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BACKGROUND: US-based perioperative anaphylaxis (POA) studies are limited to single-center experiences. A recent report found that a serum acute tryptase (sAT) >9.8 ng/mL or mast cell activation (MCA) can predict POA causal agent identification. Urinary mast cell mediator metabolites (uMC) have not been studied in POA.
OBJECTIVE: To analyze the epidemiologic data of POA, to determine if sAT or MCA can predict suspected causal agent identification, and to evaluate uMC utility in POA.
METHODS: This study is a retrospective multicenter review of POA cases that were subcategorized by suspected causal agent identification status. sAT, MCA (defined as sAT >2 + 1.2 × serum baseline tryptase), and uMC (N-methylhistamine [N-MH], 11β-prostaglandin-F2α [11β-PGF2α], leukotriene E4 [LTE4]) were recorded.
RESULTS: Of 100 patients (mean age 52 [standard deviation 17] years, 94% adult, 50% female, 90% White, and 2% Hispanic) with POA, 73% had an sAT available, 41% had MCA, 16% had uMC available, and 50% had an identifiable suspected cause. POA cases with an identifiable suspected cause had a positive MCA status (100% vs 78%; P = .01) compared with POA with an unidentifiable cause. An elevated median sAT did not predict causal agent identification. Positive uMC were not associated with suspected causal agent identification during POA. Patients with positive uMC had a higher median sAT (30 vs 6.45 ng/mL; P = .001) and MCA status (96% vs 12%; P = .001) compared with negative uMC patients. Patients with POA had an elevated acute/baseline uMC ratios: 11β-PGF2α ratio > 1.6, N-MH ratio >1.7, and LTE4 ratio >1.8.
CONCLUSIONS: The presence of MCA in POA is associated with suspected causal agent identification. Positive uMC possibly correlate with a higher sAT level and MCA status but require further study. The authors suggest applying an acute/baseline uMC ratio (11β-PGF2α ratio >1.6, N-MH ratio >1.7, and LTE4 ratio >1.87) in patients with POA for MCA when a tryptase level is inconclusive during POA evaluations.

UNASSIGNED: Paired sampling of acute (aST) and basal (bST) serum tryptase has been recommended when investigating patients with a suspected perioperative hypersensitivity (POH) reaction. In the current consensus formula, an aST value exceeding (1.2×bST+2) confirms mast cell activation. The current consensus formula has been validated in adults but not in children.
UNASSIGNED: We prospectively included 96 children who underwent uneventful anaesthesia and sampled serum tryptase at baseline and 60-90 min after induction. Tryptase changes were then compared with those in 94 children with suspected POH who were retrospectively included from four reference centres in Belgium, France, and Denmark.
UNASSIGNED: We observed a median decrease in serum tryptase during uneventful anaesthesia of 0.41 μg L-1 (-15.9%; P<0.001). The current consensus formula identified mast cell activation in 31.9% of paediatric POH patients. After generating receiver operating characteristic curves through 100 repeated five-fold cross-validation, aST>bST+0.71 was identified as the optimal cut-off point to identify mast cell activation. This new paediatric formula has higher sensitivity than the current consensus formula (53.2% vs 31.9%, P<0.001) with a specificity of 96.9%. Analysis in the subpopulation where a culprit was identified and in grade 3-4 reactions similarly yielded higher sensitivity for the new paediatric formula when compared with the current consensus formula (85.3% vs 61.8%; P=0.008 and 78.0% vs 48.8%; P<0.001, respectively). Internally cross-validated sensitivity and specificity were 53.3% and 93.3%, respectively.
UNASSIGNED: This is the first study suggesting the need for an adjusted formula in children to identify perioperative mast cell activation as tryptase is significantly lowered during uneventful anaesthesia. We propose a new formula (aST>bST+0.71) which performs significantly better than the current consensus formula in our multicentric paediatric population.

BACKGROUND: There are few studies of perioperative hypersensitivity reactions in children. The diagnosis of perioperative hypersensitivity reactions may be under estimated because it is difficult to recognize the reactions. Anaphylaxis may go unnoticed because of patient unconsciousness. Urticaria may be missed due to sterile drapes. The aim of this study was to prospectively evaluate perioperative hypersensitivity reactions.
METHODS: In this prospective study, patients with suspected perioperative hypersensitivity reactions aged 0-18 years who underwent surgery at the Department of Pediatric Surgery, Cerrahpasa Faculty of Medicine, between 2019 and 2021 were investigated. Suspected reactions in the perioperative period were graded according to the Ring and Messmer scale. Patients with suspected reactions were examined 4-6 weeks after the reaction. If necessary, specific IgE and basophil activation tests were performed. Reactions of grades III-IV were considered anaphylaxis. If one test modality was strongly positive and there was a relevant time point or repeated allergic reactions, or at least two test modalities were positive, hypersensitivity was confirmed. In all patients, serum tryptase levels were analyzed at the time of the reaction, 2 h after the reaction, and 4-6 weeks after the reaction as part of the allergic evaluation.
RESULTS: A total of 29 patients (8 female, 21 male) suspected of having an intraoperative reaction during the study were included in the analysis. Perioperative hypersensitivity reactions were noted in 1 patient. The incidence of perioperative hypersensitivity reactions was reported to be 0.03% (n = 1/2861). While anaphylaxis was confirmed in 1 patient, 5 patients were considered possible anaphylaxis cases.
CONCLUSIONS: Perioperative hypersensitivity reactions can be life-threatening and may recur with further administration. Collaboration between pediatric surgeons, anesthesiologists, and allergists can prevent further reactions. All suspected cases should be evaluated by an experienced allergist soon after the initial reaction.

UNASSIGNED: Identify the causative agent of POH, to avoid re-exposure and assess the use of alternative treatment.
UNASSIGNED: 10 cases of immediate POH are described, in all of them a history of previous surgical procedures, carrying out a 3-step protocol: 1st documenting the surgical record to identify exposures, 2nd performing skin and/or epicutaneous tests and 3rd searching for an alternative treatment. treatment if a new surgical procedure is required and in selected cases challenge tests.
UNASSIGNED: Of a total of 10 patients with immediate POH, tests were performed according to the case: neuromuscular blockers, anesthetics, opioids, NSAIDs, anti- biotics, diuretics, latex, isodine, and chlorhexidine; finding positive tests in 7 (70%) patients: in 4 (40%) neuromuscular blockers, one of them also positive for latex, in 2 (20%) anesthetics and finally finding a pharmacological alternative in 2 (2%) and recommending free operating room latex in 2 cases (20%), the rest (30%) were classified as related to the surgical procedure and medication management.
UNASSIGNED: The study of POH is focused on ensuring safety in subsequent exposures, so in addition to identifying the causative agent, the role of the allergist also leads to a search for a safe alternative in patient management.
UNASSIGNED: Identificar agente causal de POH, para evitar reexposición y valorar uso de alternativa de tratamiento.
UNASSIGNED: Se describen 10 casos de POH inmediata, en todos antecedente de procedimientos quirúrgicos previos, realizándose protocolo de 3 pasos: 1°docu- mentar registro quirúrgico para identificar exposiciones, 2° realización de pruebas cutáneas y/o epicutáneas y 3° búsqueda de alternativa de tratamiento en caso de requerir nuevo procedimiento quirúrgico y en casos seleccionados pruebas de reto.
UNASSIGNED: De un total de 10 pacientes con POH inmediata, se realizaron pruebas según el caso: bloqueadores neuromusculares, anestésicos, opioides, AINE, antibióticos, diuréticos, látex, isodine y clorhexidina; encontrando pruebas positivas en 7 pacientes (70%): en 4 (40%) bloqueadores neuromusculares, uno de ellos también positivo para látex, en 2 (20%) anestésicos y finalmente encontrando alternativa farmacológica en 2 (2%) y recomendando quirófano libre de látex en 2 casos (20%), el resto (30%) fueron catalogados como relacionados con procedimiento quirúrgico y manejo de medicamentos.
UNASSIGNED: El estudio de las POH está enfocado en asegurar seguridad en exposiciones posteriores, por lo que además de la identificación de agente causal, el papel del alergólogo también conlleva a una búsqueda de alternativa segura en el manejo del paciente.

Perioperative anaphylaxis is associated with significant morbidity and mortality. Prompt and appropriate treatment is required for optimal outcome. Despite general knowledge of this condition, delays occur in the administration of epinephrine and in particular the use of i.v. route of administration in the perioperative setting. Barriers should be addressed to allow prompt utilisation of i.v. epinephrine in perioperative anaphylaxis.

Perioperative hypersensitivity constitutes an important health issue, with potential dramatic consequences of diagnostic mistakes. However, safe and correct diagnosis is not always straightforward, mainly because of the application of incorrect nomenclature, absence of easy accessible in-vitro/ex-vivo tests and uncertainties associated with the non-irritating skin test concentrations. In this editorial we summarize the time line, seminal findings, and major realizations of 25 years of research on the mechanisms, diagnosis, and management of perioperative hypersensitivity.

Perioperative hypersensitivity (POH) is an uncommon, potentially life-threatening event. Identification of POH can be difficult given the lack of familiarity, physiological effects of anesthesia, draping of the patient during surgery, and potential nonimmunological factors contributing to signs and symptoms. Given the unique nature and large number of medications administered in the perioperative setting, evaluation of POH can be challenging. In this paper, we present a practical approach to management with an emphasis on understanding what happens in the operating room, the overlap of signs and symptoms between nonimmunological and immunological reactions, acute management, and subsequent evaluation. In addition, we provide a strategy for further review of an initially negative evaluation and emphasize the importance of establishing management plans for the patient as well as providing recommendations to the medical, anesthesia, and surgical teams for future surgeries. A critical factor for successful management at all points in the process is a close collaboration between the anesthesia and the allergy teams.

Evaluation of perioperative hypersensitivity (POH) is challenging, and accurate screening tools are needed to optimize the diagnostic process. We aimed to assess and validate the diagnostic value of a published algorithm (using tryptase and clinical presentation) to identify appropriate individuals for further testing for IgE-mediated POH.
We analysed the clinical presentation (tryptase elevation, cardiovascular, respiratory, skin involvement) of patients proceeding to testing for possible IgE-mediated POH at a single tertiary referral centre, relative to subsequent skin testing and specific IgE results. Clinical presentations by drug class were also determined.
In 293 consecutive patients, the use of a published algorithm based on one or more of; (i) defined increase in serum tryptase, (ii) involvement of at least two-organ systems, or (iii) presentation with new urticaria and/or angioedema; was highly sensitive [98.8% (CI95: 95.7-99.9%)] but less specific [34.6% (CI95: 25.7-44.4%)] in identifying patients testing positive on skin testing and/or specific IgE. Presentation with cardiovascular symptoms was also sensitive [89.8%(CI95: 84.2-94.0%)], while the combination of respiratory symptoms and increased tryptase was most specific [85.9%(CI95:76.6-92.5%)]. Respiratory involvement was more common in neuromuscular blocking agent allergy, while urticaria/angioedema was more common in antibiotic allergy.
The published algorithm (of tryptase rise, two-organ involvement or new urticaria/angioedema) is highly sensitive, and appropriate as a screening tool to identify patients suitable for testing for IgE-mediated POH.