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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., (Copyright © 2024 Japanese Society of Allergology. Published by Elsevier B.V. All rights reserved.)

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., (© 2023. The Author(s) under exclusive licence to Japanese Society of Anesthesiologists.)

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., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Diagnosis of perioperative anaphylaxis is difficult because of its non-specific and variable signs and symptoms. Therapeutic agents used to treat anaphylaxis and anaesthesiologist responses also vary depending on the case, which might affect outcomes; however, only a few studies have focused on these factors., Methods: This prospective study of perioperative anaphylaxis, a part of the Japanese Epidemiologic Study for Perioperative Anaphylaxis, investigated the clinical signs, its severity, therapeutic drugs, epinephrine administration, and anaesthesiologist responses in cases of perioperative anaphylaxis to assess trends and variability. Shock index was used to assess severity of cardiovascular collapse., Results: In 43 patients analysed in this study, cardiovascular signs (88.4%) were the most frequent, followed by skin (81.4%) and respiratory signs (60.5%). The presence of signs increased during the clinical course. The median time from the first signs to diagnosis of anaphylaxis was 10 (5.0-17.8) min. The rates of epinephrine use were 30.2% (unused), 48.8% (i.v.), and 20.9% (i.m.). The median time from diagnosis of anaphylaxis to epinephrine administration was 7 (inter-quartile range: 1.5-8.0) min. Antihistamines and corticosteroids were each used in 69.8% of cases. The worst shock index was higher in patients who received i.v. epinephrine (2.77 [0.90] mean [standard deviation]) than in both no epinephrine use cases (1.35 [0.41]) and i.m. epinephrine cases (1.89 [0.77] (P<0.001])., Conclusions: The clinical signs and treatments of perioperative anaphylaxis are variable, and the choice regarding epinephrine administration is based on symptom severity., Clinical Trial Registration: UMIN000035350., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Anaphylactic shock is a potentially lethal complication during anesthesia and requires appropriate management to save the patient's life. We report a 32-year-old man who developed anaphylaxis during induction of general anesthesia with remimazolam for hand surgery. He received general anesthesia with midazolam 4 weeks before. This time facial flushing followed by a decrease of peripheral oxygen saturation (SpO 2 ) and blood pressure occurred 2 min after starting continuous remimazolam infusion at 6 mg/kg/h. Hypotension and SpO 2 were recovered by repeated administration of adrenaline. Despite no increase of serum tryptase levels, intradermal allergy tests 4 weeks postoperatively revealed that remimazolam and midazolam were positive, suggesting remimazolam as a causative agent for anaphylaxis. In the previous surgery, midazolam, which has a similar structure to remimazolam, may have caused sensitization. This is probably the first case report of anaphylaxis caused by remimazolam., (© 2021. Japanese Society of Anesthesiologists.)

Since perioperative anaphylaxis occurs suddenly, and it can be life-threatening, anesthesiologists need to have sufficient knowledge of the epidemiology of perioperative anaphylaxis and appropriate coping strategies to deal with it. Recent studies conducted in Western countries reported the characteristics of perioperative anaphylaxis in each country. However, there are few studies of perioperative anaphylaxis in Japan. To bridge the gap between Japan and other countries, the data of 46 anaphylaxis patients at Gunma University Hospital and 13 neighboring hospitals between 2012 and 2018 were collected and analyzed. The recently developed clinical scoring system was combined with a skin test to include only cases with a definite diagnosis. The most common causative agents were sugammadex, followed by rocuronium, cefazolin, and antibiotics other than cefazolin. Furthermore, the characteristics of anaphylaxis for each causative drug were identified. Time from drug administration to appearance of the first symptom was the longest in the cefazolin group. The incidence of canceled operation was the highest in the rocuronium group. Although it is unclear whether the results of this study can apply to Japan as a whole, the information about the agents responsible for perioperative anaphylaxis and the characteristics of anaphylaxis due to each agent would be helpful to anesthesiologists.

Skin tests are the gold standard for detecting the culprit drug of anaphylaxis, and should ideally be performed after an interval of 4-6 weeks after the reaction to avoid false-negative results. However, when re-operation cannot be delayed and early allergy tests are necessary, special attention is required during subsequent anesthesia, because early skin tests tend to produce false-negative results. This report presents a case of rocuronium-induced anaphylaxis in which early skin tests showed negative results for all the drugs tested. The second anesthesia was safely performed by avoiding all the drugs used for the first anesthesia. Ultimately, skin tests and basophil activation tests (BATs) performed after re-operation demonstrated rocuronium as the drug responsible for anaphylaxis. We recommend performing BATs in addition to skin tests to improve the accuracy of diagnosis of anaphylaxis. In this report, we also discuss interpretation of the results of early skin tests and subsequent selection of drugs for anesthesia. After postponement of surgery due to anaphylaxis, we are often required to perform allergy tests at an early stage if re-operation cannot be delayed. In such cases, skin test results alone should not be used to guide subsequent anesthesia management to avoid recurrent anaphylaxis.

Background: Although cases of anaphylaxis caused by sugammadex have been reported, its incidence remains uncertain. Conversely, no studies have evaluated the incidence of anaphylaxis to neostigmine., Methods: This was a retrospective multicentre observational study of patients who underwent surgery under general anaesthesia between 2012 and 2016 to compare the incidence of anaphylaxis with sugammadex with that of neostigmine at four tertiary hospitals in Japan. To ensure the quality of diagnosis, only cases with a clinical history suggestive of anaphylaxis, along with positive results from in vitro or in vivo testing, were assessed., Results: From a total of 49 532 patients who received general anaesthesia included in this study, 18 cases of anaphylaxis were reported, of which six were attributable to sugammadex and none to neostigmine. There were no fatalities attributable to anaphylaxis. The incidence of anaphylaxis caused by all drugs or by sugammadex was calculated as 0.036% (95% confidence interval [CI]: 0.022-0.057%) and 0.02% (of the number of sugammadex cases) (95% CI: 0.007-0.044%), respectively., Conclusions: The results suggest that neostigmine might be safer than sugammadex when assessing only the incidence of anaphylaxis. We believe that there is room for reconsideration of the choice of reversal agent for neuromuscular blocking agents by all anaesthetists., Clinical Trial Registration: UMIN000022365; UMIN000033561., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)