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]: 0.022e0.057%) and 0.02% (of the number of sugammadex cases) (95% CI: 0.007e0.044%), 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.

BackgroundSugammadex has a unique mechanism of action and is widely used because of its safety and efficacy. A few recent reports have described allergic reactions to clinical doses of sugammadex. We hereby describe another series of cases of possible anaphylaxis to sugammadex.Case presentationWe present three suspected cases of sugammadex-induced anaphylactic shock, including a 13-year-old boy who underwent laparoscopic appendectomy, a 75-year-old woman who underwent left knee arthroplasty, and a 34-year-old man who underwent left pansinectomy for sinobronchitis. All three patients received general anesthesia with rocuronium and their tracheas were intubated. Shortly after injection of sugammadex for reversal of rocuronium, all of them experienced a decrease in blood pressure along with mucocutaneous erythema. In the most severe case, reintubation after extubation was required due to difficulty in manual ventilation. All patients recovered with anti-allergic therapy. On later investigation, all three patients had a positive skin reaction to sugammadex.ConclusionOur results suggest that physicians using sugammadex should be aware of the possibility of sugammadex-induced anaphylaxis.

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.

The BAT seems to have comparable accuracy to skin tests for the diagnosis of sugammadex-induced anaphylaxis. For this purpose, both CD203c and CD63 can be used to detect activated basophils.

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.