Journal of Anesthesia

https://doi.org/10.1007/s00540-020-02886-5

SHORT COMMUNICATION

Drug‑induced anaphylaxis during general anesthesia in 14 tertiary

hospitals in Japan: a retrospective, multicenter, observational study
Tatsuo Horiuchi1 · Tomonori Takazawa2   · Masaki Orihara1 · Shinya Sakamoto1 · Kazuhiro Nagumo1 ·
Shigeru Saito1,2

Received: 11 June 2020 / Accepted: 7 December 2020

© The Author(s) 2021

Abstract
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 opera-
tion 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.

Keywords  Anaphylaxis · Sugammadex · Rocuronium · Cefazolin · Antibiotics

Introduction treatment [1]. Therefore, anesthesiologists need to have suf-

ficient knowledge of the epidemiology of perioperative ana-
Intraoperative complications can be minimized by proper phylaxis and appropriate coping strategies to deal with it.
monitoring and medication based on relevant preoperative Given these circumstances, large-scale epidemiological
assessment. However, due to the difficulty of predicting the studies have recently been conducted in Western countries,
occurrence of anaphylaxis, the risk of developing periopera- and they suggested large differences in the characteristics of
tive anaphylaxis cannot be reduced even with these efforts. perioperative anaphylaxis among countries [2–7]. Unlike the
Although the severity of reactions ranges from mild to situation in other countries, however, little research has been
severe, in extreme cases, anaphylaxis may be fatal despite done in Japan. The last epidemiological survey of periop-
prompt recognition, prolonged adequate resuscitation, and erative anaphylaxis in Japan was conducted 28 years ago
[8]. To bridge the gap between Japan and other countries,
we decided to collect and analyze the data of anaphylaxis
Supplementary Information  The online version contains occurring at Gunma University Hospital and 13 neighboring
supplementary material available at https​://doi.org/10.1007/s0054​ hospitals in the past 7 years. Since perioperative anaphy-
0-020-02886​-5.
laxis is often difficult to diagnose, the recently developed
* Tomonori Takazawa clinical scoring system [9] was combined with a skin test to
takazawt@gunma‑u.ac.jp include only cases with a definite diagnosis. We expect that
this research would enable us to recognize the characteristics
1
Department of Anesthesiology, Gunma University Graduate of perioperative anaphylaxis occurring in Japan.
School of Medicine, Maebashi, Gunma 371‑8511, Japan
2
Intensive Care Unit, Gunma University Hospital, 3‑39‑15
Showa‑machi, Maebashi, Gunma 371‑8511, Japan

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Vol.:(0123456789)
 Journal of Anesthesia

Materials and methods To investigate the characteristics of anaphylaxis for

each causative agent, patients were divided into the follow-
This retrospective, observational study conformed to the ing five groups: sugammadex, rocuronium, cefazolin, anti-
standards of the Declaration of Helsinki and was approved biotics other than cefazolin, and miscellaneous. Although
by the ethics committee of Gunma University [identifi- there were no significant differences in sex, age, clinical
cation (ID): 150034]. The study was registered with the symptoms, and severity grade, the characteristics of ana-
University Hospital Medical Information Network Clini- phylaxis for each causative drug emerged (Table 2). First,
cal Trials Registry (ID: 000022365). Some of the cases the timing of symptom appearance had distinct character-
included in this study have already been presented in our istics. That is, rocuronium-induced anaphylaxis occurred
previous reports, which had different perspectives from the during induction of anesthesia, antibiotic-induced ana-
present study [10–14]. phylaxis occurred during maintenance of anesthesia, and
The patients diagnosed with anaphylaxis between Jan sugammadex-induced anaphylaxis occurred at the end of
2012 and Dec 2018 in Gunma University Hospital and 13 anesthesia. There was only one exception. Second, the
Japanese tertiary hospitals were included in this study. time from drug administration to the appearance of the
Anaphylaxis was diagnosed only when the following two first symptom was the longest in the cefazolin group, sig-
criteria were fulfilled: (1) evaluation using the clinical nificantly longer than in the sugammadex group (p < 0.05,
monitoring scoring system suggested the possibility of one-way ANOVA with the post hoc Dunn’s test). Third,
an immediate hypersensitivity reaction (net total score the incidence of cancelled operation was the highest in the
on the clinical grading scale ≥ 8) [9]; and (2) skin tests rocuronium group, significantly higher than in the sugam-
showed a positive reaction to any of the agents that the madex group (p < 0.05, Fisher’s exact test with the post
patient was exposed to during anesthesia. Patient infor- hoc Bonferroni test).
mation regarding the clinical background, the timing of
symptom appearance, time from administration of the
drug to appearance of the first symptom, types of clinical Discussion
symptoms, net total score on the clinical grading scale,
severity grade, and outcome was collected. The clinical This study summarized the causative agents in 46 cases of
symptoms were classified into four categories, including perioperative anaphylaxis that occurred in the past 7 years
cardiovascular, respiratory, cutaneous, and gastrointesti- and the characteristics of each causative agent.
nal. The severity of clinical symptoms was assessed using Sugammadex was the most common causative agent of
the ring and Messmer scale [15]. perioperative anaphylaxis, which differed from past stud-
Continuous variables are reported by the median and ies conducted in foreign countries and may be a feature of
interquartile range values. The differences in continu- anaphylaxis occurring in Japanese hospitals. Although vari-
ous variables among agents were analyzed with one-way ous factors are considered, high usage of sugammadex in
ANOVA or Kruskal–Wallis one-way ANOVA on ranks. Japan might be one of the reasons [13, 16]. This situation
Categorical variables were analyzed with Fisher’s exact appears to be different from other countries. For example,
test. Sigma plot 14.0 (Systat Software Inc, San Jose, CA) the amount of sugammadex used per case of general anes-
or R ver. 3.3.3 was used for the analyses. Differences were thesia in Japan is expected to be 22.8 times greater than that
considered significant at a p value < 0.05. in the UK [13].
Regarding the neuromuscular blocking agents (NMBAs),
rocuronium is also the top causative drug in most countries
other than Japan. For example, in Australia, rocuronium was
Results responsible for 56% of cases of NMBA-induced anaphylaxis,
succinylcholine 21%, and vecuronium 11% [17]. In the pre-
A total of 49 patients with suspected anaphylaxis due to sent study, however, no anaphylaxis was observed due to
their clinical symptoms were initially investigated. Three NMBAs other than rocuronium, which might again reflect
of these patients had negative skin test reactions for all the high use of rocuronium in Japan [13].
drugs to which they had been exposed during anesthe- Even greater differences between Japan and other
sia; therefore, 46 patients were ultimately included in this countries may be seen for antibiotic-induced anaphylaxis.
study (Table 1). The common causative agents were as Although there are few data on perioperative antibiotics used
follows: sugammadex (n = 13, 28.3%), rocuronium (n = 10, in each country, NAP6 data from a study conducted in the
21.7%), cefazolin (n = 8, 17.4%), and antibiotics other than UK are available: gentamicin was used most often (34.5%),
cefazolin (n = 7, 15.2%) (Table 2, Supplemental Fig. 1). followed by amoxicillin/clavulanic acid (29.8%) and cefuro-
xime (23.7%) [2]. Although there are no national data on

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 Table 1  Clinical backgrounds, causative agents, timing and onset of the appearance of symptoms, anaphylactic symptoms, severity grades, clinical scores, and outcomes in patients with periop-
erative anaphylaxis
Patient no. Age (years) Sex Causative agent Timing Onset (min) Symptoms Severity Clinical score Cancelled Delayed
grade operation extuba-
tion
Journal of Anesthesia

1 75 F Sugammadex End 3 Ca, Cu 3 25 −  + 

2 34 M Sugammadex End 1 Ca, Cu 2 19 − −
3 13 M Sugammadex End 5 Ca, Cu, Re 3 30 −  + 
4 65 M Sugammadex End < 1 Ca, Cu, Re 3 27 −  + 
5 39 M Sugammadex End 8 Ca, Cu 2 17 − −
6 62 M Sugammadex End 3 Ca, Ga 3 13 − −
7 64 F Sugammadex End 3 Ca, Cu 2 21 −  + 
8 33 F Sugammadex End 5 Ca, Cu 2 19 − −
9 46 F Sugammadex End 3 Ca, Cu, Re 3 30 −  + 
10 66 M Sugammadex End 3 Ca, Cu, Re 3 28 − −
11 19 F Sugammadex End 3 Ca, Cu, Re 3 30 −  + 
12 42 F Sugammadex End 3 Ca, Cu, Ga 3 15 − −
13 55 M Sugammadex End 3 Ca, Cu 3 17 − −
14 41 F Rocuronium Induction < 1 Ca, Re 4 35  +  −
15 52 F Rocuronium Induction 5 Ca, Cu, Re 3 28 − −
16 56 F Rocuronium Induction 5 Ca, Re 2 22 −  + 
17 74 F Rocuronium Maintenance 20 Ca, Cu 3 11 − −
18 16 M Rocuronium Induction 5 Ca, Cu 3 23  +  −
19 72 M Rocuronium Induction 3 Ca 3 17  +  −
20 38 F Rocuronium Induction 3 Ca, Cu, Re 2 22  +   + 
21 83 F Rocuronium Induction 10 Ca, Cu 2 17  +  −
22 78 F Rocuronium Induction 10 Ca, Cu, Re 2 19 − −
23 36 M Rocuronium Induction 3 Ca, Cu, Re 2 28  +  −
24 71 F Cefazolin Maintenance 10 Ca, Cu 3 21  +   + 
25 26 F Cefazolin Maintenance 2 Ca, Re 3 26  +   + 
26 67 F Cefazolin Maintenance 3 Ca, Cu 2 21 − −
27 7 F Cefazolin Maintenance 10 Ca, Re 3 22  +  −
28 33 F Cefazolin Maintenance 20 Ca, Cu 3 12 − −
29 77 M Cefazolin Maintenance 10 Ca, Cu, Re 3 20 − −
30 51 M Cefazolin Maintenance 10 Ca, Cu 3 19  +  −
31 14 M Cefazolin Maintenance 10 Ca, Cu 2 24 − −
32 56 M Cefoperazone/Sulbactam Maintenance 5 Ca, Re 4 32 −  + 
33 49 F Cefmetazole Maintenance 5 Ca, Cu 3 23 − −
34 36 F Cefmetazole Maintenance 5 Ca, Cu 2 17 − −

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35 77 M Vancomycin Maintenance 5 Ca, Cu 4 28 − −


Table 1  (continued)
Patient no. Age (years) Sex Causative agent Timing Onset (min) Symptoms Severity Clinical score Cancelled Delayed
grade operation extuba-

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tion

36 86 M Ceftriaxone Maintenance 5 Ca, Cu 3 23  +  −

37 44 F Cefotiam Maintenance 10 Ca, Cu 3 19  +  −
38 25 M Fosfomycin Maintenance 5 Ca, Cu, Re 3 18  +  −
39 54 M Lidocaine Induction < 1 Ca, Cu 3 12 − −
40 42 F Mepivacaine Induction 10 Ca, Cu 3 13 − −
41 21 M Flurbiprofen End 10 Ca, Cu 2 20 − −
42 61 F Propofol Induction < 1 Cu, Re 2 17 − −
43 66 M Fibrin sealant Maintenance 5 Ca, Cu 3 13 − −
44 49 F Fibrin sealant Maintenance 10 Ca, Cu 2 9 − −
45 80 F Atropine Induction 3 Ca, Cu 2 13 − −
46 50 M Iopamidol Maintenance 10 Ca 3 9 − −

The timing of symptom appearance was classified into three categories, including induction, maintenance, and end of anesthesia. The induction of anesthesia refers to within 10  min after
the start of anesthesia. The end of anesthesia means from the end of surgery to the end of anesthesia. Maintenance of anesthesia is the period between induction of anesthesia and the end of
anesthesia. The onset indicates time from drug administration to the appearance of the first symptom. The severity of clinical symptoms was assessed by the Ring and Messmer scale [15]. All
patients had a clinical score of 8 or above, suggesting possible anaphylaxis [9]. Delayed extubation was defined as when the patient was extubated after leaving the operating room, or when it
took more than two hours from the end of surgery to extubation even in the operating room
M male, F female, Ca cardiovascular signs, Cu cutaneous signs, Re respiratory signs, Ga gastrointestinal signs
Journal of Anesthesia
Journal of Anesthesia

Table 2  Characteristics of perioperative anaphylaxis classified by causative agent

Sugammadex Rocuronium Cefazolin Antibiotics Miscellaneous All

Number of patients (%) 13 (28.3) 10 (21.7) 8 (17.4) 7 (15.2) 8 (17.4) 46 (100.0)

Background
Female (%) 6 (46.2) 7 (70.0) 5 (62.5) 3 (42.9) 4 (50.0) 25 (54.3)
Male (%) 7 (53.8) 3 (30.0) 3 (37.5) 4 (57.1) 4 (50.0) 21 (45.7)
Age (years) 47.2 (19.2) 54.6 (22.0) 43.3 (27.0) 53.3 (21.8) 52.9 (17.5) 50.0 (20.9)
Timing
Induction (%) 0 (0.0) 9 (90.0)a 0 (0.0) 0 (0.0) 4 (50.0) 13 (28.3)
Maintenance (%) 0 (0.0) 1 (10.0) 8 (100.0)b 7 (100.0)c 3 (37.5) 19 (41.3)
End (%) 13 (100.0)d 0 (0.0) 0 (0.0) 0 (0.0) 1 (12.5) 14 (30.4)
Onset (min) 3.0 (1.0) 5.0 (7.0) 10.0 (5.3)e 5.0 (0.0) 7.5 (8.5) 5.0 (7.0)
Symptom
Cardiovascular (%) 13 (100.0) 10 (100.0) 8 (100.0) 7 (100.0) 7 (87.5) 45 (97.8)
Respiratory (%) 5 (38.5) 6 (60.0) 3 (37.5) 2 (28.6) 1 (12.5) 17 (37.0)
Cutaneous (%) 12 (92.3) 7 (70.0) 6 (75.0) 6 (85.7) 7 (87.5) 38 (82.6)
Gastrointestinal (%) 2 (15.4) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 2 (4.3)
Clinical score 22.4 (6.2) 22.2 (6.8) 20.6 (4.1) 22.9 (5.5) 13.3 (3.7)f 20.5 (6.4)
Severity grade 3.0 (1.0) 2.5 (1.0) 3.0 (0.8) 3.0 (1.0) 2.5 (1.0) 3.0 (1.0)
Outcome
Cancelled operation (%) 0 (0.0) 6 (60.0)g 4 (50.0) 3 (42.9) 0 (0.0) 13 (28.3)
Delayed extubation (%) 6 (46.2) 2 (20.0) 2 (25.0) 1 (14.3) 0 (0.0) 11 (23.9)

“Antibiotics” refers to antibiotics other than cefazolin. Categorical variables are shown as the actual numbers, and percentages are shown in
parentheses. Since age and clinical score were normally distributed, they are shown as means, and standard deviations are shown in square
brackets. For onset and severity grade, the median values and interquartile ranges are shown. The timing of symptom appearance was classified
into three categories, including induction, maintenance, and end of anesthesia. The induction of anesthesia refers to within 10 min after the start
of anesthesia. The end of anesthesia means from the end of surgery to the end of anesthesia. Maintenance of anesthesia is the period between
induction of anesthesia and the end of anesthesia. The onset indicates the time from drug administration to the appearance of the first sign. The
accuracy of anaphylaxis diagnosis was assessed using the clinical grading scale [9]. The severity of clinical signs was assessed by the Ring and
Messmer scale [15]. Delayed extubation was defined as when the patient was extubated after leaving the operating room, or when it took more
than two hours from the end of surgery to extubation even in the operating room. The symbols indicate significant differences between groups,
and p values were 0.005 or less unless otherwise specified
a
 Rocuronium vs. sugammadex, cefazolin, and antibiotics; bCefazolin vs. rocuronium and sugammadex
c
 Antibiotics vs. rocuronium and sugammadex
d
 Sugammadex vs. all other groups
e
 Cefazolin vs. sugammadex (p < 0.05)
f
 Miscellaneous vs. sugammadex, rocuronium, cefazolin, and antibiotics (p < 0.05)
g
 Rocuronium vs. sugammadex (p < 0.05)

perioperative antibiotic use in Japan, a survey of periopera- by drug (Table 1), this does not necessarily mean that the
tive drugs we recently conducted at four tertiary hospitals causative drug can be determined by the timing alone. For
showed that cefazolin was used in 69% of general anesthesia example, drugs other than rocuronium, including lido-
cases, followed by cefmetazole in 12% (unpublished data). caine and propofol, were also included in the “Induction
Taken together, the reason for the differences in the caus- of anesthesia” category (Table 1). An informed guess,
ative agents of perioperative anaphylaxis in the current study which is based on the relationship between the timing
compared to previous studies might be partially explained of substance exposure and that of symptom appearance,
by the differences in the drugs used. The fact that sugamma- is not a reliable way of determining the cause of a sup-
dex, rocuronium, and cefazolin account for 67% of causative posed allergic reaction [18]. We would emphasize that the
agents (31 of 46 cases) in perioperative anaphylaxis in the cause of anaphylaxis should be identified by allergy tests
present study might be a prominent feature of perioperative such as skin tests. Otherwise, many patients would be at
anaphylaxis in Japan. unnecessary risk.
Although the results of the present study suggest that The median time of onset was the latest in the cefazolin
the timing of anaphylaxis development is clearly different group (Table 2). In some cases with a delayed onset, the

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 Journal of Anesthesia

patient’s body might have already been covered with a Open Access  This article is licensed under a Creative Commons Attri-
surgical drape when the signs of anaphylaxis appeared. bution 4.0 International License, which permits use, sharing, adapta-
tion, distribution and reproduction in any medium or format, as long
In rocuronium-induced anaphylaxis cases, surgery was as you give appropriate credit to the original author(s) and the source,
cancelled in 60%, the highest rate among the groups. In provide a link to the Creative Commons licence, and indicate if changes
general, skin testing is recommended to both find a causa- were made. The images or other third party material in this article are
tive agent and identify alternative NMBAs, especially included in the article’s Creative Commons licence, unless indicated
otherwise in a credit line to the material. If material is not included in
in cases where re-operation is required [16]. Since in the article’s Creative Commons licence and your intended use is not
patients with anaphylaxis due to rocuronium, skin tests permitted by statutory regulation or exceeds the permitted use, you will
were reported to be positive in 44% for succinylcholine, need to obtain permission directly from the copyright holder. To view a
40% for vecuronium, and 5% for cisatracurium, cisatra- copy of this licence, visit http://creat​iveco​mmons​.org/licen​ses/by/4.0/.
curium is recommended for use as an alternative NMBA
[17]. In countries such as Japan where cisatracurium is
not available, anesthesia without NMBAs should be con- References
sidered [16, 19].
1. Mertes PM, Ebo DG, Garcez T, Rose M, Sabato V, Takazawa
This study has several limitations. First, since the loca- T, Cooke PJ, Clarke RC, Dewachter P, Garvey LH, Guttormsen
tion of the participating hospitals was limited to the Kanto AB, Hepner DL, Hopkins PM, Khan DA, Kolawole H, Kopac P,
region, it is unclear whether the results of this study can Kroigaard M, Laguna JJ, Marshall SD, Platt PR, Sadleir PHM,
be applied to Japan as a whole. Second, since the drugs Savic LC, Savic S, Volcheck GW, Voltolini S. Comparative epi-
demiology of suspected perioperative hypersensitivity reactions.
used at each hospital during the study period were not Br J Anaesth. 2019;123(1):e16–28.
investigated, the incidence of anaphylaxis for each drug is 2. Harper NJN, Cook TM, Garcez T, Farmer L, Floss K, Marinho
unknown. Future studies, including the ongoing national S, Torevell H, Warner A, Ferguson K, Hitchman J, Egner W,
epidemiologic study, the Japanese Epidemiological Study Kemp H, Thomas M, Lucas DN, Nasser S, Karanam S, Kong
KL, Farooque S, Bellamy M, McGuire N. Anaesthesia, surgery,
for Perioperative Anaphylaxis (JESPA), will address these and life-threatening allergic reactions: epidemiology and clinical
issues. features of perioperative anaphylaxis in the 6th National Audit
In conclusion, the information obtained from the pre- Project (NAP6). Br J Anaesth. 2018;121(1):159–71.
sent study regarding the agents responsible for periopera- 3. Tacquard C, Collange O, Gomis P, Malinovsky JM, Petitpain N,
Demoly P, Nicoll S, Mertes PM. Anaesthetic hypersensitivity
tive anaphylaxis and the characteristics of anaphylaxis due reactions in France between 2011 and 2012: the 10th GERAP epi-
to each agent would be useful to anesthesiologists. demiologic survey. Acta Anaesthesiol Scand. 2017;61(3):290–9.
4. Harboe T, Guttormsen AB, Irgens A, Dybendal T, Florvaag E.
Acknowledgments  The authors would like to thank Dr. Yukinari Anaphylaxis during anesthesia in Norway: a 6-year single-center
Tomita at Isesaki Municipal Hospital, Dr. Akihiro Tomioka at JCHO follow-up study. Anesthesiology. 2005;102(5):897–903.
Gunma Chuo Hospital, Dr. Nagahide Yoshida at Gunma Saiseikai Mae- 5. Gurrieri C, Weingarten TN, Martin DP, Babovic N, Narr
bashi Hospital, Dr. Kenichiro Takahashi at Japanese Red Cross Ashi- BJ, Sprung J, Volcheck GW. Allergic reactions during anes-
kaga Hospital, Dr. Toshifumi Takahashi at Gunma Prefectural Cancer thesia at a large United States referral center. Anesth Analg.
Center, Dr. Mutsumi Uchiyama at Saitama Cancer Center, Dr. Iwao 2011;113(5):1202–12.
Watanabe at Ogikubo Hospital, Dr. Miyuki Takahashi at Jichi Medical 6. Mertes PM, Volcheck GW, Garvey LH, Takazawa T, Platt PR,
University, Dr. Masayuki Ueno at Saiseikai Utsunomiya Hospital, Dr. Guttormsen AB, Tacquard C. Epidemiology of perioperative ana-
Makoto Sudo at Tatebayashi Public Hospital, Dr. Kazuaki Hagiwara at phylaxis. Presse Med. 2016;45(9):758–67.
Saku Central Hospital Advanced Care Center, and Dr. Toshie Shiraishi 7. Lobera T, Audicana MT, Pozo MD, Blasco A, Fernandez E,
at Yotsuya Medical Cube for their leadership as research representa- Canada P, Gastaminza G, Martinez-Albelda I, Gonzalez-Mahave
tives in each hospital and for their kind advice regarding the interpreta- I, Munoz D. Study of hypersensitivity reactions and anaphylaxis
tion of cases. during anesthesia in Spain. J Investig Allergol Clin Immunol.
2008;18(5):350–6.
Author contributions  Study concept/design: all authors. Data collec- 8. Mitsuhata H, Hasegawa J, Matsumoto S, Ogawa R. The epide-
tion, analysis, and interpretation: TH and TT. Writing of the paper and miology and clinical features of anaphylactic and anaphylactoid
responsibility for its contents: all authors. reactions in the perioperative period in Japan: a survey with a
questionnaire of 529 hospitals approved by Japan Society of Anes-
thesiology. Masui. 1992;41(11):1825–31.
Funding  This study was supported by the Gunma Foundation for Med- 9. Hopkins PM, Cooke PJ, Clarke RC, Guttormsen AB, Platt PR,
icine and Health Science, and the Japan Society for the Promotion of Dewachter P, Ebo DG, Garcez T, Garvey LH, Hepner DL, Khan
Science KAKENHI 18K08809. DA, Kolawole H, Kopac P, Kroigaard M, Laguna JJ, Marshall SD,
Mertes PM, Rose MA, Sabato V, Savic LC, Savic S, Takazawa
Compliance with ethical standards  T, Volcheck GW, Voltolini S, Sadleir PHM. Consensus clinical
scoring for suspected perioperative immediate hypersensitivity
Conflict of interests  The authors declare that they have no conflicts reactions. Br J Anaesth. 2019;123(1):e29–37.
of interest. 10. Horiuchi T, Yokohama A, Orihara M, Tomita Y, Tomioka A,
Yoshida N, Takahashi K, Saito S, Takazawa T. Usefulness of
basophil activation tests for diagnosis of Sugammadex-induced
anaphylaxis. Anesth Analg. 2018;126(5):1509–16.

13
Journal of Anesthesia

11. Horiuchi T, Takazawa T, Orihara M, Sakamoto S, Yokohama 16. Takazawa T, Mitsuhata H, Mertes PM. Sugammadex and rocuro-
A, Takahashi J, Tomioka A, Yoshida N, Hagiwara K, Saito S. nium-induced anaphylaxis. J Anesth. 2016;30(2):290–7.
Required cefazolin concentration to maximize diagnostic accuracy 17. Sadleir PH, Clarke RC, Bunning DL, Platt PR. Anaphylaxis
of the basophil activation test for cefazolin-induced anaphylaxis. to neuromuscular blocking drugs: incidence and cross-reac-
J Anesth. 2018;32(6):797–805. tivity in Western Australia from 2002 to 2011. Br J Anaesth.
12. Takazawa T, Tomita Y, Yoshida N, Tomioka A, Horiuchi T, 2013;110(6):981–7.
Nagata C, Orihara M, Yamada MH, Saito S. Three suspected cases 18. Kroigaard M, Garvey LH, Menne T, Husum B. Allergic reactions
of sugammadex-induced anaphylactic shock. BMC anesthesiol- in anaesthesia: are suspected causes confirmed on subsequent test-
ogy. 2014;14:92. ing? Br J Anaesth. 2005;95(4):468–71.
13. Orihara M, Takazawa T, Horiuchi T, Sakamoto S, Nagumo K, 19. Horiuchi T, Takazawa T, Saito S. A case of Rocuronium-induced
Tomita Y, Tomioka A, Yoshida N, Yokohama A, Saito S. Com- anaphylaxis in which surgery was subsequently performed under
parison of incidence of anaphylaxis between sugammadex and general anesthesia without neuromuscular blocking agents. Masui.
neostigmine: a retrospective multicentre observational study. Br 2016;65(3):299–303.
J Anaesth. 2020;124(2):154–63.
14. Takahashi M, Hotta K, Inoue S, Takazawa T, Horiuchi T, Iga- Publisher’s Note Springer Nature remains neutral with regard to
rashi T, Takeuchi M. Mepivacaine-induced anaphylactic shock jurisdictional claims in published maps and institutional affiliations.
in a pregnant woman undergoing combined spinal and epidural
anesthesia for cesarean delivery: a case report. JA Clin Rep.
2019;5(1):84.
15. Ring J, Messmer K. Incidence and severity of anaphylactoid reac-
tions to colloid volume substitutes. Lancet. 1977;1(8009):466–9.

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