1. Pholcodine exposure increases the risk of perioperative anaphylaxis to neuromuscular blocking agents: the ALPHO case-control study
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Paul Michel Mertes, Nadine Petitpain, Charles Tacquard, Marion Delpuech, Cédric Baumann, Jean Marc Malinovsky, Dan Longrois, Aurélie Gouel-Cheron, Diane Le Quang, Pascal Demoly, Jean Louis Guéant, Pierre Gillet, Emmanuelle Aguinet, Pol André Apoil, Jean Eric Autegarden, Faiza Bettayeb, Céline Biermann, Maryline Bordes-demolis, Anca Chiriac, Pierre Antoine Darene, Frédéric Deblay, Sabrina Dessard, Charles Dzviga, Hassan El Hanache, Alain Facon, Yannick Fuhrer, Noémie Gest, Marion Gouitaa, Adela Harpan, Cyrille Hoarau, Lisa Le Guillou, Laurence Lepeltier, Claire Mailhol, Delphine Mariotte, Yannick Meunier, Isabelle Migueres, Martine Morisset, Catherine Neukirch, Dalila Nouar, Yann Ollivier, Isabelle Orsel, Omar Outtas, Minaxi Patel, Christelle Pellerin, Isabelle Petit, Anaïs Pipet, Cécile Rochefort-Morel, Claire Schwartz, Sandrine Seltzer, Alice Seringulian, Angèle Soria, Lilia Soufir, Rodolphe Stenger, Céline Tummino, Marion Verdaguer, Les Hôpitaux Universitaires de Strasbourg (HUS), Biologie et Pharmacologie des Plaquettes sanguines : hémostase, thrombose, transfusion (BPP), Université de Strasbourg (UNISTRA)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Nouvel Hôpital Civil de Strasbourg, Centre Régional de PharmacoVigilance de Lorraine (CRPV Lorraine), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Département Méthodologie Promotion Investigation [CHRU Nancy] (MPI), Centre Hospitalier Universitaire de Reims (CHU Reims), Hémostase et Remodelage Vasculaire Post-Ischémie (HERVI - EA 3801), Université de Reims Champagne-Ardenne (URCA), Service d'anesthésie - réanimation chirurgicale [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Université Paris Cité (UPCité), Anticorps en thérapie et pathologie - Antibodies in Therapy and Pathology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre de référence des maladies héréditaires du métabolisme (MaMEA Nancy-Brabois), Service d'Hépato-gastro-entérologie [CHRU Nancy], Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Service de Pharmacologie Clinique et Toxicologie [CHRU Nancy], The ALPHO study NCT02250729 was requested and supported by the European Medicines Agency (EMA). It was funded by a consortium of pharmaceutical companies marketing pholcodine (Zambon, Urgo, Les Laboratoires Pierre Fabre, Boots, Hepatoum, Biocodex, Sanofi, Laboratoires Bouchara Recordati, GlaxoSmithKline, Alliance Pharmaceuticals Ltd, Bells Healthcare, Pinewood, T & R, Ernest Jackson, Vemedia)., and ALPHO Study Group: Emmanuelle Aguinet, Pol André Apoil, Jean Eric Autegarden, Faiza Bettayeb, Céline Biermann, Maryline Bordes-Demolis, Anca Chiriac, Pierre Antoine Darene, Frédéric Deblay, Sabrina Dessard, Charles Dzviga, Hassan El Hanache, Alain Facon, Yannick Fuhrer, Noémie Gest, Marion Gouitaa, Adela Harpan, Cyrille Hoarau, Lisa Le Guillou, Laurence Lepeltier, Claire Mailhol, Delphine Mariotte, Yannick Meunier, Isabelle Migueres, Martine Morisset, Catherine Neukirch, Dalila Nouar, Yann Ollivier, Isabelle Orsel, Omar Outtas, Minaxi Patel, Christelle Pellerin, Isabelle Petit, Anaïs Pipet, Cécile Rochefort-Morel, Claire Schwartz, Sandrine Seltzer, Alice Seringulian, Angèle Soria, Lilia Soufir, Rodolphe Stenger, Céline Tummino, Marion Verdaguer
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Anesthesiology and Pain Medicine ,[SDV]Life Sciences [q-bio] ,anaphylaxis ,anaesthesia ,quaternary ammonium compounds ,neuromuscular blocking agents ,pholcodine - Abstract
International audience; BackgroundNeuromuscular blocking agents (NMBAs) are among the leading cause of perioperative anaphylaxis, and most of these reactions are IgE mediated. Allergic sensitisation induced by environmental exposure to other quaternary ammonium-containing compounds, such as pholcodine, has been suggested. The aim of this study was to assess the relationship between pholcodine exposure and NMBA-related anaphylaxis.MethodsALPHO was a multicentre case-control study, comparing pholcodine exposure within a year before anaesthesia between patients with NMBA-related perioperative anaphylaxis (cases) and control patients with uneventful anaesthesia in France. Each case was matched to two controls by age, sex, type of NMBA, geographic area, and season. Pholcodine exposure was assessed by a self-administered questionnaire and pharmaceutical history retrieved from pharmacy records. The diagnostic values of anti-pholcodine and anti-quaternary ammonium specific IgE (sIgE) were also evaluated.ResultsOverall, 167 cases were matched with 334 controls. NMBA-related anaphylaxis was significantly associated with pholcodine consumption (odds ratio 4.2; 95% confidence interval 2.3–7.0) and occupational exposure to quaternary ammonium compounds (odds ratio 6.1; 95% confidence interval 2.7–13.6), suggesting that apart from pholcodine, other environmental factors can also lead to sensitisation to NMBAs. Pholcodine and quaternary ammonium sIgEs had a high negative predictive value (99.9%) but a very low positive predictive value (
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- 2023
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