Abstract
Background
Perioperative anaphylaxis (POA) is a life-threatening condition with substantial variability in evaluation and management practices.
Objective
To assess current practices, perceived barriers, and regional differences in POA management among allergists worldwide.
Methods
A cross-sectional online survey was distributed to World Allergy Organization (WAO) members from March to June 2024. The 39-question survey addressed demographics, clinical practices, diagnostic tools, perceived challenges, and future needs.
Results
A total of 249 respondents from 50 countries completed the survey (median age 49 years, 49% female, 94% allergists, and 57% with >15 years of clinical experience). While 70% had access to acute serum tryptase (sAT), only 46% obtained it within the recommended 2-h window. Guideline adherence was low: 63% did not perform skin testing 4–6 weeks post-reaction, and fewer than half routinely tested for latex or chlorhexidine. Regional differences were observed: routine latex and chlorhexidine testing was most common in Europe and United States/Canada and least frequent in Africa and Asia (p = 0.0001); tryptase availability was lower in Africa and Latin America. Most respondents identified a culprit in <65% of cases, with antibiotics reported most frequently in Europe and United States/Canada, followed by neuromuscular blocking agents and non-steroidal anti-inflammatory drugs (NSAIDs). Major barriers included limited access to anesthesia records, testing reagents, and resource-related contrainsts in low-income regions. Respondents expressed the need for guidelines on alternative agents and validated non-irritating skin test concentrations.
Conclusions
This international survey highlights substantial regional differences and global barriers in POA evaluation. Improving access to diagnostic resources, enhancing interdisciplinary collaboration, and providing clear guidance on alternative agents and standardized testing methods are essential to optimize worldwide POA management.
Keywords: Anaphylaxis, Perioperative care, Tryptases, Surveys and questionnaires, Allergy and immunology
Introduction
Perioperative anaphylaxis (POA) is a rare but serious condition, with an estimated incidence ranging from 1 in1,250 to 1 in 18,600 per procedures.1 Evaluating and managing POA remains complex. Although drug challenge remains the diagnostic gold standard, clinicians cannot safely perform it for many perioperative medications.2, 3, 4 Skin testing aids in the evaluation of IgE-mediated reactions but remains formally validated only for penicillin.5 Contemporary POA guidelines nevertheless recommend testing all potential culprit agents, including frequently overlook triggers such as chlorhexidine and latex.6, 7, 8 Additional in vitro assays, including serum-specific IgE, basophil activation tests, are promising but remain limited by low precision.2, 3, 4,9 Geographic epidemiologic variations further complicate diagnostic and management practices. Common POA agents include neuromuscular blocking agents (NMBAs) (especially rocuronium and succinylcholine), antibiotics (eg, cefazolin, teicoplanin), blue dyes, chlorhexidine, and less commonly, sugammadex and latex, with regional and temporal variation in frequency.10 Paired measurement of serum acute tryptase (sAT) and baseline tryptase (sBT) using formula 1.2 x sBT + 2 ng/mL to improves diagnostic accuracy,11 demonstrating a positive predictive value of 94%, negative predictive value of 53%, sensitivity of 75%, and specificity of 86% for POA.12 Understanding regional differences in diagnostic and management practices, as well as allergists’ perceptions of these challenges, remain essential to improve patients outcomes.
The World Allergy Organization (WAO) represents 115 regional and national allergy and clinical immunology societies worldwide. We conducted a cross-sectional online survey of WAO members to assess current practices in POA evaluation and management, with the aim of characterizing respondents demographic characteristics, practices patterns, and perceived barriers to care.
Materials and methods
We conducted a cross-sectional online survey of WAO members using a snowball sampling strategy between March and June 2024. The survey comprised 39 questions in total, including 31 single-response questions (5 yes/no and 26 multiple-choice), 5 multiple-response multiple-choice questions, and 2 open-ended questions. The questions were categorized into demographics, evaluation and management, perceived barriers, and future directions (see online repository supplemental material survey). members using a snowball developed the study protocol and questionnaire to address current knowledge gaps. Committee members reviewed 2 successive iterations of the survey, and the Committee approved the final version in 2023. The survey was approved by the WAO Anaphylaxis Committee and Board of Directors on 2023 and January 2024. The online version of the questionnaire was made available in English using Google forms.
The survey captured demographics, clinical experience, and POA evaluation practices, including tryptase testing, culprit identification, skin testing, anesthesia record access, high-risk patients’ assessment, NMBA challenges, joint allergy-anesthesia clinic availability, and perceived common POA triggers (see Table 1, Table 2, Table 3 for full details). For each culprit agent, a weighted mean rank was calculated by multiplying the number of responses at each rank by the corresponding rank value, summing the products, and dividing by the total number of responses. Finally, respondents were asked about their perceived challenges for POA evaluation, the factors that could make them more confident in their POA evaluations, and things that they would include in future POA WAO guidelines.
Table 1.
Characteristics of survey respondents.
| Variable | n (%) |
|---|---|
| Age, median (IQR) | 49 (19) |
| Gender | |
| Female | 121 (49) |
| Male | 123 (49) |
| Non-binary | 1 (0) |
| Prefer not to disclose | 4 (2) |
| Specialty | |
| Allergist | 236 (94) |
| Anesthesiologist | 7 (3) |
| Other | 6 (2) |
| Clinical experience, years | |
| <5 | 32 (13) |
| 6-9 | 30 (12) |
| 10-14 | 44 (18) |
| 15-20 | 33 (13) |
| >20 | 110 (44) |
| POA evaluations per year | |
| 0 | 16 (7) |
| 1-5 | 114 (46) |
| 6-10 | 51 (21) |
| 11-15 | 29 (12) |
| >15 | 39 (16) |
IQR: Interquartile range; POA: Perioperative anaphylaxis
Table 2.
Tryptase in POA evaluations.
| Variable | n (%) |
|---|---|
| Tryptase available in practice | 249 |
| Yes | 175 (70) |
| No | 74 (30) |
| Absolute sAT cut-off limit | 188 |
| >8 ng/mL | 18 (10) |
| >11.5 ng/mL | 95 (51) |
| >15 ng/mL | 21 (11) |
| >25 ng/mL | 10 (5) |
| Other | 44 (23) |
| Comparison of sAT with sBT | 190 |
| Yes | 175 (92) |
| No | 15 (8) |
| sAT/sBT formula use | 175 |
| Acute tryptase >1.2 x baseline tryptase + 2 ng/mL | 156 (89) |
| A 1.68 ratio in patients with HAT or systemic mastocytosis | 4 (2) |
| A ratio of sAT/sBT of 1.685 if baseline tryptase is elevated | 8 (5) |
| Other | 7 (4) |
| Tryptase obtained within 2 h of the event | 189 |
| >80% of time | 27 (14) |
| 61–80% of time | 21 (11) |
| 41–60% of time | 19 (10) |
| 20–40% of time | 28 (15) |
| <20% of time | 88 (46) |
| Never | 7 (4) |
| Evaluating HAT in elevated sBT | 242 |
| Yes | 86 (36) |
| No – genotyping not available | 128 (53) |
| No – if the tryptase level is explained by chronic renal failure or myeloid disease | 13 (5) |
| No – irrespective of genotyping | 15 (6) |
POA: Perioperative anaphylaxis; sAT: Serum acute tryptase; sBT: Serum baseline tryptase.
HAT: Hereditary alpha tryptasemia
Table 3.
POA guideline adherence.
| Variable | n (%) |
|---|---|
| Timing of skin testing | 249 |
| Within 1 week of reaction | 4 (1) |
| 1–2 weeks of reaction | 12 (5) |
| 2–4 weeks of reaction | 19 (7) |
| 4–6 weeks of reaction | 91 (37) |
| 6–8 weeks of reaction | 46 (19) |
| 2–3 months of reaction | 24 (10) |
| >3 months of reaction | 53 (21) |
| Obtain anesthesia record | 249 |
| <25% of time | 67 (27) |
| 26–50% of time | 31 (13) |
| 51–75% of time | 32 (13) |
| 76–95% of time | 62 (25) |
| Always | 57 (23) |
| Test for chlorhexidine and latex | 249 |
| <25% of the time | 69 (28) |
| 26–50% of the time | 22 (9) |
| 51–75% of the time | 20 (8) |
| 76–95% of the tie | 33 (13) |
| Always | 105 (42) |
| NMBA challenges | 249 |
| No | 211 (85) |
| Yes | 38 (15) |
| Joint allergy-anesthesia clinic for POA evaluation | 249 |
| No | 197 (79) |
| Yes | 52 (21) |
POA: Perioperative anaphylaxis
The survey was beta-tested and sent out to WAO members. It was open to receive responses between March 5, 2024 and May 2, 2024 with a single reminder on March 28, 2024. The survey participation was voluntary and anonymous. We analyzed responses using frequencies and percentages for categorical data and median with interquartile range (IQR) for continuous variables. We acknowledge that subgroup analysis by geographic region must be interpreted cautiously, as large differences in practice patterns can result in many statistically significant findings that may not be clinically meaningful. To balance rigor with interpretability, we limited inferential analyses and performed a chi-square test with Monte Carlo simulation only for prespecified variables of interest, including guideline adherence (routine testing for latex/chlorhexidine and timing of skin testing), tryptase availability, and identification of a causal agent. Data was analyzed using Excel and R studio version 2023.12.1 + 402 (R Foundation for Statistical Computing, Vienna, Austria).
Results
Demographic characteristics
We received responses from 249 participants representing 50 countries across all continents except Antarctica (see online repository supplemental material survey). The USA (13%), Brazil (9%), Italy (9%), and Mexico (7%) had the highest number of survey responses (Fig. 1). The median age of respondents was 49 years (IQR: 19), 121 (49%) were female, 236 (94%) were allergists, and 143 (57%) had more than 15 years of experience. The demographic characteristics of respondents are presented in Table 1.
Fig. 1.
Geographical representation of respondents. 249 responses were received from 50 countries. Top response regions included USA, Brazil, Italy, and Mexico
Tryptase
When a serum tryptase was available (70%), most participants (89%) used the sAT >1.2 x baseline tryptase + 2 ng/ml formula to determine MCA. On the other hand, approximately half of the participants (51%) used 11.5 ng/mL as the cut-off for a positive sAT. Additionally, 46% reported obtaining tryptase levels in fewer than 20% of cases, and most (64%) did not assess for HAT when sBT was elevated (Table II).
Allergy testing
The majority of participants did not conduct skin testing 4–6 weeks after the initial reaction (63%). Only a small proportion routinely obtained anesthesia records (23%), included latex and chlorhexidine testing (42%), performed NMBA challenges (15%), or operated a joint allergy-anesthesia clinic (21%) as part of POA evaluations (Table III).
Allergy evaluation outcomes
Most respondents reported finding a culprit less than 65% of the time, as shown in Table IV. When a causal agent was identified (Fig. 2), most perceived antibiotics as the main culprit (mean rank 2.3), followed by NMBAs (mean rank 2.5) and NSAIDs (mean rank 3.9), with lower scores reflecting higher perceived frequency. Discussions with an anesthesiologist or surgeon who was present at the time of the event were infrequent (Table IV). The majority of respondents had less than 5 high-risk surgery consults annually, and a set checklist for evaluation and management of POA was not available in most cases. Routine reporting of POA in an institutional, regional, national, or international registry was 1–17% (Table IV).
Table 4.
Evaluation and management.
| Variable | n (%) |
|---|---|
| POA culprit identification frequency | 249 |
| <20% | 56 (22) |
| 21–35% | 40 (16) |
| 36–50% | 39 (16) |
| 51–65% | 55 (22) |
| 66–85% | 45 (18) |
| >85% | 14 (6) |
| Discussion with anesthesiologist or surgeon present at time of POA event | 249 |
| Never | 28 (11) |
| 1–20% | 91 (37) |
| 21–40% | 25 (10) |
| 41–60% | 25 (10) |
| 61–80% | 17 (7) |
| >80% | 63 (25) |
| Set checklist of evaluation and management of POA in your clinic | 249 |
| Yes | 105 (42) |
| No | 144 (58) |
| Routine recording of POA cases in a registry | 249 |
| No | 180 (72) |
| Yes, in a institutional registry | 42 (17) |
| Yes, in a regional registry | 5 (2) |
| Yes, in a national registry | 20 (8) |
| Yes, in an international registry | 2 (1) |
| High-risk surgery consults in a year | 249 |
| <5 | 141 (57) |
| >30 | 17 (7) |
| 16-20 | 27 (11) |
| 21-30 | 8 (3) |
| 6-15 | 56 (22) |
POA: Perioperative anaphylaxis
Fig. 2.
Most common perceived POA culprits.
Barriers
The top barriers to POA evaluation and management included access to anesthesia records, performing anesthetic challenges, availability of testing reagents, and close-loop communication with anesthesia (Table V). Provider confidence would improve if testing was validated and the ability to perform anesthetic challenges was strengthened. Respondents believe that future guidelines should focus on alternative agents should be chosen based on negative skin testing results or challenges when feasible,13 and on non-irritating skin test concentrations of perioperative medications (Table V).
Table 5.
Challenges and perceptions of survey respondents
| Variable | n (%) |
|---|---|
| Challenges in POA evaluation | n = 674 |
| Access to operative report/anesthesia record and details of the surgery | 154 (23) |
| Performing anesthetic challenges | 141 (21) |
| Obtaining agents to test to | 124 (18) |
| Ability/time to talk with the anesthesiologist | 107 (16) |
| No access to biomarkers (ie, tryptase) | 80 (12) |
| Biomarkers (ie, tryptase) are available but they are cost-prohibited | 45 (7) |
| No expertise in the field | 23 (3) |
| What would help you feel more confident in your evaluation of perioperative anaphylaxis? | n = 1054 |
| Ability to perform anesthetic challenges | 236 (22) |
| Validation of testing | 228 (22) |
| Further education | 206 (20) |
| Tryptase levels obtained at the time of event | 196 (19) |
| Practice parameter or guideline | 148 (14) |
| Ability to perform anesthetic challenges | 40 (4) |
| What would you include in POA WAO guidelines? | n = 1003 |
| Information regarding alternative agents in the setting of positive testing | 169 (17) |
| Non-irritating skin test concentrations of medications used perioperatively | 166 (17) |
| Information regarding alternative agents in the absence of positive testing | 153 (15) |
| Management of patients with concomitant mastocytosis | 139 (14) |
| Timing of reaction in relationship to administration of medications | 139 (14) |
| Prevalence data for agents causing perioperative anaphylaxis | 134 (13) |
| Prevalence data for perioperative anaphylaxis | 103 (10) |
Variables by continent
Practices varied by continent (Table VI). Routine testing for latex and chlorhexidine differed markedly across regions (p = 0.0001), with “always” testing reported most frequently in Europe, Latin America, and Oceania, and least often in Africa and Asia. The timing of skin testing showed regional trends but did not reach statistical significance (p = 0.08), with most respondents performing testing at 4–6 weeks after the reaction. Tryptase availability did not differ significantly by continent (p = 0.49), although access was lowest in Africa and highest in Europe, US/Canada, and Oceania.
Table 6.
Analysis of Characteristics of interest by continent.
| Characteristic | Africa n = 9 (%) | Asia n = 29 (%) | Latin America n = 54 (%) | Europe n = 77 (%) | US/Canada n = 28 (%) | Oceania n = 3 (%) | P – value |
|---|---|---|---|---|---|---|---|
| Testing to latex and chlorhexidine | 0.0001 | ||||||
| <25% of time | 3 (33) | 13 (45) | 13 (24) | 10 (13) | 10 (36) | 0 (0) | |
| 26–50% of time | 3 (33) | 4 (14) | 5 (9) | 4 (5) | 2 (7) | 0 (0) | |
| 51–75% of time | 0 (0) | 2 (7) | 2 (4) | 9 (12) | 5 (18) | 0 (0) | |
| 76%–95% of time | 1 (11) | 5 (17) | 8 (15) | 11 (14) | 3 (11) | 0 (0) | |
| Always | 2 (22) | 5 (17) | 26 (48) | 43 (56) | 8 (29) | 3 (100) | |
| Timing of skin testing | 0.08 | ||||||
| Within 1 week of reaction | 0 (0) | 1 (3) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | |
| 1–2 weeks of reaction | 1 (11) | 3 (10) | 2 (4) | 2 (3) | 0 (0) | 0 (0) | |
| 2–4 weeks of reaction | 3 (33) | 4 (14) | 4 (7) | 6 (8) | 1 (4) | 0 (0) | |
| 4–6 weeks of reaction | 3 (33) | 14 (48) | 21 (39) | 24 (31) | 14 (50) | 0 (0) | |
| 6–8 weeks of reaction | 2 (22) | 4 (14) | 12 (22) | 13 (17) | 3 (11) | 1 (33) | |
| 2–3 months of reaction | 0 (0) | 2 (7) | 3 (6) | 8 (10) | 5 (18) | 0 (0) | |
| 3 months after reaction | 0 (0) | 1 (3) | 12 (22) | 24 (31) | 5 (18) | 2 (67) | |
| Availability of tryptase | 0.49 | ||||||
| No | 8 (89) | 6 (21) | 32 (59) | 10 (13) | 1 (4) | 0 (0) | |
| Yes | 1 (11) | 23 (79) | 22 (41) | 67 (87) | 27 (96) | 3 (100) | |
| Causal agent | |||||||
| Antibiotic categorya | Africa n = 9 (%) | Asia n = 29 (%) | Latin America n = 54 (%) | Europe n = 77 (%) | US/Canada n = 28 (%) | Oceania n = 3 (%) | 0.01 |
| 1 | 2 (22) | 11 (38) | 17 (31) | 42 (55) | 20 (71) | 2 (67) | |
| 2 | 4 (44) | 9 (31) | 9 (17) | 18 (23) | 7 (25) | 0 (0) | |
| 3 | 0 (0) | 3 (10) | 13 (24) | 4 (5) | 0 (0) | 1 (33) | |
| 4 | 1 (11) | 1 (3) | 5 (9) | 1 (1) | 0 (0) | 0 (0) | |
| 5 | 0 (0) | 2 (7) | 4 (7) | 1 (1) | 1 (4) | 0 (0) | |
| 6 | 2 (22) | 1 (3) | 3 (6) | 2 (3) | 0 (0) | 0 (0) | |
| 7 | 0 (0) | 2 (7) | 3 (6) | 9 (12) | 0 (0) | 0 (0) | |
| Chlorhexidine categorya | Africa n = 9 (%) | Asia n = 29 (%) | Latin America n = 54 (%) | Europe n = 77 (%) | US/Canada n = 28 (%) | Oceania n = 3 (%) | 0.02 |
| 1 | 0 (0) | 3 (10) | 3 (6) | 5 (6) | 1 (4) | 1 (33) | |
| 2 | 0 (0) | 5 (17) | 7 (13) | 8 (10) | 2 (7) | 0 (0) | |
| 3 | 2 (22) | 3 (10) | 8 (15) | 15 (19) | 13 (46) | 2 (67) | |
| 4 | 2 (22) | 5 (17) | 4 (7) | 7 (9) | 5 (18) | 0 (0) | |
| 5 | 0 (0) | 6 (21) | 5 (9) | 16 (21) | 1 (4) | 0 (0) | |
| 6 | 3 (33) | 3 (10) | 16 (30) | 8 (10) | 2 (7) | 0 (0) | |
| 7 | 2 (22) | 5 (17) | 11 (20) | 18 (23) | 4 (14) | 0 (0) | |
| Blue dye categorya | Africa n = 9 (%) | Asia n = 29 (%) | Latin America n = 54 (%) | Europe n = 77 (%) | US/Canada n = 28 (%) | Oceania n = 3 (%) | 0.46 |
| 1 | 1 (11) | 4 (14) | 5 (9) | 9 (12) | 0 (0) | 0 (0) | |
| 2 | 0 (0) | 1 (3) | 5 (9) | 5 (6) | 0 (0) | 1 (33) | |
| 3 | 1 (11) | 3 (10) | 4 (7) | 9 (12) | 1 (4) | 0 (0) | |
| 4 | 0 (0) | 2 (7) | 3 (6) | 3 (4) | 1 (4) | 0 (0) | |
| 5 | 2 (22) | 1 (3) | 4 (7) | 8 (10) | 5 (18) | 1 (33) | |
| 6 | 3 (33) | 2 (7) | 6 (11) | 13 (17) | 3 (11) | 0 (0) | |
| 7 | 2 (22) | 16 (55) | 27 (50) | 30 (39) | 18 (64) | 1 (33) | |
| Hypnotic categorya | Africa n = 9 (%) | Asia n = 29 (%) | Latin America n = 54 (%) | Europe n = 77 (%) | US/Canada n = 28 (%) | Oceania n = 3 (%) | 0.36 |
| 1 | 0 (0) | 3 (10) | 6 (11) | 6 (8) | 0 (0) | 0 (0) | |
| 2 | 0 (0) | 3 (10) | 9 (17) | 6 (8) | 1 (4) | 0 (0) | |
| 3 | 2 (22) | 4 (14) | 9 (17) | 15 (19) | 5 (18) | 0 (0) | |
| 4 | 2 (22) | 0 (0) | 9 (17) | 7 (9) | 4 (14) | 0 (0) | |
| 5 | 3 (33) | 4 (14) | 10 (19) | 12 (16) | 7 (25) | 1 (33) | |
| 6 | 2 (22) | 4 (14) | 5 (9) | 13 (17) | 6 (21) | 1 (33) | |
| 7 | 0 (0) | 11 (38) | 6 (11) | 18 (23) | 5 (18) | 1 (33) | |
| Latex categorya | Africa n = 9 (%) | Asia n = 29 (%) | Latin America n = 54 (%) | Europe n = 77 (%) | US/Canada n = 28 (%) | Oceania n = 3 (%) | 0.02 |
| 1 | 0 (0) | 5 (17) | 11 (20) | 6 (8) | 0 (0) | 0 (0) | |
| 2 | 3 (33) | 1 (3) | 11 (20) | 8 (10) | 2 (7) | 0 (0) | |
| 3 | 1 (11) | 7 (24) | 8 (15) | 11 (14) | 1 (4) | 0 (0) | |
| 4 | 1 (11) | 2 (7) | 10 (19) | 10 (13) | 7 (25) | 1 (33) | |
| 5 | 1 (11) | 4 (14) | 9 (17) | 8 (10) | 5 (18) | 0 (0) | |
| 6 | 2 (22) | 3 (10) | 4 (7) | 14 (18) | 4 (14) | 1 (33) | |
| 7 | 1 (11) | 7 (24) | 1 (2) | 20 (26) | 9 (32) | 1 (33) | |
| NMBA categorya | Africa n = 9 (%) | Asia n = 29 (%) | Latin America n = 54 (%) | Europe n = 77 (%) | US/Canada n = 28 (%) | Oceania n = 3 (%) | 0.44 |
| 1 | 3 (33) | 11 (38) | 20 (37) | 21 (27) | 8 (29) | 1 (33) | |
| 2 | 1 (11) | 7 (24) | 14 (26) | 28 (36) | 11 (39) | 1 (33) | |
| 3 | 2 (22) | 8 (28) | 9 (17) | 8 (10) | 4 (14) | 0 (0) | |
| 4 | 2 (22) | 1 (3) | 4 (7) | 6 (8) | 4 (14) | 0 (0) | |
| 5 | 1 (11) | 0 (0) | 3 (6) | 6 (8) | 1 (4) | 1 (33) | |
| 6 | 0 (0) | 1 (3) | 1 (2) | 7 (9) | 0 (0) | 0 (0) | |
| 7 | 0 (0) | 1 (3) | 3 (6) | 1 (1) | 0 (0) | 0 (0) | |
| NSAID categorya | Africa n = 9 (%) | Asia n = 29 (%) | Latin America n = 54 (%) | Europe n = 77 (%) | US/Canada n = 28 (%) | Oceania n = 3 (%) | 0.03 |
| 1 | 2 (22) | 3 (10) | 7 (13) | 5 (6) | 0 (0) | 0 (0) | |
| 2 | 2 (22) | 5 (17) | 16 (3) | 17 (22) | 1 (4) | 0 (0) | |
| 3 | 1 (11) | 7 (24) | 8 (15) | 13 (17) | 2 (7) | 1 (33) | |
| 4 | 0 (0) | 4 (14) | 11 (20) | 13 (17) | 6 (21) | 1 (33) | |
| 5 | 0 (0) | 5 (17) | 6 (11) | 9 (12) | 5 (18) | 0 (0) | |
| 6 | 1 (11) | 2 (7) | 4 (7) | 13 (17) | 4 (14) | 0 (0) | |
| 7 | 3 (33) | 3 (10) | 2 (4) | 7 (9) | 10 (36) | 1 (33) | |
| Sugammadexa | Africa n = 9 (%) | Asia n = 29 (%) | Latin America n = 54 (%) | Europe n = 77 (%) | US/Canada n = 28 (%) | Oceania n = 3 (%) | 0.81 |
| 1 | 1 (11) | 4 (14) | 7 (13) | 8 (10) | 0 (0) | 0 (0) | |
| 2 | 1 (11) | 2 (7) | 5 (9) | 3 (4) | 0 (0) | 0 (0) | |
| 3 | 0 (0) | 2 (7) | 2 (4) | 7 (9) | 3 (11) | 1 (33) | |
| 4 | 1 (11) | 3 (10) | 1 (2) | 6 (8) | 3 (11) | 0 (0) | |
| 5 | 1 (11) | 1 (3) | 4 (7) | 8 (10) | 3 (11) | 1 (33) | |
| 6 | 1 (11) | 5 (17) | 8 (15) | 10 (13) | 2 (7) | 0 (0) | |
| 7 | 4 (44) | 12 (41) | 27 (50) | 35 (45) | 17 (61) | 1 (33) |
NMBA, neuromuscular blocking agent; NSAID, nonsteroid anti-inflammatory drug.
Perceived order by causal agent when a cause of perioperative anaphylaxis is identified, 1 being most common and the 7 least based on question 11 of the survey
The frequency of identifying specific causal agents varied by continent. Antibiotics were the most commonly reported cause overall, with significant differences across regions, particularly high in US/Canada and Europe. Chlorhexidine also showed regional variation (p = 0.02), being more frequently implicated in Europe and US/Canada. Latex reactions differed significantly by continent as well (p = 0.02), most commonly reported in Europe and US/Canada. In contrast, NMBA, blue dye, hypnotics, and sugammadex did not show statistically significant regional differences, while NSAID reactions varied modestly across continents (p = 0.03). These findings highlight regional differences in perceived or reported POA triggers, with antibiotics, chlorhexidine, and latex showing the greatest variability.
Discussion
This cross-sectional, international survey demonstrates that POA management remains challenging, with low adherence to guideline recommendations, particularly regarding the timing of skin testing and routine evaluation for latex and chlorhexidine. Although tryptase measurement was not universally available, most respondents reported following guideline-based approaches to determine MCA. Physicians identified a culprit agent in approximately half of POA evaluations. When identified, antibiotics were most commonly implicated, followed by NMBAs, NSAIDs, and latex. Limited access to anesthesia records, restricted availability to testing reagents, and challenges in performing anesthetic challenges emerged as major barriers. Respondents also indicated that future WAO POA guidelines should place greater emphasis on non-irritating skin testing concentrations and on guidance for selecting alternative agents, even when a culprit cannot be definitively identified.
Obtaining tryptase levels is crucial, as sAT correlates with the Ring and Messmer severity score, 11,14, 15, 16 aids in endotyping,17 and may help predict whether the culprit agent can be identified through testing.15,16,18 In this survey, 30% of respondents reported that tryptase testing was unavailable, consistent with prior retrospective studies demonstrating incomplete access to this diagnostic tool.19,20 Potential barriers include limited laboratory resources, particularly in low- and middle-income countries, and insufficient awareness of POA among surgical and anesthesia teams. Although current guidelines recommend obtaining sAT within 0.5–2 h of the reaction and baseline level at least 24 h later,6,11 respondents infrequently obtained serum tryptase samples within the recommended timeframe. Tryptase availability were lower in Africa and Latin American compared with Europe, US/Canada, and Oceania, indicating regional resource-related barriers.
Several countries have conducted epidemiological studies of POA. In France, the Groupe d'Etude des Réactions Anaphylactiques Périopératoires (GERAP) network21, 22, 23, 24, 25, 26 has monitored POA epidemiology for 3 decades and reported identification of a culprit agent in approximately 70% of cases, most commonly NMBAs, followed by antibiotics.26 In contrast, studies from the United States report lower culprit is identification rates, ranging from 18% to 57%.15,20,27, 28, 29 Consistent with these findings, respondents in our international survey reported identifying a culprit in roughly half of POA cases. US and European guidelines recommend obtaining serum tryptase levels during evaluations.6,8
Adherence to guideline-recommended diagnostic practices was suboptimal. Only 37% of respondents performed skin testing within the recommended 4–6 weeks following the reaction. Both contemporary US and European guidelines recommend in vivo and in vitro testing for all culprit agents, with a 4–6 week wait time if necessary.6,8 Access to operative and anesthesia records was limited, and fewer than half of respondents reported consistently testing for chlorhexidine and latex. In addition, most respondents did not perform NMBA challenges or have access to joint allergy-anesthesia clinics for POA evaluation. Difficulty obtaining anesthesia records emerged as the most frequently cited barrier, underscoring persistent communication gaps between specialties. Legal and institutional factors influencing access to operative and anesthesia records were not assessed in this survey and should be addressed in future studies. Limited capacity to perform NMBA challenges further constrains comprehensive evaluations.
Respondents emphasized that future POA guidelines should provide clearer recommendations on alternative agents and standardized non-irritating skin test concentrations. Studies have established non-irritating intradermal concentrations for beta-lactam antibiotics,30 NMBAs,31,32 and chlorhexidine,33,34 supporting guideline recommendations for standardized skin testing.6,8 Recent work by Shah et al demonstrates that for chlorhexidine skin testing, sterile water for injection is the preferred diluent for skin prick testing (5 mg/mL) to avoid precipitation, while normal saline can be used for the intradermal concentration (0.002 mg/mL), enabling stable preparation.35 Current literature offers limited guidance on safe alternatives agents following both positive and negative skin test results. A contemporary POA evaluation and management algorithm developed by the European Academy of Allergy and Clinical Immunology (EAACI) is commonly used in the authors’ clinical practice.7
This study has several limitations. Its a survey-based design introduces the potential for recall and self-reporting bias, and voluntary participation may have resulted in selection bias. In addition, the survey may underrepresented non-English speakers and clinicians from low-resource settings or regions with limited WAO engagement, potentially limiting the generalizability of the findings across all healthcare systems.
Overall, this survey highlights substantial global variability and ongoing challenges in the evaluation and management of POA. Addressing diagnostic resource limitations, improving multidisciplinary communication, and expanding access to standardized testing may enhance care consistency. Future international guidelines should prioritize practical recommendations on alternative agents and non-irritating skin testing concentrations to better support clinicians across diverse practice environments. Further studies with broader and more balanced international participation are needed to more accurately characterize global practices in POA management.
Authors’ consent for publication
Yes.
Availability of data and materials
Data will be made available after publication.
Author contributions
Conceptualization: L.T., A.G.-E.; Methodology: R.J.E.-M., V.C., A.S.Y.L.; Investigation: P.A.G., M.E., M.L., G.P.; Data curation: R.J.E.-M.; Formal analysis: R.J.E.-M.; Writing – original draft: R.J.E.-M., A.G.-E.; Writing – review & editing: all authors; Supervision: L.T., P.J.T.; Project administration: L.T.; Resources: M.E., M.L., G.P.; Validation: P.A.G., A.S.Y.L. All authors reviewed and approved the final manuscript.
Ethics statement
This study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki.
Funding
None.
Declaration of interest
The authors declare no competing interests related to the content of this manuscript.
Footnotes
Full list of author information is available at the end of the article
Supplementary data to this article can be found online at https://doi.org/10.1016/j.waojou.2026.101362.
Contributor Information
Mario Morais-Almeida, Email: mmoraisalmeida@netcabo.pt.
Luciana Kase Tanno, Email: luciana.tanno@gmail.com.
Appendix A. Supplementary data
The following is the Supplementary data to this article:
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Data Availability Statement
Data will be made available after publication.