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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 multi-centre studies are necessary to determine indications and establish common testing protocols.

Perioperative immediate hypersensitivity reactions are rare. Subsequent allergy investigation is complicated by multiple simultaneous drug exposures, the use of drugs with potent effects and the many differential diagnoses to hypersensitivity in the perioperative setting. The approach to the investigation of these complex reactions is not standardized, and it is becoming increasingly apparent that collaboration between experts in the field of allergy/immunology/dermatology and anaesthesiology is needed to provide the best possible care for these patients. The EAACI task force behind this position paper has therefore combined the expertise of allergists, immunologists and anaesthesiologists. The aims of this position paper were to provide recommendations for the investigation of immediate-type perioperative hypersensitivity reactions and to provide practical information that can assist clinicians in planning and carrying out investigations.

Background Neuromuscular blocking agents (NMBAs) are the main agents involved during perioperative immediate hypersensitivity. The etiological diagnosis (IgE-mediated allergy vs nonallergy) is linked to the clinical presentation together with tryptase and histamine levels and skin test results. The role of basophil activation test (BAT) needs to be better defined in this setting. Objectives To assess the role of BAT compared with the results of skin testing in 31 patients experiencing immediate NMBA hypersensitivity and compare skin test results and BAT performances in the identification of alternative NMBAs. Methods Histamine and tryptase levels were quantified. Anesthetic drugs, including NMBAs, were skin-tested. Basophil CD63 and CD203c expressions were measured in response to serial dilutions of the different NMBAs. Results Allergy and Nonallergy groups involved 19 and 12 patients, respectively. Circulating histamine and tryptase levels were significantly increased in allergic patients. In the Allergy group, while skin test results were positive in 100% (19 of 19) of the cases, BAT positivity to the culprit NMBA reached 78.9% (15 of 19) when combining CD63 and CD203c. NMBAs cross-reactivity was identified through skin testing and BAT in 36.8% (7 of 19) and 26.3% (5 of 19) of the cases, respectively. The concordance (culprit and cross-reactive NMBAs) between skin tests and BATs was between 73.6% (14 of 19) and 100% (19 of 19) for each NMBA. Negative skin-tested NMBAs were uneventfully used in 7 NMBA-allergic patients. In the Nonallergy group, skin test results were negative in 100% of the cases while BAT result was positive once (CD63 upregulation). Conclusion In our technical conditions, BAT does not replace skin testing in the assessment of NMBA allergy.

This narrative review seeks to distinguish the clinical patterns of pre-existing allergic conditions from other confounding non-allergic clinical entities, and to identify the potential related risks and facilitate their perioperative management. Follow-up investigation should be performed after a perioperative immediate hypersensitivity to establish a diagnosis and provide advice for subsequent anaesthetics, the main risk factor for perioperative immunoglobulin E (IgE)-mediated anaphylaxis being a previous uninvestigated perioperative immediate hypersensitivity reaction. The concept of cross-reactivity between drugs used in the perioperative setting and food is often quoted, but usually not supported by evidence. There is no reason to avoid propofol in egg, soy, or peanut allergy. The allergenic determinants have been characterised for fish, shellfish, and povidone iodine, but remain unknown for iodinated contrast agents. Iodinated drugs may be used in seafood allergy. Evidence supporting the risk for protamine allergy in fish allergy and in neutral protamine Hagedorn insulin use is lacking. Conversely, cross-reactivity to gelatin-based colloid may occur in α-gal syndrome. Atopy and allergic asthma along with other non-allergic conditions, such as NSAID-exacerbated respiratory disease, chronic urticaria, mastocytosis, and hereditary or acquired angioedema, are not risk factors for IgE-mediated drug allergy, but there is a perioperative risk associated with the potential for exacerbation of the various conditions.

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.

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.

Background: Grading schemes for severity of suspected allergic reactions have been applied to the perioperative setting, but there is no scoring system that estimates the likelihood that the reaction is an immediate hypersensitivity reaction. Such a score would be useful in evaluating current and proposed tests for the diagnosis of suspected perioperative immediate hypersensitivity reactions and culprit agents. Methods: We conducted a Delphi consensus process involving a panel of 25 international multidisciplinary experts in suspected perioperative allergy. Items were ranked according to appropriateness (on a scale of 1-9) and consensus, which informed development of a clinical scoring system. The scoring system was assessed by comparing scores generated for a series of clinical scenarios against ratings of panel members. Supplementary scores for mast cell tryptase were generated. Results: Two rounds of the Delphi process achieved stopping criteria for all statements. From an initial 60 statements, 43 were rated appropriate (median score 7 or more) and met agreement criteria (disagreement index

We report a case of transient symptomatic transferred IgE-mediated peanut allergy after elective blood-group compatible liver transplantation. We show that the allergy was transient and therefore passive, authorizing further uneventful peanut consumption. Skin tests with commercial peanut extract and native peanut were performed in the recipient. Circulating specific IgE against peanut and recombinant peanut allergens (rArah1, rArah2, rArah3) was measured in stored serum samples collected from the recipient between 6 months before and 8 months after liver transplantation. Specific IgE levels in the donor were measured at the time of multiorgan donation. In the recipient, diagnosis of IgE-mediated peanut anaphylaxis was based on the clinical history and detection of specific IgE against peanut and recombinant major peanut allergens (rArah1, rArah2 and rArah3). Skin tests were negative and specific IgE undetectable 6 months after the clinical reaction. Oral peanut challenge was negative excluding persistent peanut allergy. This case confirms that IgE-mediated peanut allergy can be transferred by liver transplantation and shows that it may be transient and therefore passively acquired.

During the preoperative evaluation, patients frequently indicate 'multiple drug allergies', most of which have not been validated. Potential allergic cross-reactivity between drugs and foods is frequently considered as a risk factor for perioperative hypersensitivity. The aim of this review is to facilitate the recognition of risk factors for perioperative anaphylaxis and help the management of patients with 'multiple drug allergies' during the perioperative period.Neuromuscular blocking agents (NMBAs) and antibiotics are the most common drugs triggering perioperative anaphylaxis. Quaternary ammonium ions have been suggested to be the allergenic determinant of NMBAs. Even though the 'pholcodine hypothesis' has been suggested to explain the occurrence of NMBA-induced allergy, this concept remains unclear. Although many practitioners believe that certain food allergies present an issue with the use of propofol, there is no role to contraindicate propofol in egg-allergic, soy-allergic or peanut-allergic patients. IgE-mediated hypersensitivity has been reported with seafood and iodinated drugs, IgE-mediated hypersensitivity has been reported with seafood and iodinated drugs, but there is no cross-reactivity between them. The allergenic determinants have been characterized for fish, shellfish and povidone iodine and remain unknown for contrast agents.There are many false assumptions regarding drug allergies. The main goal of this article is to review the potential cross-reactivity among specific families of drugs and foods in order to facilitate the anesthetic management of patients with 'multiple drug allergies'.

We report a case of drug-induced immediate hypersensitivity occurring after atracurium injection in a patient with cutaneous mastocytosis.A 69-yr-old woman was scheduled for hysterectomy. She was premedicated with hydroxyzine, and anesthesia was induced with sufentanil, propofol, and atracurium. Within two to three minutes following the injection of atracurium, the patient experienced an episode of generalized erythema and arterial hypotension associated with tachycardia. No bronchospasm was observed. Her cardiovascular signs resolved spontaneously within five minutes, while her cutaneous signs disappeared within 30 min. Anesthesia and surgery remained uneventful. The patient's serum tryptase levels were measured at different time points following the clinical reaction. An in vitro flow cytometry-based basophil activation test was performed with atracurium, and in vivo skin tests to latex and all drugs which were administered just before the clinical reaction were also done. The serum tryptase showed increased concentrations that remained elevated for 24 hr, 48 hr, and even four weeks after the clinical reaction. Atracurium did not induce either CD63 or CD203c upregulation, and the skin tests were negative in response to the medications received (propofol, sufentanil, and atracurium) as well as to latex.Allergic hypersensitivity to atracurium was ruled out. Increased tryptase concentrations following the clinical reaction, persistent increased levels of basal serum tryptase, and negative skin tests suggested the onset of mast cell degranulation in a patient with mastocytosis. Immediate reaction occurring in patients with mastocytosis should be investigated in order to identify the mechanism of the reaction, either histamine release due to the disease itself or due to a concurrent drug/agent-induced IgE-mediated mechanism.

Apical ballooning syndrome, a reversible left ventricle dysfunction, has been reported following anaphylaxis and, during this clinical circumstance, is seemingly linked to the use of either low or high doses of epinephrine. We report a severe succinylcholine-induced IgE-mediated anaphylaxis in a 65-year-old woman, in whom the diagnosis of apical ballooning syndrome following anaphylaxis was established. As a thorough description of the clinical features and resuscitative measures could be obtained, we discuss the reasons for apical ballooning syndrome occurrence and highlight the fact that optimal care management of anaphylaxis should include a progressive titration of epinephrine.

Perioperative anaphylaxis is a unique condition as a result of the additive cardiovascular effects of anesthetics on the cardiovascular disturbances of anaphylaxis. It occurs mainly in adulthood, primarily follows anesthetic induction, and for the most part, is an IgE-mediated pathomechanism. Neuromuscular blocking agents (NMBAs) and antibiotics are the main culprit drugs, while latex is now infrequently involved. The Ring and Messmer scale is a useful tool for demonstrating the clinical severity of perioperative immediate hypersensitivity and guiding its management. Grades III and IV are life-threatening and are referred to as anaphylaxis. Three different clinical patterns of grade III may be observed, where cardiovascular collapse is the cardinal sign. Grade IV presents as cardiac arrest. The initial diagnosis is presumptive, whereas the etiological assessment is linked to the clinical presentation, tryptase levels, and skin test results. Since anaphylaxis presents with significant hypovolemia and vasoplegia, aggressive fluid therapy and epinephrine are the cornerstones of management. Whenever possible, anesthetic discontinuation is also recommended. Scientific evidence in favor of preemptive therapeutic strategies to prevent anaphylaxis in the operative setting is lacking.

BACKGROUND: Artificial oxygen carriers such as perfluorocarbon (PFC) emulsions have reached Phase III clinical trials as alternatives to homologous blood, but their rheologic effects have not been characterized. In this study, the rheologic effects of PFC emulsion in the presence of clinically used volume expanders were investigated. STUDY DESIGN AND METHODS: The effects of a new PFC emulsion (small droplet size with narrow size distribution) at two PFC concentrations (4 and 8 g/dL) on plasma and whole-blood viscosity in the presence of human albumin solution (HAS), hydroxyethyl starch (HES), or modified fluid gelatin (MFG) were investigated. Three hematocrit (Hct) levels were investigated: 30, 20, and 13 percent. Plasma, PFC emulsions, and whole-blood viscosity, with a Couette viscometer, and RBC elongation, with an ektacytometer, were measured for shear rates of 0.2 to 128 per second. RESULTS: The two PFC concentrations increased plasma and whole-blood viscosities. Viscosity values similar to physiologic ones (Hct level, 40%) were observed at: 1) Hct level of 13 percent, with 4 or 8 g per dL MFG-PFC; 2) Hct level of 20 percent, with 4 g per dL MFG-PFC; and 3) Hct level of 30 percent, with 4 g per dL HES-PFC and 4 and 8 g per dL HAS-PFC. RBC deformability was unchanged. CONCLUSION: It is concluded that this new PFC emulsion increases plasma and blood viscosity and that among the three studied volume expanders, the interaction with MFG can result in viscosity values above the physiologic one even at low Hct values. The possible consequences of the increased viscosity at low Hct values are discussed.

Methylene blue-treated fresh-frozen plasma (MB-FFP) is mainly used in Europe. The advantage of the methylene blue system is that units can be treated individually. The combined action of methylene blue and illumination is a photodynamic process preventing viral RNA and DNA replication. We report the first immediate allergic hypersensitivity reaction to methylene blue-treated plasma transfusion. The clinical course and subsequent assessment of the allergic reaction, including skin tests and basophil activation test, confirmed methylene blue-induced IgE-mediated anaphylaxis. All immediate reactions after MB-FFP transfusion should be investigated to document the underlying mechanism.

"Iodine allergy" does not exist. The concept of "iodine allergy" should be abandoned since it may result in inappropriate measures such as drug, food or environmental eviction. Immediate or non-immediate allergic hypersensitivity to iodinated contrast media is not infrequent. The corresponding allergens have not been identified. Iodine is not involved. Immediate or non-immediate allergic hypersensitivity to povidone iodine is rare. The corresponding allergen is povidone in case of immediate hypersensitivity while nonoxynol might be involved during non-immediate hypersensitivity. Seafood allergens belong to a group of muscle proteins. Immediate drug hypersensitivity or food hypersensitivity is assessed by immediate-reading skin tests while non-immediate drug hypersensitivity is investigated by delayed-reading skin testing. Combined histamine and tryptase measurement is invaluable during the diagnostic approach of immediate hypersensitivity. Other biological tests are being evaluated. Allergic hypersensitivity to iodinated contrast agents does not contraindicate the use of other iodinated drugs.

The prevalence of anaphylaxis occurring during pregnancy is approximately 3 cases per 100,000 deliveries. The management of anaphylaxis occurring during the third trimester of pregnancy may be challenging because of the additive effects of aortocaval compression and cardiovascular disturbances of anaphylaxis. In this review, we identify the clinical signs of anaphylaxis occurring during labor and cesarean delivery, discuss the more common allergens that cause anaphylaxis during this clinical setting, and develop a rational approach to the identification of the offending allergen. We also suggest strategies for the management of anaphylaxis occurring during the third trimester of pregnancy, including the prompt administration of epinephrine and emergency cesarean delivery in cases of severe reactions. Evidence is limited to case reports and extrapolation from nonfatal and fatal cases, interpretation of pathophysiology, and consensus opinion.

This article has been selected for the ANESTHESIOLOGY CME Program. Learning objectives and disclosure and ordering information can be found in the CME section at the front of this issue.

Objectives To investigate the pathomechanisms involved in cases of immediate hypersensitivity reactions occurring after the administration of iodinated contrast media. Materials and methods Patients having presented clinical signs of immediate hypersensitivity suggesting allergy after iodinated contrast medium were investigated. Histamine and tryptase concentrations were measured, and/or skin tests were performed. Patients with positive skin tests to the culprit contrast agent were classified as IgE-mediated allergic hypersensitivity (Group I) and patients with negative skin tests as non-allergic hypersensitivity (Group II). Results 38 patients were included. Most reactions appeared after non-ionic (n = 32). Reactions were more frequently severe following ionic than non-ionic (p = 0.014). Skin testing was not performed in 11 patients. Skin tests with the culprit contrast agent were negative in 26% of the patients (Group II, n = 7) whereas they were found positive with the contrast agent in 73% of the patients (Group I, n = 19). Latex-induced reaction was diagnosed in one patient, and was consequently excluded from the cohort. In Group I, the frequency of cross-reactivity with the other commercialized iodinated contrast media was low (7%). Cardiovascular signs were present in Group I (52.6%, n = 10), and absent in Group II (p = 0.023). Histamine and tryptase concentrations were higher in patients who had cardiovascular signs (p Conclusion Immediate reactions with clinical signs suggesting allergy along with positive skin tests with the administered contrast agent confirm immediate allergic hypersensitivity (anaphylaxis) to this agent. Consequently, the culprit contrast agent should be definitely avoided as well as cross-reactive ICM in order to prevent further recurrences.

Purpose of review Anaphylactic reactions occurring during anaesthesia may be life threatening. Lethal issues may be involved in up to 3-10% of the cases. The allergological assessment (including biochemical tests and skin tests) is the key to the management of these reactions. The scope of this review is to focus on the allergological assessment required to prove the immune mechanism, to identify the culprit drug or substance and the cross-reactive molecules, especially for neuromuscular blocking agents, allowing preventive measures for future anaesthetic procedures. Recent findings To describe the allergological assessment (including biochemical tests and skin tests performed according to the current guidelines) in order to prove the immune mechanism as the responsibility of the culprit allergen. The most frequent and less frequent drugs involved are described. The different biological tools available are detailed. To ensure an accurate diagnosis, the interpretation of the allergological assessment should be linked to the description of the clinical events as their time onset following the injection/administration of the suspected drug(s)/substance. Summary To describe the different tools (biochemical tests and skin tests) available in order to prove the diagnosis of an anaphylactic reaction occurring during anaesthesia.

Bariatric surgery is increasingly performed for effective weight loss. A morbidly obese 27-year-old woman underwent laparoscopoic adjustable gastric banding. After a postoperative adjustment of the stomal diameter of the band with ioxaglate, she presented an immediate hypersensitivity reaction. With the patient's consent, cutaneous tests to contrast agents used during the procedure and to latex were performed. Allergy to ioxaglate was confirmed by skin-test positivity. This case suggests the need for allergological investigation of drugs/substances administered during the perioperative period, in case of hypersensitivity reaction.

Background: We report a documented grade III IgE-mediated hypersensitivity reaction associated with the use of 2.5% patent blue V dye for sentinel lymph node biopsy during breast cancer surgery. Methods: Immediately after the reaction, when hemodynamic stability was obtained, plasma histamine was measured whereas serum tryptase was not. Six weeks later, with the patient's consent, cutaneous tests to patent blue V dye, methylene blue dye, latex and all drugs used during surgery were performed according to standardized procedures. Results and conclusion: Clinical symptoms, biological assessment results and cutaneous tests positivity confirmed the onset of an anaphylactic reaction due to patent blue V. Of interest, the positivity of the cutaneous tests observed with patent blue V was not found with methylene blue which might be proposed for further investigations in our patient. This case report confirms the need for systematic allergological investigation of all drugs and substances administered during the peri-operative period in case of an immediate hypersensitivity reaction occurring during anesthesia.

We report a documented severe immunoglobulin E-mediated hypersensitivity reaction associated with use of 1% methylene blue for detection of tubal permeability occurring during general anesthesia. Clinical symptoms, biological assessment results, and cutaneous test positivity confirmed an anaphylactic reaction to methylene blue. This case report confirms the need for systematic allergological investigation of all drugs and substances administered during the perioperative period in the event of a hypersensitivity reaction occurring during anesthesia. Anesthesiologists should be aware of the possibility of hypersensitivity reactions involving any drug or substance used during surgery.

Immediate allergic hypersensitivity reactions with fentanyl are rarely reported. We diagnosed a presumably IgE-mediated allergic hypersensitivity reaction comprising generalized erythema and bronchospasm 4 h after the first-time application of transdermal fentanyl. Prick test remained negative with fentanyl whereas an intradermal test (IDT) with fentanyl was positive (dilution 10(-2)). Cross-reactivity was found with sufentanil but not with remifentanil. The diagnosis was supported by the clinical history and a positive IDT with fentanyl. This case report confirms the need for a systematic allergological investigation in case of immediate hypersensitivity reactions for all drugs and all modes of administration.