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.

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.

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.

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.

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.

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.

Drug-induced anaphylaxis during general anesthesia in 14 tertiary hospitals in Japan: a retrospective, multicenter, observational study.

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.

Remimazolam anaphylaxis during anesthesia induction.

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 (SpO2) and blood pressure occurred 2 min after starting continuous remimazolam infusion at 6 mg/kg/h. Hypotension and SpO2 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.

Comparison of incidence of anaphylaxis between sugammadex and neostigmine: a retrospective multicentre observational study.

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.

History of the development of antagonists for neuromuscular blocking agents.

Muscle relaxation induced by neuromuscular blocking agents (NMBAs) is necessary for tracheal intubation and immobilization during surgery. Although acetylcholinesterase inhibitors have been successfully used as antagonists for NMBAs, they have their limitations; their effects are transient and ineffective against profound neuromuscular blockade. In the past, alternative antagonists were developed, such as germine and 4-aminopyridine, which are effective for the treatment of diseases causing muscle weakness and could potentially be used as antagonists for NMBAs. Unfortunately, these drugs did not come into practical use due to unwanted side-effects. Sugammadex is an almost ideal antagonist because it rapidly forms a rigid complex with rocuronium and produces less adverse effects. The development of novel NMBAs and antagonists, especially sugammadex, has revolutionized anesthesia practice. Recently, novel short-acting NMBAs, such as gantacurium and CW002 have been developed. Their effects can be reversed by the amino-acid L-cysteine. More recently, calabadions have been developed, which can form complexes with both steroidal and bisbenzyl-isoquinolinium NMBAs, in a similar fashion as sugammadex. Understanding the history of the NMBA antagonist's development is interesting and useful for modern anesthesiologists since it enhances their knowledge about the mechanisms involved in neuromuscular transmission and might lead to the development of ideal NMBA antagonists.

Interpreting the results of early skin tests after perioperative anaphylaxis requires special attention: a case report and review of literature.

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.

Hemodynamically adjusted infrahepatic inferior venous cava clamping can reduce postoperative deterioration in renal function: a retrospective observational study.

PURPOSE: Infrahepatic inferior vena cava (IIVC) clamping is beneficial for reducing the amount of bleeding during hepatic surgery, although the associated systemic circulatory deterioration is noticeable. The relationship between changes in the degree of IIVC clamping and postoperative renal function was retrospectively evaluated. METHODS: A total of 59 patients who underwent elective hepatic surgery with surgical IIVC clamping in the two years were analyzed. In 2016, constant 80% clamping of the IIVC was performed (29 cases), and in 2017, hemodynamically adjusted IIVC clamping was performed (30 cases). Intraoperative parameters, including total blood loss and number of blood transfusions, were examined. The use of each vasoactive agents was analyzed. Renal function in the acute postoperative phase was evaluated using serum creatinine (Cr) and estimated glomerular filtration rate (eGFR) values. RESULTS: Comparison of the two groups showed that bolus doses of both ephedrine and phenylephrine were significantly higher in the 2016 group (P = 0.0221, 0.0017). Continuous doses of dopamine were significantly higher in the 2016 group, while those of noradrenaline were not. Postoperative serum Cr levels relative to baseline (%) were significantly higher in the 2016 group immediately after surgery and on postoperative day (POD) 1 (P = 0.0143, 0.0012). Postoperative eGFR relative to baseline (%) was significantly higher in the 2016 group immediately postoperatively and on PODs 1 and 2 (P = 0.0042, 0.0003, 0.0382). CONCLUSION: Hemodynamically adjustable IIVC clamping might be superior to uniformly fixed clamping in preserving renal function without compromising the desired effect on hemostasis.

In vitro diagnostic tests for perioperative hypersensitivity, a narrative review: potential, limitations, and perspectives.

Correct diagnostic management of perioperative hypersensitivity aims to identify the underlying mechanism(s), responsible culprit(s), and safe alternative drugs or techniques. Although drug provocation tests are considered the gold standard, diagnosis of perioperative hypersensitivity mainly relies on skin testing. Use of in vitro tests, such as quantification of specific immunoglobulin E antibodies, serum tryptase, and plasma histamine, as well as basophil activation tests is becoming widespread. These latter tests have the advantage of having no risk of recurrence of immediate hypersensitivity reactions. In this narrative review, we summarise the principles of these in vitro tests, and the possibilities and limitations when these tests are used for testing sensitivity to substances with a high risk of causing perioperative hypersensitivity. Hence, we focus on neuromuscular blocking agents, antibiotics, natural rubber latex, and opiates/opioids. The combination of multiple tests would allow diagnosis of perioperative hypersensitivity with the right balance of safety and accuracy.

The use of drug provocation testing in the investigation of suspected immediate perioperative allergic reactions: current status.

Suspected perioperative allergic reactions are often severe. To avoid potentially life-threatening re-exposure to the culprit drug, establishing a firm diagnosis and identifying the culprit is crucial. Drug provocation tests are considered the gold standard in drug allergy investigation but have not been recommended in the investigation of perioperative allergy, mainly because of the pharmacological effects of drugs such as induction agents and neuromuscular blocking agents. Some specialised centres have reported benefits of provocation testing in perioperative allergy investigation, but the literature on the subject is limited. Here we provide a status update on the use of drug provocation testing in perioperative allergy, including its use in specific drug groups. This review is based on a literature search and experiences of the authors comprising anaesthesiologists and allergists with experience in perioperative allergy investigation. In addition, 19 participating centres in the International Suspected Perioperative Allergic Reaction Group were surveyed on the use of provocation testing in perioperative allergy investigation. A response was received from 13 centres in eight European countries, New Zealand, and the USA. Also, 21 centres from the Australian and New Zealand Anaesthetic Allergy Group were surveyed. Two centres performed provocation routinely and seven centres performed no provocations at all. Nearly half of the centres reported performing provocations with induction agents and neuromuscular blocking agents. Drug provocation testing is being used in perioperative allergy investigation in specialised centres, but collaborations between relevant specialties and multicentre studies are necessary to determine indications and establish common testing protocols.

Management of suspected immediate perioperative allergic reactions: an international overview and consensus recommendations.

Suspected perioperative allergic reactions are rare but can be life-threatening. The diagnosis is difficult to make in the perioperative setting, but prompt recognition and correct treatment is necessary to ensure a good outcome. A group of 26 international experts in perioperative allergy (anaesthesiologists, allergists, and immunologists) contributed to a modified Delphi consensus process, which covered areas such as differential diagnosis, management during and after anaphylaxis, allergy investigations, and plans for a subsequent anaesthetic. They were asked to rank the appropriateness of statements related to the immediate management of suspected perioperative allergic reactions. Statements were selected to represent areas where there is a lack of consensus in existing guidelines, such as dosing of epinephrine and fluids, the management of impending cardiac arrest, and reactions refractory to standard treatment. The results of the modified Delphi consensus process have been included in the recommendations on the management of suspected perioperative allergic reactions. This paper provides anaesthetists with an overview of relevant knowledge on the immediate and postoperative management of suspected perioperative allergic reactions based on current literature and expert opinion. In addition, it provides practical advice and recommendations in areas where consensus has been lacking in existing guidelines.

Comparative epidemiology of suspected perioperative hypersensitivity reactions.

Suspected perioperative hypersensitivity reactions are rare but contribute significantly to the morbidity and mortality of surgical procedures. Recent publications have highlighted the differences between countries concerning the respective risk of different drugs, and changes in patterns of causal agents and the emergence of new allergens. This review summarises recent information on the epidemiology of perioperative hypersensitivity reactions, with specific consideration of differences between geographic areas for the most frequently involved offending agents.