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.

Treatment-resistant hiccups during general anesthesia possibly caused by remimazolam: a case report.

BACKGROUND: Previous reports have described hiccups during general anesthesia that were possibly induced by drugs, including benzodiazepines. However, there are few reports of hiccups caused by remimazolam. Case presentation A 75-year-old woman underwent corneal transplantation under general anesthesia with remimazolam. She presented with hiccups once the effects of muscle relaxants used during induction wore off, which persisted even after various treatments, such as the administration of antipsychotic drugs. However, when remimazolam administration was terminated after surgery to awaken the patient, the hiccups stopped and did not recur after extubation. Evaluation of predicted blood levels of remimazolam suggests that higher levels of remimazolam might cause hiccups. CONCLUSION: Remimazolam might induce hiccups during general anesthesia. Anesthesiologists should consider administering muscle relaxants or changing the anesthetic in cases of refractory hiccups under general anesthesia.

Anesthesia management of laparoscopic right colectomy in an older patient with postoperative tetralogy of Fallot with residual anomaly.

BACKGROUND: Diversity in hemodynamics of adult congenital heart disease necessitates a case-by-case selection of appropriate surgical and anesthetic options. However, previous case reports regarding the management of laparoscopic surgery in adult patients with congenital heart disease are limited. CASE PRESENTATION: A 72-year-old man who underwent a laparoscopic right colectomy for colon cancer had a residual ventricular septal defect and right ventricular outflow tract obstruction despite post-repair of tetralogy of Fallot. Pulmonary hypertension or right ventricular dysfunction was not observed. The preoperative pulmonary to systemic blood flow ratio (Qp/Qs) was 2.3. After positive pressure ventilation and insufflation, the amount of left-to-right ventricular shunting decreased, and the Qp/Qs approached 1.0, as calculated from pulmonary arterial and systemic arterial blood gas analysis. CONCLUSIONS: Laparoscopic surgery might be tolerable in patients with tetralogy of Fallot who have preserved the right ventricular function, left-to-right ventricular shunting, and no high pulmonary vascular resistance.

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.

Life-threatening chlorhexidine anaphylaxis caused by skin preparation before chlorhexidine-free central venous catheter insertion: a case report and literature review.

Chlorhexidine is a common cause of perioperative anaphylaxis, and global regulatory authorities have issued warnings about anaphylaxis due to chlorhexidine-containing central venous catheters (CVC) and its mucosal absorption. We present a case of life-threatening anaphylaxis after CVC insertion caused by chlorhexidine used for skin preparation. The onset of anaphylaxis was rapid and very severe, resulting in pulseless electrical activity. The patient was successfully resuscitated by emergency veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Our case suggests that even skin preparation before chlorhexidine-free CVC insertion can cause life-threatening anaphylaxis. We reviewed the literature on chlorhexidine anaphylaxis cases and categorized all potential routes of chlorhexidine exposure to assess the risk following skin preparation. Our results showed that skin preparation before CVC insertion was the third most common cause of chlorhexidine anaphylaxis after transurethral exposure and chlorhexidine-containing CVCs. However, skin preparation with chlorhexidine before CVC insertion was sometimes overlooked as a cause of chlorhexidine anaphylaxis, and its risk might be underestimated. Further, no previous reports have described life-threatening anaphylaxis solely due to chlorhexidine skin preparation before CVC insertion. CVC insertion might cause the chlorhexidine used for skin preparation to reach the vascular system and should be recognized as a potential cause of life-threatening chlorhexidine anaphylaxis.

The Japanese Epidemiologic Study for Perioperative Anaphylaxis, a prospective nationwide study: clinical signs, severity, and therapeutic agents.

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.

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.

Long-Term Prognosis Following Early Rehabilitation in the ICU: A Retrospective Cohort Study.

OBJECTIVES: Critically ill patients often have residual functional disabilities. Studies have shown that early rehabilitation improves short-term physical function. However, it remains unknown whether early rehabilitation affects long-term prognosis and healthcare resource utilization. DESIGN: Retrospective cohort study. SETTING: This study used an administrative claims database in Kumamoto Prefecture, Japan, from April 2012 to February 2017. PATIENTS: We identified patients who were admitted to the ICU and received rehabilitation. Eligible patients were divided into those who underwent rehabilitation within 3 days (early rehabilitation group) and after 4 or more days of ICU admission (delayed rehabilitation group). Propensity score matching analyses were conducted to compare the number of outpatient consultations within 1 year and 3 years after discharge from the index hospitalization, total duration of hospitalization after discharge, healthcare costs, and survival. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 6,679 patients were included in the study. Propensity score matching created 2,245 pairs. No difference was observed in the number of outpatient consultations 1 year after discharge, although there were differences between the groups 3 years after discharge. Long-term observation revealed a shorter overall duration of hospitalization (1.9 vs 2.6 mo; p < 0.001) and lower total costs ($28,159 vs $38,272; p < 0.001), as well as lower average costs per month ($1,690 vs $1,959; p = 0.001) in the early compared with the delayed rehabilitation group. No differences in survival were observed (log-rank test; p = 0.18). CONCLUSIONS: Starting rehabilitation within 3 days of ICU admission was associated with shorter durations of future hospitalization and lower healthcare costs. Early rehabilitation for ICU patients might be associated with reduced healthcare resource utilization.

Prevention of Postoperative Cognitive Dysfunction by Minocycline in Elderly Patients after Total Knee Arthroplasty: A Randomized, Double-blind, Placebo-controlled Clinical Trial.

BACKGROUND: There are no effective pharmacologic interventions for preventing postoperative cognitive dysfunction in daily practice. Since the antibiotic minocycline is known to suppress postoperative neuroinflammation, this study hypothesized and investigated whether minocycline might have a preventive effect on postoperative cognitive dysfunction after noncardiac surgery. METHODS: This study included patients aged more than 60 yr undergoing total knee arthroplasty under general anesthesia. They were randomly assigned to minocycline and placebo groups, to orally receive 100 mg of minocycline or placebo twice daily from the day before surgery until the seventh day after surgery. Cognitive function was evaluated before surgery, and 1 week and 3 months after surgery, using a battery of four cognitive function tests, including Visual Verbal Learning Test, Trail Making Test, Stroop Color and Word Test, and Letter-Digit Coding Task. Additionally, 30 healthy volunteers were subjected to the same tests as the patients to examine the learning effect of repeated tests. The occurrence of postoperative cognitive dysfunction was judged from the results of the neurocognitive test battery, with consideration of the learning effect. The secondary endpoints were the effects of minocycline on postoperative delirium and postoperative pain. RESULTS: A total of 100 patients were randomized to the minocycline group, and 102 were randomized to the placebo group. The average age of patients was 75 yr. Evaluation showed no significant difference in the incidence of postoperative cognitive dysfunction between the minocycline and placebo groups at both 1 week (8 of 90 [8.9%] vs. 4 of 95 [4.2%]; odds ratio, 2.22 [95% CI, 0.64 to 7.65]; P = 0.240) and 3 months (15.3 of 90 [17.0%] vs. 15.3 of 95 [16.1%]; odds ratio, 1.07 [95% CI, 0.49 to 2.32]; P = 0.889) postoperatively. Missing data 3 months after surgery were corrected by the multiple imputation method. There were no differences between the two groups in postoperative delirium and postoperative pain. CONCLUSIONS: Minocycline is likely to have no preventive effect on postoperative cognitive dysfunction.

Intraoperative chlorhexidine-induced anaphylaxis suggesting an immunoglobulin-E-dependent mechanism indicated by basophil activation tests: two case reports.

BACKGROUND: Although chlorhexidine allergy has been shown to be mediated by immunoglobulin (Ig) E, few reports investigated the mechanism of chlorhexidine-induced anaphylaxis using basophil activation tests (BATs). CASE PRESENTATION: A 79-year-old man underwent cholecystectomy under general anesthesia. Anaphylaxis was diagnosed based on the clinical symptoms and high serum tryptase and histamine levels. Skin tests showed positive results only for chlorhexidine. Subsequently, BATs demonstrated that the causative agent was likely chlorhexidine. The inhibitory effect of wortmannin, an inhibitor of phosphoinositide 3-kinase, on basophil activation suggested an IgE-dependent mechanism underlying chlorhexidine-induced anaphylaxis. An 89-year-old man underwent inguinal hernioplasty under general anesthesia. Anaphylaxis was diagnosed based on the clinical symptoms and high serum tryptase and histamine levels. Skin tests and BATs with wortmannin were performed, showing similar results to case 1. CONCLUSIONS: BATs suggested an IgE-dependent mechanism for chlorhexidine-induced anaphylaxis and might be useful for investigating the mechanisms underlying drug-induced anaphylaxis.

Risk factors for mechanical ventilation and ECMO in COVID-19 patients admitted to the ICU: A multicenter retrospective observational study.

BACKGROUND: The primary purpose of this study was to investigate risk factors associated with the need for mechanical ventilation (MV) and extracorporeal membrane oxygenation (ECMO) in COVID-19 patients admitted to the intensive care unit (ICU). METHODS: We retrospectively enrolled 66 consecutive COVID-19 patients admitted to the ICUs of three Japanese institutions from February 2020 to January 2021. We performed logistic regression analyses to identify risk factors associated with subsequent MV and ECMO requirements. Further, multivariate analyses were performed following adjustment for Acute Physiology and Chronic Health Evaluation (APACHE) II scores. RESULTS: At ICU admission, the risk factors for subsequent MV identified were: higher age (Odds Ratio (OR) 1.04, 95% Confidence Interval (CI) 1.00-1.08, P = 0.03), higher values of APACHE II score (OR 1.20, 95% CI 1.08-1.33, P < 0.001), Sequential Organ Failure Assessment score (OR 1.53, 95% CI 1.18-1.97, P < 0.001), lactate dehydrogenase (LDH) (OR 1.01, 95% CI 1.00-1.02, p<0.001) and C-reactive protein (OR 1.09, 95% CI 1.00-1.19, P = 0.04), and lower values of lymphocytes (OR 1.00, 95% CI 1.00-1.00, P = 0.02) and antithrombin (OR 0.95, 95% CI 0.91-0.95, P < 0.01). Patients who subsequently required ECMO showed lower values of estimated glomerular filtration rate (OR 0.98, 95% CI 0.96-1.00, P = 0.04) and antithrombin (OR 0.94, 95% CI 0.88-1.00, P = 0.03) at ICU admission. Multivariate analysis showed that higher body mass index (OR 1.19, 95% CI 1.00-1.40, P = 0.04) and higher levels of LDH (OR 1.01, 95% CI 1.01-1.02, P < 0.01) were independent risk factors for the need for MV. Lower level of antithrombin (OR 0.94, 95% CI 0.88-1.00, P = 0.03) was a risk factor for the need for ECMO. CONCLUSION: We showed that low antithrombin level at ICU admission might be a risk factor for subsequent ECMO requirements, in addition to other previously reported factors.

Local anesthetic lidocaine induces growth suppression of HeLa cells by decreasing and changing the cellular localization of the proliferation marker Ki-67.

Although surgery is a basic therapy for cancer, it causes inflammation and immunosuppression, often resulting in recurrence and metastasis. Previous studies have suggested that anesthetic management influences the prognosis of cancer surgery patients. Administration of local anesthetics, such as lidocaine, for pain control reportedly improves their clinical outcomes; however, the precise underlying mechanism has not been fully elucidated. The growth of human embryonic kidney (HEK) 293T and cervical cancer HeLa cells was inhibited by lidocaine treatment and these cell lines showed different sensitivities for lidocaine. Ki-67 is a significant prognostic marker of cancer because it is expressed in the nucleus of actively proliferating cells. In lidocaine-treated HeLa cells, Ki-67 was detected not only in the nucleus but also in the cytoplasm. In addition, lidocaine-induced cytoplasmic Ki-67 partly colocalized with the increased ER chaperone, glucose-regulated protein 78, which is crucial for protein folding and maintenance of cellular homeostasis. Furthermore, lidocaine decreased Ki-67 levels and increased the population of HeLa cells in the G0/G1 phase. These results indicate that lidocaine plays a significant role in growth suppression by regulating the expression and distribution of Ki-67.

Local anesthetic lidocaine-inducible gene, growth differentiation factor-15 suppresses the growth of cancer cell lines.

Administration of local anesthetics, such as lidocaine, in the perioperative period improves outcomes of cancer patients. However, its precise mechanism is still unresolved. The growth of human cancer cell lines, including HeLa cells, are suppressed by lidocaine treatment. We identified that growth differentiation factor-15 (GDF-15) was commonly upregulated in lidocaine-treated cancer cell lines. GDF-15 is a divergent member of the transforming growth factor-ß (TGF-ß) superfamily and it is produced as an unprocessed pro-protein form and then cleaved to generate a mature form. In lidocaine-treated HeLa cells, increased production of GDF-15 in the endoplasmic reticulum (ER) was observed and unprocessed pro-protein form of GDF-15 was secreted extracellularly. Further, lidocaine induced apoptosis and apoptosis-inducible Tribbles homologue 3 (TRIB3) was also commonly upregulated in lidocaine-treated cancer cell lines. In addition, transcription factor C/EBP homologous protein (CHOP), which is a positive regulator of not only GDF-15 but TRIB3 was also induced by lidocaine. Lidocaine-induced growth suppression and apoptosis was suppressed by knockdown of GDF-15 or TRIB3 expression by small interference RNA (siRNA). These observations suggest that lidocaine suppresses the growth of cancer cells through increasing GDF-15 and TRIB3 expression, suggesting its potential application as cancer therapy.

Investigation of the optimal method of oxygen administration with simultaneous use of a surgical mask: a randomized control study.

PURPOSE: From the perspective of infection prevention during the Coronavirus disease 2019 (COVID-19) pandemic, a recommendation was made to use surgical masks after extubation in patients in the operating room. For compliance with this recommendation, anesthesiologists need to administer oxygen to the patient with an oxygen mask over the surgical mask. However, no studies have investigated whether this method allows good maintenance of oxygenation in patients. This study aimed to investigate which method of oxygen administration lends itself best to use with a surgical mask in terms of oxygenation. METHOD: We administered oxygen to the study subjects using all the following three methods in random order: an oxygen mask over or under a surgical mask and a nasal cannula under the surgical mask. Oxygenation was assessed using the oxygen reserve index (ORi) and end-tidal oxygen concentration (EtO2). RESULT: This study included 24 healthy volunteers. ORi values with administration of oxygen were higher in the order of a nasal cannula under the surgical mask, an oxygen mask under the surgical mask, and an oxygen mask over the surgical mask, with median values of 0.50, 0.48, and 0.43, respectively, and statistically significant differences between all groups (P < 0.001). EtO2 values were in the same order as ORi, with median values of 33.0%, 31.0%, and 25%, respectively, and statistically significant differences between all groups (P < 0.001). CONCLUSION: Wearing a surgical mask over the nasal cannula during oxygen administration is beneficial for oxygenation and might help prevent aerosol dispersal.

Practical guidelines for the response to perioperative anaphylaxis.

Perioperative anaphylaxis is a severe adverse event during anesthesia that requires prompt diagnosis and treatment by physicians, including anesthesiologists. Muscle relaxants and antibiotics are the most common drugs that cause perioperative anaphylaxis in Japan, as in many countries. In addition, sugammadex appears to be a primary causative agent. Obtaining previous anesthesia records is necessary in a patient with a history of allergic reactions during anesthesia, whenever possible, to avoid recurrence of anaphylaxis. Although medical staff are likely to notice abnormal vital signs because of complete monitoring during anesthesia, surgical drapes make it difficult to notice the appearance of skin symptoms. Even if there are no skin symptoms, anaphylaxis should be suspected, especially when hypotension resistant to inotropes and vasopressors persists. For improving the diagnostic accuracy of anaphylaxis, it is helpful to collect blood samples to measure histamine/tryptase concentrations immediately after the events and at baseline. The first-line treatment for anaphylaxis is adrenaline. In the perioperative setting, adrenaline should be administered through the intravenous route, which has a faster effect onset and is secured in most cases. Adrenaline can cause serious complications including severe arrhythmias if the appropriate dose is not selected according to the severity of symptoms. The anesthesiologist should identify the causative agent after adverse events. The gold standard for identifying the causative agent is the skin test, but in vitro tests including specific IgE antibody measurements and basophil activation tests are also beneficial. The Working Group of the Japanese Society of Anesthesiologists has developed this practical guide to help appropriate prevention, early diagnosis and treatment, and postoperative diagnosis of anaphylaxis during anesthesia.Grade of recommendations and levels of evidence Anaphylaxis is a relatively rare condition with few controlled trials, and thus a so-called evidence-based scrutiny is difficult. Therefore, rather than showing evidence levels and indicating the level of recommendation, this practical guideline only describes the results of research available to date. The JSA will continue to investigate anaphylaxis during anesthesia, and the results may lead to an amendment of this practical guideline.

Impact of the First Wave of COVID-19 on the Number of General Anesthesia Cases in 34 Tertiary Hospitals in Japan: A Multicenter Retrospective Study.

Since the first case of coronavirus disease 2019 (COVID-19) was reported in Japan in January 2020, the COVID-19 pandemic has brought about a significant change in people's lives. Although the COVID-19 pandemic is expected to have had an impact on the work of anesthesiologists, the specific impact has been largely unreported. We hypothesized that the number of general anesthesia (GA) cases has decreased due to the COVID-19 pandemic. To test this hypothesis, we conducted a retrospective survey at 34 facilities in Japan as a part of the Japanese Epidemiologic Study for Perioperative Anaphylaxis. The results showed that the number of GA cases had significantly decreased, particularly in May 2020, under the government's declaration of a state of emergency. The decline in GA caseload had not fully recovered by July 2020. Furthermore, there were regional differences in the decline in the number of GA cases. The impact of the COVID-19 pandemic on the work of anesthesiologists was greater in prefectures where there were more COVID-19 patients and where the state of emergency was declared earlier. Our study suggested a region-dependent decrease in the number of GA cases due to the COVID-19 pandemic.

Intraoperative anaphylaxis due to aprotinin after local application of fibrin sealant diagnosed by skin tests and basophil activation tests: a case report.

BACKGROUND: There are few cases of anaphylaxis after local application of fibrin sealant diagnosed by skin tests. CASE PRESENTATION: A 49-year-old woman underwent partial lung resection under general anesthesia. Anesthesia was induced uneventfully. Shortly after applying absorbable suture reinforcement felt that contained fibrin sealant, her systolic blood pressure fell to approximately 70 mmHg, along with facial flushing. Anaphylaxis was diagnosed based on the clinical symptoms and high serum tryptase levels. Three months after the event, skin tests were performed with all agents and were positive only for fibrin sealant vial no. 2, whose main component is aprotinin. Subsequently, basophil activation tests using fibrin sealant vial no. 2 and pure aprotinin demonstrated that the causative agent was likely aprotinin. CONCLUSIONS: We diagnosed aprotinin-induced anaphylaxis using skin tests and basophil activation tests. The occurrence of anaphylaxis should be considered when changes in vital signs are observed after the use of fibrin sealant.