous fluid administration, referral quality and tryptase sampling, particularly at the 4-h timepoint. CONCLUSION: Surgical leadership and patient advocacy in the post-acute phase would likely facilitate requisite testing and improve the quality of counselling. We recommend institutions adopt a case-by-case review of management compliance with recommendations. Additionally, we advocate for the inclusion of a prompt to the ANZAAG referral form, that encourages the operator to update their patient's institutional allergy alert while awaiting allergy testing.

The exon-skipping oligonucleotide, KitStop, depletes tissue-resident mast cells in vivo to ameliorate anaphylaxis.

Introduction: Anaphylaxis represents the most extreme and life-threatening form of allergic disease and is considered a medical emergency requiring immediate intervention. Additionally, some people with mastocytosis experience recurrent episodes of anaphylaxis during normal daily activities without exposure to known triggers. While acute therapy consists primarily of epinephrine and supportive care, chronic therapy relies mostly on desensitization and immunotherapy against the offending allergen, which is a time-consuming and sometimes unsuccessful process. These treatments also necessitate identification of the triggering allergen which is not always possible, and thus highlighting a need for alternative treatments for mast cell-mediated diseases. Methods: The exon-skipping oligonucleotide KitStop was administered to mice intradermally, intraperitoneally, or systemically at a dose of 12.5 mg/kg. Local mast cell numbers were enumerated via peritoneal lavage or skin histology, and passive systemic anaphylaxis was induced to evaluate KitStop's global systemic effect. A complete blood count and biochemistry panel were performed to assess the risk of acute toxicity following KitStop administration. Results: Here, we report the use of an exon-skipping oligonucleotide, which we have previously termed KitStop, to safely reduce the severity and duration of the anaphylactic response via mast cell depopulation in tissues. KitStop administration results in the integration of a premature stop codon within the mRNA transcript of the KIT receptor-a receptor tyrosine kinase found primarily on mast cells and whose gain-of-function mutation can lead to systemic mastocytosis. Following either local or systemic KitStop treatment, mice had significantly reduced mast cell numbers in the skin and peritoneum. In addition, KitStop-treated mice experienced a significantly diminished anaphylactic response using a model of passive systemic anaphylaxis when compared with control mice. Discussion: KitStop treatment results in a significant reduction in systemic mast cell responses, thus offering the potential to serve as a powerful additional treatment modality for patients that suffer from anaphylaxis.

Incidence and outcome of anaphylaxis in cardiac surgical patients.

Introduction: Anaphylaxis is a rare but serious and potentially fatal complication of anesthesia. Little is known about the incidence and outcome of anaphylaxis in cardiac surgical patients, which we aimed to investigate. Methods: This was a 21-year retrospective study of cardiac surgical patients at Manchester Royal Infirmary, Manchester Foundation Trust, Manchester, UK. Results: A total of 19 cases of anaphylaxis were reported among 17,589 patients (0.108%) undergoing cardiac surgery. The majority (15/19) occurred before cardiopulmonary bypass (CPB), mostly during or within 30 min after the induction of anesthesia (10/19). Two occurred within 15 min of going onto CPB. Of these 17 cases, 11 were abandoned, and 6 proceeded. The severity of reactions in the patients who proceeded ranged from grade II to grade IV of the Ring and Messmer classification. Two cases occurred after the completion of surgery. All patients survived to 90 days. However, this did not appear to be related to CPB or protamine as most of the reactions occurred before CPB. Instead, the most common causative agents were gelofusine, antibiotics, muscle relaxants, and chlorhexidine. In 6 cases, surgery proceeded despite the anaphylaxis, in 11 cases the surgery was postponed, and in 2 cases the procedure had already been completed. Conclusion: As all patients survived, our results provide preliminary support for proceeding with surgery although we cannot speculate on the likely outcomes of patients who were postponed, had their surgery proceeded. Based on our data, the incidence of anaphylaxis in cardiac surgical patients may be 10-20 times higher than in the general surgical population.

Mast Cell Activation Syndromes: Collegium Internationale Allergologicum Update 2022.

Mast cell activation syndromes (MCASs) are defined by systemic severe and recurrent mast cell activation, usually in form of anaphylaxis, a substantial, event-related increase of the serum tryptase level beyond the individual's baseline and a response of the symptomatology to drugs directed against mast cells, mast cell-derived mediators, or mediator effects. A number of predisposing genetic conditions, underlying allergic and other hypersensitivity states, and related comorbidities can contribute to the clinical manifestation of MCASs. These conditions include hereditary alpha tryptasemia, mastocytosis with an expansion of clonal KIT-mutated mast cells, atopic diathesis, and overt IgE-dependent and IgE-independent allergies. Several of these conditions have overlapping definitions and diagnostic criteria and may also develop concomitantly in the same patient. However, although criteria and clinical features overlap, each of these conditions is characterized by a unique constellation of variables and diagnostic criteria. Since two, three, or more conditions can coexist in the same patient, with obvious clinical implications, it is of crucial importance to diagnose the variant of MCAS precisely and to take all accompanying, underlying and potentially complicating conditions, and comorbidities into account when establishing the management plan. Indeed, most of these patients require multidisciplinary investigations and only a personalized treatment approach can lead to an optimal management plan providing an optimal quality of life and low risk of anaphylaxis.

Life-Threatening Non-Allergic Drug Hypersensitivity Reaction as a Very Rare Side Effect of Rivaroxaban Administration in the Netherlands.

BACKGROUND: Anticoagulant therapy is indicated for the prevention and treatment of thromboembolic disease. Direct oral anticoagulants (DOACs) are frequently prescribed and Rivaroxaban is the most frequently administered DOAC in the Netherlands. Most side effects relate to hemorrhagic complications, however, also non-hemorrhagic side effect may be potentially life threatening. CASE PRESENTATION: A 74-year-old man presented at the emergency department with a ruptured infrarenal abdominal aortic aneurysm for which open aneurysm repair was performed. Postoperatively, the patient developed neurological deficit, respiratory and circulatory failure following rivaroxaban administration, initiated for atrial fibrillation. Even though, the clinical signs resembled an anaphylactic reaction, the skin-prick test was negative and complications most likely resulted from a non-allergic drug hypersensitivity reaction. CONCLUSION: This case report shows that non-allergic drug hypersensitivity reactions may mimic an anaphylactic reaction and can be potentially life threatening. In addition, severe non-hemorrhagic complications after rivaroxaban administration do occur and should be considered in case of acute clinical deterioration.

Idiopathic Anaphylaxis: a Perplexing Diagnostic Challenge for Allergists.

PURPOSE OF REVIEW: The aim of this systematic review is to present the proposed theories of pathogenesis for idiopathic anaphylaxis (IA), to discuss its classification, its diagnostic approach, and management. RECENT FINDINGS: IA represents a major diagnostic challenge and is diagnosed when excluding the possible identifiable triggers of anaphylaxis. The current research, however, revealed that certain conditions including mastocytosis, mast cell activation syndromes, and hereditary alpha tryptasemia can masquerade and overlap with its symptomatology. Also, newly identified galactose-alpha-1,3-galactose mammalian red meat allergy has recently been recognized as underlying cause of anaphylaxis in some cases that were previously considered as IA. IA comprises a heterogenous group of conditions where, in some cases, inherently dysfunctional mast cells play a role in pathogenesis. The standard trigger avoidance strategies are ineffective, and episodes are unpredictable. Therefore, prompt recognition and treatment as well as prophylaxis are critical. The patients should always carry an epinephrine autoinjector.

Time Course and Management of Protracted Anaphylaxis Due to PEG-Asparaginase.

Polyethylene glycosylated (PEG)-asparaginase is a cornerstone of treatment for acute lymphoblastic leukemia (ALL), and effective administration is associated with better outcomes. PEG-asparaginase is associated with a uniphasic hypersensitivity reaction in ∼10% to 20% of patients. We present a 17-year-old male individual diagnosed with very high-risk pre-B-ALL, who experienced protracted anaphylaxis 1 hour following administration of his second PEG-asparaginase dose. This type of allergic reaction has yet to be described in ALL patients treated with PEG-asparaginase. Here, we outline the time course and successful management of protracted anaphylaxis in an ALL patient.

Rapid desensitization to brentuximab vedotin after severe anaphylaxis in the treatment of refractory Hodgkin's lymphoma.

INTRODUCTION: Brentuximab vedotin is a monoclonal antibody drug conjugate used for the treatment of patients with Hodgkin lymphoma. Hypersensitivity reactions to brentuximab vedotin may include cutaneous, cardiovascular, respiratory, gastrointestinal and neurological signs and symptoms. CASE REPORT: We present the case of a 23-year-old Mexican female with stage IV progressive classical nodular sclerosing Hodgkin lymphoma who received multiple previous chemotherapy regimens. Brentuximab vedotin at 1.8 mg/kg (180 mg total dose), for 21-day cycles was indicated. Within 5 min of infusion of the 5th cycle of brentuximab, she developed severe anaphylaxis (hives, angioedema, diaphoresis, tachycardia, dyspnea, hypoxemia and loss of consciousness), which was successfully controlled with epinephrine, steroids and antihistamines.Management and outcome: Intradermal skin test at a concentration of 0.1 mg/ml was positive. Due to the severity of the symptoms and the lack of access to alternative treatments, we performed a desensitization protocol. A total of 180 mg of brentuximab was given in three bag solutions in 12 steps, with an initial concentration dose of 1/100 of the total dose in a course of 5.56 h with no hypersensitivity reactions. DISCUSSION: Severe anaphylaxis has been reported in 1.2% of patients receiving brentuximab vedotin. Patients who are treated by rapid drug desensitization with their first option therapy present a favorable survival rate with better cost-effectiveness in comparison to second-line treatment.

Anafilaxia y anafiláctico / Anaphilactic shock and anaphilaxis

Anaphylaxis is a life-threatening clinical condition that results from the activation of mast cells/basophils, inflammatory pathways, or both. It can be specific (allergic), or non-specific (non-allergic). Most anaphylaxis are mediated by IgE, but there are also some mediated by IgM and complement activation. Incidence is about 1:10,000 anesthesia. Recent studies show that the drugs or substances mostly implicated in producing perioperative anaphylaxis are: neuromuscular blockers (60.6%), antibiotics (18.2%), patent blue dye (5.4%) and latex (5.2%). However, all drugs and substances used during anesthesia and surgery, perhaps with the sole exception of inhalation agents and crystalloids, have been reported as potentially causes of anaphylaxis. The clinical presentation is multisystemic, producing signs and symptoms mainly on skin, respiratory, cardiovascular, gastrointestinal and central nervous systems. In its advanced phase, it may evolve to anaphylactic shock, causing tissue hypoperfusion and leading to altered cell integrity and multiple organ failure, associated with high mortality. Diagnosis is based on clinical presentation (history and clinical manifestations), biological evidence (serum tryptase levels, serum histamine levels and search for specific IgE) and allergological evidence (skin tests, provocation test, mediator release tests and tests of activation of basophils). Treatment include 3 stages: general measures, first-line or primary treatment and second-line or secondary treatment. General measures consist of: Trendelenburg position, invasive monitoring (according to the severity of the clinical presentation), 100% oxygen administration, discontinuation of drugs and/or suspected agents and asking for help. The primary treatment is epinephrine in doses proportional to the clinical manifestations, airway support, 100% oxygen and aggressive resuscitation with intravenous fluids. Secondary treatment includesadministration of bronchialodilators, corticosteroids, and antihistamines.

Una anafilaxia es una condición clínica potencialmente mortal que resulta de la activación específica (alérgica), o no específica (no alérgica) de mastocitos/ basófilos, vías inflamatorias o ambos. La mayoría de las anafilaxias son mediadas por IgE, pero también las hay por IgM y activación del complemento. Su incidencia es de 1:10.000 anestesias. En los últimos estudios, los fármacos o sustancias más implicadas en producir anafilaxia perioperatoria son los bloqueadores neuromusculares (60,6%), los antibióticos (18,2%), las tinturas azules (5,4%) y el látex (5,2%), sin embargo, todas las drogas y sustancias usadas durante la anestesia y la cirugía, tal vez con la única excepción de los agentes inhalatorios y los cristaloides, han sido reportadas como potencialmente causantes de anafilaxia. El cuadro clínico es multisistémico, originando signos y síntomas centrados en la piel y los sistemas respiratorio, cardiovascular, gastrointestinal y nervioso central. En su fase avanzada puede evolucionar a anafiláctico, causando hipoperfusión tisular y llevando a alteración en la integridad celular y falla de múltiples órganos, con alta mortalidad asociada. El diagnóstico se basa en evidencias clínicas (historia y manifestaciones clínicas), evidencias biológicas (niveles de triptasa sérica, de histamina sérica y búsqueda de IgE específicas) y evidencias alergológicas (pruebas cutáneas, test de provocación, pruebas de liberación de mediadores y pruebas de activación de basófilos. El tratamiento incluye 3 etapas: medidas generales, tratamiento de primera línea o primario y tratamiento de segunda línea o secundario. Las medidas generales consisten en poner al paciente en posición de Trendelemburg, iniciar monitorización invasiva según la intensidad del cuadro clínico, administración de oxígeno al 100%, discontinuación de drogas y/o agentes posiblemente incriminados y pedir ayuda. El tratamiento primario es la adrenalina, en dosis proporcionales a las manifestaciones clínicas, el soporte de la vía aérea manteniendo el oxígeno ql 100% y la reanimación agresiva con fluidos endovenosos. El tratamiento secundario incluye la administración de broncodilatadores, corticoesteroides y antihistamínicos.

Severe anaphylactic shock after anesthesia induction: An unusual initial manifestation of Churg-Strauss syndrome.

Churg-Strauss syndrome or eosinophilic granulomatosis with polyangiitits (EGPA) is a rare multisystem disorder. A case of anaphylactic shock after induction of anesthesia, as the initial clinical presentation of Churg-Strauss syndrome in a 15-year-old girl is reported. It is extremely rare to see pediatric patients with previous perioperative anaphylaxis receiving future anesthesia; a multidisciplinary approach including allergist, rheumatologist, anesthesiologist, and surgeon is necessary in order to provide a better future anesthetic plan.

[Anaphylaxis due to a ruptured hydatid cyst]. / Anaphylaxie bei rupturierter Echinokokkuszyste.

HISTORY AND CLINICAL FINDINGS: We report the case of a 27-year-old Syrian patient who came to the emergency department with a syncopal episode. No medical history could be raised due to a language barrier and so the clinical presentation was leading. INVESTIGATIONS AND DIAGNOSIS: The patient exhibited signs of shock, accompanied by an exanthema as well as perioral hematin. In an ultrasound sonography free intraabdominal fluid and an obscure change in the upper abdomen could be visualized. An esophagogastroduodenoscopy showed evidence of an ulcer, however did not explain all symptoms. In a CT abdomen, signs of a ruptured cyst could be demonstrated. TREATMENT AND COURSE: The patient stabilized under the treatment protocol for anaphylaxis. Due to the clinical course and country of origin the patient received albendazole and a partial liver resection for a suspected echinococcus cyst. CONCLUSION: Obscure clinical symptoms alongside signs of shock, should always considered to be an allergic reaction in absence of sepsis or hemorrhage. In anaphylaxis, echinococcosis should always be included in the differential diagnosis.

[Management of perioperative anaphylaxis]. / Management der Anaphylaxie im OP.

The term anaphylaxis describes a severe, potentially life-threatening allergic reaction. It is caused by an acute, systemic immune response to substances against which in most cases a previous sensitization has taken place. An anaphylactic reaction can affect every organ system of the human body. The first signs of an allergic shock are symptoms such as hypotension, tachycardia, exanthema and dyspnea. The complete expression of anaphylactic shock can occur very quickly. A perioperative anaphylaxis, in particular, is not always easy to recognize. Therefore, it is important to know the possible perioperative triggers of anaphylaxis, for instance neuromuscular blocking agents and antibiotics. The treatment has to be initiated quickly to save the life of the patient. The rapid injection of epinephrine and intravenous fluid administration are most important.

Kounis Syndrome after Angioplasty of the Superficial Femoral Artery with Paclitaxel-Coated Balloon.

Drug-coated balloons are used widely as a form of endovascular treatment for peripheral arterial disease, to improve patency by reducing neointimal hyperplasia and restenosis. We present a rare case of acute coronary syndrome secondary to anaphylaxis after inflation of a paclitaxel-coated balloon used to treat a recurrent superficial femoral artery stenosis.

Protamine Induced Anaphylactic Shock after Peripheral Vascular Surgery.

Anaphylactic reactions to protamine are quite rare and almost exclusively reported during cardiac surgery. In this report, we illustrate a rare case of protamine reaction after peripheral vascular surgery a couple of months after cardiac surgery and how the patient survived this critical complication.

Mast cell disorders and idiopathic anaphylaxis: Evaluation and management.

Background: Our understanding of mast cell activation disorders continues to grow, and our management of these syndromes is improving with this increase in knowledge. Despite these advances, there remain some areas of confusion. Conclusion: In this article, we discussed these areas and offered thoughts about establishing the diagnosis and management.