Anaphylaxis in practice: A guide to the 2023 Practice Parameter Update.

This review will summarize new research developments and clinical practice recommendations for the diagnosis and management of anaphylaxis presented in the Joint Task Force on Practice Parameters' 2023 Anaphylaxis Practice Parameter Update. It is intended to serve as a high-level summary of the 2023 practice parameter, which makes clinically impactful recommendations based on new evidence that has emerged since the 2015 practice parameter. We invite clinicians to explore the full 2023 practice parameter to better understand the research methods and underlying evidence that have informed the recommendations summarized here. There are new and evolving diagnostic criteria for anaphylaxis, rules for defining elevated tryptase levels, and recognition of signs and symptoms particular to infants and toddlers. The administration of epinephrine should not be used as a surrogate to diagnose anaphylaxis. Risk factors for anaphylaxis should be assessed on a case-by-case basis. Patient counseling and shared decision making (SDM) are essential for supporting patients' treatment decisions and capacity to manage the risk of anaphylaxis at home and in other community settings. Activation of emergency medical services following home epinephrine administration may not be required in all cases, and patients should be engaged in SDM to determine when home management may be appropriate.

Comparison of the diagnostic performance of tryptase and histamine for perioperative anaphylaxis: A multicenter prospective study.

BACKGROUND: Diagnosing perioperative anaphylaxis (POA) is often challenging. Although a guideline recommends measuring tryptase rather than histamine, there is little evidence for this. We aimed to examine the diagnostic performance and appropriate timing of tryptase and histamine measurements for diagnosing anaphylaxis, and the association between Hypersensitivity Clinical Scoring Scheme (HCSS) scores and elevated biomarkers. METHODS: We measured tryptase and histamine levels thrice: 30 min, 2 h, and at least 24 h after an anaphylactic event for patients with suspected anaphylaxis, and at the induction of general anesthesia and 30 min and 2 h after the start of surgery for control patients without a reaction. Absolute values and the magnitude and rate of change from baseline were evaluated. We determined the thresholds of tryptase and histamine levels with the best diagnostic performance and compared their performance. RESULTS: Forty-five patients with perioperative anaphylaxis were included in this study. The control group included 30 patients with uneventful general anesthesia and 12 patients with a suspected but unconfirmed diagnosis of perioperative anaphylaxis. Comparison at the same measurement timings showed that tryptase generally had better diagnostic performance than histamine. Both showed better diagnostic performance when assessed using multiple measurements rather than a single measurement. The best diagnostic performance was seen with the percentage change in the higher tryptase value, whether measured at 30 min or 2 h after anaphylaxis onset, as compared to baseline. However, neither tryptase nor histamine levels correlated with HCSS scores. CONCLUSIONS: Overall, tryptase showed better diagnostic performance than histamine. When multiple tryptase measurements are possible, parameters calculated using two acute phase measurements and the baseline level have better diagnostic performance.

A US-Based Multicenter Retrospective Report of Perioperative Anaphylaxis, 2010-2021.

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], 11ß-prostaglandin-F2α [11ß-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: 11ß-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 (11ß-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.

Australian and New Zealand Anaesthetic Allergy Group/Australian and New Zealand College of Anaesthetists perioperative anaphylaxis management guideline 2022.

Perioperative anaphylaxis is a potentially life-threatening emergency that requires prompt recognition and institution of life-saving therapy. The Australian and New Zealand College of Anaesthetists and Australian and New Zealand Anaesthetic Allergy Group have partnered to develop the anaphylaxis management guideline along with crisis management cards that are recommended for use in suspected anaphylaxis in the perioperative setting. This is the third version of these guidelines with the second version having been published in 2016. This article contains the revised Australian and New Zealand Anaesthetic Allergy Group/Australian and New Zealand College of Anaesthetists perioperative anaphylaxis management guideline, with a brief review of the current evidence for the management of anaphylaxis in the perioperative environment.

A nurse-driven penicillin allergy risk score in the preoperative setting was associated with increased cefazolin use perioperatively.

STUDY OBJECTIVE: To characterize and assess the effects of a preoperative, nurse-driven penicillin allergy risk stratification tool on rates of perioperative cefazolin and second-line antibiotic use. DESIGN: Quasi-experimental quality improvement study of penicillin-allergic surgical patients undergoing procedures for which cefazolin is indicated. SETTING: Outpatient Perioperative Care Clinic (PCC) for preoperative surgical patients at a tertiary care center. PATIENTS: 670 and 1371 adult penicillin-allergic PCC attendants and non-attendants, respectively. INTERVENTION: A paper penicillin allergy risk stratification questionnaire was administered during the PCC visit. Nurses were educated on its use. MEASUREMENTS: Antibiotic (cefazolin, clindamycin, vancomycin) use rates in the 24 months before and 17 months after intervention implementation in November 2020 (November 2018 - April 2022) were assessed in penicillin-allergic PCC attendants with statistical process control charts. Multivariable logistic regression assessed antibiotic use rates pre- and post-intervention adjusting for age, sex, surgical specialty and penicillin allergy history severity. Similar analyses were done in penicillin-allergic PCC non-attendants. MAIN RESULTS: Of 670 penicillin-allergic PCC attendants, 451 (median [IQR] age, 66 (Sousa-Pinto et al., 2021 [14])) were analyzed pre-intervention and 219 (median [IQR] age, 66 (Mine et al., 1970 [13])) post-intervention. One month after implementation, process measures demonstrated an upward shift in cefazolin use for PCC attendants versus no shift or other special cause variation for PCC non-attendants. There were increased odds of cefazolin use (aOR 1.67, 95% CI [1.09-2.57], P = 0.019), decreased odds of clindamycin use (aOR 0.61, 95% CI [0.42-0.89], P = 0.010) and decreased odds of vancomycin use (aOR 0.56, 95% CI [0.35-0.88], P = 0.013) in PCC attendants post-intervention. This effect did not occur in PCC non-attendants. There was no increase in perioperative anaphylaxis post-intervention. CONCLUSIONS: A simple penicillin allergy risk stratification tool implemented in the preoperative setting was associated with increased use of cefazolin and decreased rates of second-line agents post implementation.

Epidemiology of perioperative anaphylaxis in France in 2017-2018: the 11th GERAP survey.

BACKGROUND: Perioperative anaphylaxis is rare but is associated with significant morbidity. This complication has been well described in France by the GERAP (Groupe d'Etude des Réactions Anaphylactiques Périopératoires), a network focused on its study. The epidemiology of perioperative anaphylaxis is evolving, influenced by environmental factors and clinical practice. The aim of this study was to update the epidemiology of perioperative anaphylaxis in France. METHODS: This multicentre retrospective study was performed in 26 allergy clinics of the GERAP network in 2017-8. RESULTS: There were 765 patients with perioperative anaphylaxis included. Most cases were severe, with 428 (56%) reactions graded as 3 or 4 according to the Ring and Messmer classification. Skin test results were available for 676 patients, with a culprit agent identified in 471 cases (70%). Neuromuscular blocking agents were the main cause of perioperative anaphylaxis (n=281; 60%), followed by antibiotics (n=118; 25%) and patent blue dye (n=11; 2%). Cefazolin was the main antibiotic responsible for perioperative anaphylaxis (52% of antibiotic-related reactions). Suxamethonium and rocuronium were the main neuromuscular blocking agents responsible for perioperative anaphylaxis with 7.1 (6.1-8.4) and 5.6 (4.2-7.4) reactions per 100,000 vials sold, respectively, whereas cefazolin-related cases were estimated at 0.7 (0.5-0.9) reactions per 100,000 vials sold. CONCLUSIONS: Our results confirm that most commonly identified triggering agents remain neuromuscular blocking agents. Reactions to antibiotics, particularly cefazolin, are becoming increasingly frequent. The origin of sensitisation to cefazolin is unknown, as no cross-sensitisation has been described, and it should be the subject of further study. Perioperative anaphylaxis should be followed over the years and understood given the changing triggers. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT04654923).

Relationship between perioperative anaphylaxis and history of allergies or allergic diseases: A systematic review and meta-analysis with meta-regression.

STUDY OBJECTIVE: We conducted this meta-analysis to summarize the available evidence and evaluate the relationship between a history of allergies/allergic diseases and perioperative anaphylaxis to offer preventive decision support. DESIGN: Systematic review and meta-analysis of observational studies. SETTING: We searched the MEDLINE (OVID), EMBASE, and the Cochrane Central Register of Controlled Trials databases for observational studies. Two investigators independently performed the search, screened the articles, and collected the study details. MEASUREMENTS: Several databases were systematically searched to evaluate the relationship between a history of allergies/allergic diseases and perioperative anaphylaxis using subgroup analysis, sensitivity analysis and meta-regression. MAIN RESULTS: A total of 19 studies involving 672 anaphylaxis episodes, 5608 immune-mediated reactions, and 1126 severe episodes met the eligibility criteria and were included in this meta-analysis. Drug allergies, food allergies, a history of allergies, and atopy increased the incidence of perioperative anaphylaxis (Drug allergies, odds ratio [OR] 3.54, 95% confidence interval [CI] 1.07-11.69; Food allergies, OR 2.29, 95% CI 1.23-4.26; A history of allergies, OR 4.86, 95% CI 3.65-6.49; Atopy, OR 3.58, 95% CI 1.47-8.71), but not the presence of immune-mediated reactions and the severity of perioperative anaphylaxis. CONCLUSIONS: Patients with previous drug allergies, food allergies, a history of allergies, or atopy are more likely to develop anaphylaxis during the perioperative period. Additional studies should be carried out to determine whether a history of allergies/allergic diseases is a major factor for perioperative anaphylaxis when confounders are controlled.

Examining cefazolin utilization and perioperative anaphylaxis in patients with and without a penicillin allergy label: A cross-sectional study.

STUDY OBJECTIVE: To compare the occurrence of cefazolin perioperative anaphylaxis (POA) in patients with and without a penicillin allergy label (PAL) to determine whether the prevalence of cefazolin POA differs based on the presence of a PAL. DESIGN: Cross-sectional study. SETTING: A large U.S. healthcare system in the Baltimore-D.C. region, July 2017 to July 2020. PATIENTS: 112,817 surgical encounters across inpatient and outpatient settings in various specialties, involving 90,089 patients. Of these, 4876 (4.3%) encounters had a PAL. INTERVENTIONS: Perioperative cefazolin administration within 4 h before surgery to 4 h after the procedure began. MEASUREMENTS: The primary outcome was cefazolin POA in patients with and without PALs. Potential POA cases were identified based on tryptase orders or diphenhydramine administrations within the initial cefazolin administration to 6 h postoperatively. Verification included two validation steps. The first checked for hypersensitivity reaction (HSR) documentation, and the second, led by Allergy specialists, identified POA and the probable culprit. The secondary outcome looked at cefazolin use trends in patients with a PAL, stratified by setting and specialty. MAIN RESULTS: Of 112,817 encounters, 1421 (1.3%) had possible cefazolin HSRs. Of these, 22 (1.5%) had POA, resulting in a 0.02% prevalence. Of these, 13 (59.1%) were linked to cefazolin and 9 (40.9%) attributed to other drugs. Only one cefazolin POA case had a PAL, indicating no significant difference in cefazolin POA prevalence between patients with and without PALs (p = 0.437). Perioperative cefazolin use in patients with PALs steadily increased from 2.6% to 6.0% between 2017 and 2020, specifically in academic settings. CONCLUSIONS: The prevalence of cefazolin POA does not exhibit significant differences between patients with and without PALs, and notably, the incidence remains remarkably low. Based on these findings, it is advisable to view cefazolin as an acceptable choice for prophylaxis in patients carrying a PAL.

Paediatric perioperative hypersensitivity: the performance of the current consensus formula and the effect of uneventful anaesthesia on serum tryptase.

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Clinical variables and genetic variants associated with perioperative anaphylaxis in Chinese Han population: A pilot study.

Background: Perioperative anaphylaxis (POA) can lead to severe consequences. Identifying clinical risk factors and genetic loci associated with POA through pre-prescription screening may help reduce its incidence. Methods: Using univariate regression and covariate-adjusted multivariate regression, we retrospectively analyzed the association between clinical characteristics and POA in 72 POA patients and 72 non-POA individuals. The discovery study of whole-exome association relied on whole-exome sequencing of 73 POA cases and 1339 healthy individuals. A replication study involving an independent set of 16 POA cases and 1339 healthy individuals confirmed this association. The accurate typing of human leucocyte antigen through exome sequencing (ATHLATES) algorithm and the whole-exome sequencing data were used for genotyping the human leucocyte antigen G (HLA-G) of 73 POA patients. The HLA-G of 16 POA cases and 122 non-POA patients were genotyped through Sanger sequencing. We used Fisher's exact probability method to compare the allele and carrier frequencies between POA patients and healthy individuals or non-POA patients. A Pc (P/Bonferroni correction coefficient) < 0.05 represents statistical significance. Results: Regression analysis identified female sex, an unconfirmed food allergy label, and a history of prior surgery as clinical variables associated with POA. The whole-exome association discovery study identified a strong signal in the major histocompatibility complex region on chromosome 6, with the rs1130356 being the most significant locus (P = 1.5E-10, OR = 3.4, 95% CI = 2.4-4.9). The replication study verified the association between the rs1130356-T allele and POA cases (P = 1.0E-6, OR = 6.3, 95% CI = 3.1-12.7). Compared with non-POA patients, HLA-G∗01:01 (Pc = 2.4E-4, OR = 2.4, 95% CI = 1.6-3.6) was significantly enriched, while HLA-G∗01:04 (Pc = 1.2E-6, OR = 0.3, 95% CI = 0.2-0.5) was lessened in POA patients. Conclusion: Our study suggested an association between POA and the risk factors of female sex, an unconfirmed food allergy label, and prior surgery. HLA-G, located in the human leucocyte antigen (HLA) region, may act as a surrogate genetic marker for POA. This suggests a causal relationship between this specific genomic region and POA. Our findings shed light on the contribution of human exome genetic variants to the susceptibility to POA.

Challenges in Drug and Hymenoptera Venom Hypersensitivity Diagnosis and Management in Mastocytosis.

Mastocytosis is a myeloproliferative neoplasm characterized by abnormal proliferation and activation of clonal mast cells typically bearing the KITD816V mutation. Symptoms manifest due to the release of bioactive mediators and the tissue infiltration by neoplastic mast cells. Mast cell activation symptoms include flushing, pruritus, urticaria, abdominal cramping, diarrhea, wheezing, neuropsychiatric symptoms, and anaphylaxis. Up to 50% of patients with mastocytosis report a history of provoked and unprovoked anaphylaxis, with Hymenoptera venom and drugs the most common culprits. NSAIDs, antibiotics, vaccines, perioperative medications, and radiocontrast media are often empirically avoided without evidence of reactions, depriving patients of needed medications and placing them at risk for unfavorable outcomes. The purpose of this review is to highlight the most common agents responsible for adverse drug reactions in patients with mastocytosis, with a review of current epidemiology, diagnosis, and management of drug hypersensitivity and Hymenoptera venom allergy.

Remimazolam Anaphylaxis during Induction of General Anesthesia Confirmed by Provocation Test-A Case Report and Literature Review.

Background: Remimazolam besylate, a newly developed drug, is linked to various anaphylaxis cases. We present a case of remimazolam anaphylaxis confirmed using a provocation test. Case: A 51-year-old female patient was scheduled for humeral pinning. General anesthesia was induced using remimazolam, rocuronium, and remifentanil. After tracheal intubation, the patient experienced decreased blood pressure, increased heart rate, and a systemic rash. Epinephrine was administered repeatedly, and the patient's vital signs stabilized. Acute phase tryptase levels were within normal limits. After four weeks, intradermal test results were negative. When remimazolam was administered intravenously for the provocation test, facial swelling, flushing, and coughing occurred, which improved with epinephrine. The culprit drug was identified as remimazolam using a provocation test. Conclusions: When anaphylaxis occurs during anesthesia induction, remimazolam should not be ruled out as the causative drug. If the skin test result for remimazolam is negative, a provocation test should be considered. The provocation test should be initiated cautiously at a low dose under careful patient monitoring.

Drug and Venom Allergy in Mastocytosis.

Patients with mastocytosis have an increased risk for mast cell activation events including anaphylaxis when exposed to certain drugs and Hymenoptera venom. Hypotension and cardiovascular collapse without skin or other systemic manifestations can occur after Hymenoptera stings, during the perioperative period, and after exposure to nonsteroidal ntiinflammatory drugs, opioids, and other mast cell activating medications, including vancomycin and quinolones. This chapter reviews the epidemiology, mechanisms, diagnosis, management, and treatment options for Hymenoptera venom and drug-induced reactions in patients with mastocytosis.

Suspected perioperative anaphylaxis: are we making the correct diagnosis?

We provide a commentary on aspects of a prospective study of the epidemiology of perioperative anaphylaxis in Japan (Japanese Epidemiologic Study for Perioperative Anaphylaxis [JESPA]). Accurate diagnosis of perioperative anaphylaxis is important for research but essential for clinical safety. We evaluate the diagnostic approach used in the JESPA study and caution against over-reliance on diagnostic tests that lack sensitivity and specificity when clinical data suggest an immediate perioperative hypersensitivity reaction is likely.

Treatment of perioperative anaphylaxis: room for improvement?

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.

Management of Suspected Life-Threatening Perioperative Anaphylaxis and Risk Factors for Near-Fatal and Fatal Outcomes: A Retrospective Study in China.

Purpose: Perioperative anaphylaxis (POA) is an acute severe systemic hypersensitivity reaction characterized by life-threatening respiratory and circulatory collapse. In our previous study, we reported the epidemiology of suspected POA in China. In the present study, we aimed to elucidate the management and outcomes of these cases and further verify the risk factors for near-fatal and fatal outcomes. Patients and Methods: This was a retrospective study of 447 cases of suspected life-threatening POA encountered at 112 tertiary hospitals in mainland China between September 2018 and August 2019. Patient characteristics, symptoms, duration of hypotension, treatments, and clinical outcomes were documented. Bivariate logistic regression was used to identify risk factors for near-fatal and fatal outcomes. Results: Most cases of suspected POA (89.9%) were recognized and treated within 5 min. Epinephrine was administered as the initial treatment in 232 (51.9%) cases. Corticosteroids (26.6%), other vasoactive drugs (18.3%), and bronchodilators (1.6%) were also administered as the initial treatment instead of epinephrine. The initial dosage of epinephrine (median, 35 µg) was insufficient according to the anaphylaxis guidelines. On multivariable analysis, age ≥65 years (odds ratio [OR] 7.48; 95% confidence interval [CI]: 1.33-41.87, P=0.022), ASA physical status IV (OR 17.68; 95% CI: 4.53-68.94; P<0.001), and hypotension duration ≥15 min (OR 3.63; 95% CI: 1.11-11.87; P=0.033) were risk factors for fatal and near-fatal outcomes. Conclusion: Most cases in this study were managed in a timely manner, but the epinephrine application should be optimized according to the guidelines. Age ≥65 years, ASA physical status IV, and long-term hypotension were risk factors for near-fatal and fatal outcomes.

Pholcodine, perioperative anaphylaxis, and the European Medicines Agency: finally the decision to remove pholcodine from the market in the European Union.

Two recent case-control studies, both published in the British Journal of Anaesthesia, have shown that intake of pholcodine-containing cough medicines during the year preceding general anaesthesia significantly increased the risk of anaphylaxis caused by neuromuscular blocking agents. Both a French multicentre study and a single-centre study from Western Australia offer strong support to the pholcodine hypothesis for IgE-sensitisation to neuromuscular blocking agents. The European Medicines Agency, criticised for not taking preventive action at its first assessment of pholcodine in 2011, finally recommended a stop to sales of all pholcodine-containing medicines throughout the EU on December 1, 2022. Time will tell whether this reduces the incidence of perioperative anaphylaxis in the EU, as in Scandinavia.

Investigating the optimal diagnostic value of histamine for diagnosing perioperative hypersensitivity: a prospective, observational study.

Although several guidelines recommend measuring blood tryptase and histamine concentrations to diagnose perioperative anaphylaxis (POA), tryptase measurement is more common. The appropriate timing of blood collection and the diagnostic threshold for histamine measurement are still controversial. To address these issues, histamine concentrations in patients with anaphylaxis and those with anaphylaxis-uncertain were compared in our previous study, the Japanese Epidemiologic Study for Perioperative Anaphylaxis (JESPA). However, because we could not rule out the possibility that the anaphylactic-uncertain group included anaphylactic patients, histamine concentrations were measured in patients who underwent general anesthesia with no complications as controls in the present study. Histamine levels were measured at anesthesia induction (baseline), 30 min (first point), and 2 h (second point) after the start of surgery in 30 control patients. Histamine concentrations in controls were lower than in patients with POA in JESPA at the first and second points. At the first point, a threshold of 1.5 ng/ml resulted in sensitivity of 77% and specificity of 100%. A threshold of 1.1 ng/ml at the second point resulted in sensitivity of 67% and specificity of 87%. Measurement of histamine concentrations within two hours after symptom onset might help diagnose POA.

The Japanese Epidemiologic Study for Perioperative Anaphylaxis, a prospective nationwide study: allergen exposure, epidemiology, and diagnosis of anaphylaxis during general anaesthesia.

BACKGROUND: Diagnosis of perioperative anaphylaxis is often challenging. This study describes the utility of a newly developed tool for identifying patients with a high possibility of anaphylaxis, and aimed to investigate the frequency of anaphylaxis with each drug during the perioperative period in Japan. METHODS: This study included patients with anaphylaxis of Grade 2 or higher severity during general anaesthesia at 42 facilities across Japan in 2019 and 2020. We developed and adopted a unique objective evaluation tool yielding a composite score for diagnosing anaphylaxis, which includes the results of skin tests and basophil activation tests, and clinical scores for perioperative anaphylaxis. The number of cases using each drug and the total number of anaphylaxis cases were investigated to calculate the frequency of anaphylaxis. RESULTS: General anaesthesia was performed in 218 936 cases, which included 55 patients with suspected perioperative anaphylaxis. The developed composite score diagnosed 43 of them with a high probability of anaphylaxis. The causative agent was identified in 32 cases. Plasma histamine levels showed high diagnostic accuracy for anaphylaxis. The top causative agents were rocuronium (10 cases in 210 852 patients, 0.005%), sugammadex (7 cases in 150 629 patients, 0.005%), and cefazolin (7 cases in 106 005 patients, 0.007%). CONCLUSIONS: We developed a composite tool to diagnose anaphylaxis, and found that the combination of tryptase levels, skin testing, and basophil activation testing results and clinical score improved the certainty of anaphylaxis diagnosis. The incidence of perioperative anaphylaxis in our study was 1 in about 5000 general anaesthesia cases. CLINICAL TRIAL REGISTRATION: UMIN000035350.