Anaphylaxis during anesthesia in France: An 8-year national survey

doi:10.1016/j.jaci.2011.03.003

Journal of Allergy and Clinical Immunology

Volume 128, Issue 2, August 2011, Pages 366-373

https://doi.org/10.1016/j.jaci.2011.03.003 Get rights and content

Background

More attention should be paid to rare serious adverse events such as anaphylaxis to increase the safety of anesthesia.

Objective

To report the results of an 8-year survey of anaphylaxis during anesthesia in France.

Methods

Data from patients who experienced anaphylaxis between January 1, 1997, and December 31, 2004, were analyzed. Estimated incidences were obtained by combining this database with data from the French pharmacovigilance system by using a capture-recapture method. The number of patients exposed to the offending agents was obtained from data collected during the national survey of anesthesia practice.

Results

A total of 2516 patients was included. A diagnosis of IgE-mediated reaction was established in 1816 cases (72.18%). The most common causes were neuromuscular blocking agents ([NMBAs]; n = 1067; 58.08%), latex (n = 361; 19.65%), and antibiotics (n = 236; 12.85%). The median annual incidence per million procedures was higher for females 154.9 (5th-95th percentile, 117.2-193.1) than for males 55.4 (5th-95th percentile, 42.0-68.0). It reached 250.9 (5th-95th percentile, 189.8-312.9) for women in cases of allergic reactions to NMBAs. In children, a diagnosis of IgE-mediated reactions was obtained in 122 cases (45.9%). The most common causes were latex (n = 51; 41.8%), NMBAs (n = 39; 31.97%), and antibiotics (n = 11; 9.02%). In contrast with adults, no female predominance was observed.

Conclusion

The incidence of allergic reactions during anesthesia, estimated on a national basis, is higher than previously estimated. These results should be taken into account in the evaluation of the benefit-to-risk ratio of the various anesthetic techniques in individuals. The similar incidence of reactions according to sex before adolescence suggests a role for sex hormones in the increase of anaphylaxis observed in women.

Section snippets

Study design

Data from patients who experienced an immediate hypersensitivity reaction (HSI) during anesthesia suspected of being allergic in origin were prospectively included in the GERAP national register. The mechanism of the reaction (immediate hypersensitivity reaction-IgE-mediated [HSI-IgE] or nonimmunologic or immunologic other than immediate hypersensitivity reaction not mediated by IgE [HSI–non-IgE]) was assessed on the basis of a standardized diagnostic protocol performed in allergo-anesthesia

GERAP database

A total of 2516 patients were included. At the end of the allergy workup, a diagnosis of IgE-mediated immediate hypersensitivity reaction was established in 1816 cases (72.18%), whereas the remaining 700 cases (27.82%) were considered non–IgE-mediated hypersensitivity reactions. The rate of hypersensitivity reactions and the distribution according to the mechanism of hypersensitivity remained stable throughout the entire study period.

The most common causes of anaphylactic reactions were NMBAs

Discussion

This combined analysis of 3 different databases allows us to provide a nationally based estimate of the incidence of immediate IgE-mediated allergic reactions occurring during anesthesia, according to sex, age, and causal substance. To our knowledge, this report represents the first attempt to provide an accurate estimate of the frequency of allergic reactions using the capture-recapture method and the largest cohort of patients available in the literature. It confirms the general view that

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We conducted this meta-analysis to summarize the available evidence and evaluate the relationship between a history of allergies/allergic diseases and perioperative anaphylaxis to offer preventive decision support.
Systematic review and meta-analysis of observational studies.
We searched the MEDLINE (OVID), EMBASE, and the Cochrane Central Register of Controlled Trials databases for observational studies. Two investigators independently performed the search, screened the articles, and collected the study details.
Several databases were systematically searched to evaluate the relationship between a history of allergies/allergic diseases and perioperative anaphylaxis using subgroup analysis, sensitivity analysis and meta-regression.
A total of 19 studies involving 672 anaphylaxis episodes, 5608 immune-mediated reactions, and 1126 severe episodes met the eligibility criteria and were included in this meta-analysis. Drug allergies, food allergies, a history of allergies, and atopy increased the incidence of perioperative anaphylaxis (Drug allergies, odds ratio [OR] 3.54, 95% confidence interval [CI] 1.07–11.69; Food allergies, OR 2.29, 95% CI 1.23–4.26; A history of allergies, OR 4.86, 95% CI 3.65–6.49; Atopy, OR 3.58, 95% CI 1.47–8.71), but not the presence of immune-mediated reactions and the severity of perioperative anaphylaxis.
Patients with previous drug allergies, food allergies, a history of allergies, or atopy are more likely to develop anaphylaxis during the perioperative period. Additional studies should be carried out to determine whether a history of allergies/allergic diseases is a major factor for perioperative anaphylaxis when confounders are controlled.
Paediatric perioperative hypersensitivity: the performance of the current consensus formula and the effect of uneventful anaesthesia on serum tryptase
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Paired sampling of acute (aST) and basal (bST) serum tryptase has been recommended when investigating patients with a suspected perioperative hypersensitivity (POH) reaction. In the current consensus formula, an aST value exceeding (1.2×bST+2) confirms mast cell activation. The current consensus formula has been validated in adults but not in children.
We prospectively included 96 children who underwent uneventful anaesthesia and sampled serum tryptase at baseline and 60–90 min after induction. Tryptase changes were then compared with those in 94 children with suspected POH who were retrospectively included from four reference centres in Belgium, France, and Denmark.
We observed a median decrease in serum tryptase during uneventful anaesthesia of 0.41 μg L⁻¹ (–15.9%; P<0.001). The current consensus formula identified mast cell activation in 31.9% of paediatric POH patients. After generating receiver operating characteristic curves through 100 repeated five-fold cross-validation, aST>bST+0.71 was identified as the optimal cut-off point to identify mast cell activation. This new paediatric formula has higher sensitivity than the current consensus formula (53.2% vs 31.9%, P<0.001) with a specificity of 96.9%. Analysis in the subpopulation where a culprit was identified and in grade 3–4 reactions similarly yielded higher sensitivity for the new paediatric formula when compared with the current consensus formula (85.3% vs 61.8%; P=0.008 and 78.0% vs 48.8%; P<0.001, respectively). Internally cross-validated sensitivity and specificity were 53.3% and 93.3%, respectively.
This is the first study suggesting the need for an adjusted formula in children to identify perioperative mast cell activation as tryptase is significantly lowered during uneventful anaesthesia. We propose a new formula (aST>bST+0.71) which performs significantly better than the current consensus formula in our multicentric paediatric population.
Pholcodine and allergy to neuromuscular blocking agents: where are we and how did we get here?
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Anaphylaxis: A 2023 practice parameter update
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This practice parameter update focuses on 7 areas in which there are new evidence and new recommendations. Diagnostic criteria for anaphylaxis have been revised, and patterns of anaphylaxis are defined. Measurement of serum tryptase is important for diagnosis of anaphylaxis and to identify underlying mast cell disorders. In infants and toddlers, age-specific symptoms may differ from older children and adults, patient age is not correlated with reaction severity, and anaphylaxis is unlikely to be the initial reaction to an allergen on first exposure. Different community settings for anaphylaxis require specific measures for prevention and treatment of anaphylaxis. Optimal prescribing and use of epinephrine autoinjector devices require specific counseling and training of patients and caregivers, including when and how to administer the epinephrine autoinjector and whether and when to call 911. If epinephrine is used promptly, immediate activation of emergency medical services may not be required if the patient experiences a prompt, complete, and durable response. For most medical indications, the risk of stopping or changing beta-blocker or angiotensin-converting enzyme inhibitor medication may exceed the risk of more severe anaphylaxis if the medication is continued, especially in patients with insect sting anaphylaxis. Evaluation for mastocytosis, including a bone marrow biopsy, should be considered for adult patients with severe insect sting anaphylaxis or recurrent idiopathic anaphylaxis. After perioperative anaphylaxis, repeat anesthesia may proceed in the context of shared decision-making and based on the history and results of diagnostic evaluation with skin tests or in vitro tests when available, and supervised challenge when necessary.
Drug-induced hypersensitivity reactions in a Lebanese outpatient population: A decade-long retrospective analysis (2012-2021)
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Drug hypersensitivity reactions (DHRs) are becoming more common as a result of increasing prevalence and case complexity. Allergists and clinical immunologists worldwide are challenged daily to adequately diagnose and manage these reactions. Data in the literature regarding DHR outpatient consultations are scarce worldwide, limited in the Middle East, and currently unavailable in Lebanon.
This retrospective study aimed to evaluate the characteristics of all reported DHRs over 10 years in a tertiary-care allergy clinic in Lebanon.
We conducted a decade-long (2012-21) retrospective analysis of the archived medical records of patients with a history of DHRs. Demographics, clinical history, diagnostic tools, and characteristics of the DHRs were collected and analyzed.
A total of 758 patients experienced DHRs to therapeutic molecules provided for ambulatory care. Our results identified 72 medications. The most frequently implicated drug classes included β-lactam antibiotics (53.8%), followed closely by nonsteroidal anti-inflammatory drugs (48.9%). Of the 758 patients, 32.6% reported DHRs to multiple molecules, and 11.8% reported concomitant DHRs to 1 or several molecules provided in the perioperative setting. Of those, opioids and neuromuscular blocking agents were the 2 most common therapeutic classes. Furthermore, we evaluated the cross-reactivity between molecules of the same class. In neuromuscular blocking agents, rocuronium and cisatracurium were the most commonly cross-reactive, and for opioids, the most common association we recorded was with morphine and pethidine.
Our findings constitute the first step toward a more comprehensive evaluation of the clinical characteristics of DHRs in Lebanon.
Epidemiology of perioperative anaphylaxis in France in 2017–2018: the 11th GERAP survey
2024, British Journal of Anaesthesia
Perioperative anaphylaxis is rare but is associated with significant morbidity. This complication has been well described in France by the GERAP (Groupe d'Etude des Réactions Anaphylactiques Périopératoires), a network focused on its study. The epidemiology of perioperative anaphylaxis is evolving, influenced by environmental factors and clinical practice. The aim of this study was to update the epidemiology of perioperative anaphylaxis in France.
This multicentre retrospective study was performed in 26 allergy clinics of the GERAP network in 2017–8.
There were 765 patients with perioperative anaphylaxis included. Most cases were severe, with 428 (56%) reactions graded as 3 or 4 according to the Ring and Messmer classification. Skin test results were available for 676 patients, with a culprit agent identified in 471 cases (70%). Neuromuscular blocking agents were the main cause of perioperative anaphylaxis (n=281; 60%), followed by antibiotics (n=118; 25%) and patent blue dye (n=11; 2%). Cefazolin was the main antibiotic responsible for perioperative anaphylaxis (52% of antibiotic-related reactions). Suxamethonium and rocuronium were the main neuromuscular blocking agents responsible for perioperative anaphylaxis with 7.1 (6.1–8.4) and 5.6 (4.2–7.4) reactions per 100,000 vials sold, respectively, whereas cefazolin-related cases were estimated at 0.7 (0.5–0.9) reactions per 100,000 vials sold.
Our results confirm that most commonly identified triggering agents remain neuromuscular blocking agents. Reactions to antibiotics, particularly cefazolin, are becoming increasingly frequent. The origin of sensitisation to cefazolin is unknown, as no cross-sensitisation has been described, and it should be the subject of further study. Perioperative anaphylaxis should be followed over the years and understood given the changing triggers.
ClinicalTrials.gov (NCT 04654923).

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: Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest.

^∗: Groupe d’Etudes des Réactions Anaphylactoïdes Peranesthésiques: Angers: C. Cottineau, MD, M. Drouet, MD. Besançon: P. Girardin, MD, P. Koeberlé, MD, M. Vigan, MD. Bordeaux - Pellegrin Tripode: S. Guez, MD, P. Maurette, MD, PhD. Brest: J. C. Rakotoseheno, MD. Caen: D. Laroche, MD, M. C. Vergnaud, MD. Châlons-sur-Saône: P. Scherer, MD. Cherbourg: D. Herbin, MD. Clermont-Ferrand: O. Outtas, MD. Colmar: O. Theissen-Laval, MD. Dieppe: B. Deschamps, MD. Dijon: E. Collet, MD, N. Louvier, MD, S. Seltzer, MD. Dreux: B. Duffin, MD. Epinal: E. Beaudoin, MD. Grasse: P. Dugué, MD. Grenoble: M. Honarmand-Pepin, MD, C. Jacquot, MD. Lille Institut Catholique: C. Castelain-Hacquet, MD. Le Kremlin-Bicêtre: C. Fessenmeyer, MD. Lille CHU: A. Facon, MD. Limoges: I. Orsel, MD, J. Sainte-Laudy, MD. Lorient: C. Bernard, MD. Lyon: Y. Benoît, MD, N. Diot-Junique, MD, J. Dubost, MD, R. Dubost, MD, L. Guilloux, MD, I. Topenot, MD. Marseille: J. Birnbaum, MD, D. Vervloët, MD, PhD. Montpellier: P. Demoly, MD, PhD, M. C. Bonnet-Boyer, MD. Nancy: I. Gastin, MD, J. L. Guéant, MD, PhD, M. C. Laxenaire, MD, PhD, P. M. Mertes, MD, PhD, G. Kanny, MD, PhD, D. A. Moneret-Vautrin, MD, PhD, C. Mouton, MD. Nantes: S. Decagny, MD, M. Pinaud, MD, F. Wessel, MD. Narbonne: C. Gallen, MD. Nice: E. Aguinet, MD, S. Leroy, MD, G. Occelli, MD. Nîmes: M. Joncourt, MD. Orléans: J. P. Delalande, MD, B. Lemaire, MD, W. S. Mfam, MD. Paris Bichat: S. Chollet-Martin, MD, PhD, C. Neukirch, MD, P. Nicaise-Roland, MD, C. Sauvan-Pistof, MD. Paris-Pitié: A. M. Korinek, MD. Paris-Necker: C. Karila, MD. Paris-Pasteur: M. T. Guinnepain, MD. Paris-Créteil: M. Bellanger, MD. Paris-Roosevelt: M. Dona, MD, A. Seringulian, MD. Paris-Saint-Joseph: M. L. Megret-Gabeaud, MD. Paris-Tenon: N. Abuaf, MD, H. Gaouar, MD, J. E. Antegarden, MD, F. Leynadier, MD, PhD. Poitiers: K. Breuil, MD, L. Grandon, MD. Reims: A. Gallet-Browaeys, MD, F. Lavaud, MD, J. M. Malinovsky, MD, PhD. Rennes: Y. Delaval, MD, M. M. Lucas, MD, C. Rochefort-Morel, MD. Rouen: Y. Meunier, MD, D. Provost, MD. Saint-Etienne: C. Dzviga, MD, M. Mangin, MD. Saint-Nazaire: J. P. Mallet, MD. Strasbourg: R. Stenger, MD, S. Le Borgne, MD, J. Valfrey, MD. Tarbes: J. Gayraud, MD. Toulouse-Larrey: A. Didier, MD, PhD, D. Giamarchi, MD. Toulouse-Rangueil: I. Migueres, MD. Tours: P. Carré, MD.

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Food, drug, insect sting allergy, and anaphylaxisAnaphylaxis during anesthesia in France: An 8-year national survey

Background

Objective

Methods

Results

Conclusion

Section snippets

Study design

GERAP database

Discussion

Br J Anaesth

Ann Fr Anesth Reanim

Ann Fr Anesth Reanim

Ann Fr Anesth Reanim

Ann Fr Anesth Reanim

J Allergy Clin Immunol

J Allergy Clin Immunol

Lancet

Ann Fr Anesth Reanim

J Allergy Clin Immunol

Med Clin North Am

Immunol Allergy Clin North Am

Clin Immunol

Hum Immunol

Mol Immunol

Mortality related to anaesthesia in France: analysis of deaths related to airway complications

Anaesthesia

Quality and safety indicators in anesthesia: a systematic review

Anesthesiology

Equipment-related incidents in the operating room: an analysis of occurrence, underlying causes and consequences for the clinical process

Qual Saf Health Care

Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies

JAMA

Adverse drug reactions: back to the future

Br J Clin Pharmacol

Comparing reporting rates of adverse events between drugs with adjustment for year of marketing and secular trends in total reporting

J Biopharm Stat

Rocuronium and anaphylaxis–a statistical challenge

Acta Anaesthesiol Scand

Can spontaneous adverse event reporting systems really be used to compare rates of adverse events between drugs?

Anesth Analg

[Application of the capture/recapture method to spontaneous reporting in drug surveillance]

Thérapie

Using a capture-recapture method to assess the frequency of adverse drug reactions in a French university hospital

Br J Clin Pharmacol

Estimating the rate of adverse drug reactions with capture-recapture analysis

Am J Health Syst Pharm

Food, drug, insect sting allergy, and anaphylaxis
Anaphylaxis during anesthesia in France: An 8-year national survey