lancet-header

Preprints with The Lancet is part of SSRN´s First Look, a place where journals identify content of interest prior to publication. Authors have opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early stage research papers that have not been peer-reviewed. The findings should not be used for clinical or public health decision making and should not be presented to a lay audience without highlighting that they are preliminary and have not been peer-reviewed. For more information on this collaboration, see the comments published in The Lancet about the trial period, and our decision to make this a permanent offering, or visit The Lancet´s FAQ page, and for any feedback please contact preprints@lancet.com.

Pholcodine Consumption Increases the Risk of Perioperative Anaphylaxis to Neuromuscular Blocking Agents: The ALPHO Case-Control Study

26 Pages Posted: 13 Dec 2022

See all articles by Paul-Michel Mertes

Paul-Michel Mertes

Les Hôpitaux Universitaires de Strasbourg - Service d'anesthésie-réanimation chirurgicale

Nadine Petitpain

National Centre of Pharmacovigilance

Charles Tacquard

University of Strasbourg - Department of Anesthesiology

Marion Delpuech

Centre Hospitalier Régional Universitaire de Nancy - MPI Department

Cédric Baumann

Centre Hospitalier Régional Universitaire de Nancy - MPI Department

Jean-Marc Malinovsky

CHU de Reims - Anesthesia and Intensive Care Departmen

Dan Longrois

Université de Rennes 1 - Department of Anesthesiology Critical Care Medicine and Perioperative Medicine

Aurélie Gouel-Cheron

Université Paris Cité - Anesthesiology and Critical Care Medicine Department

Diane Le Quang

Lyon Sud Hospital - Allergology-Anesthesia Department

Pascal Demoly

University of Montpellier - Division of Allergy

Jean-Louis Gueant

University of Lorraine - Nutrition, Genetics, and Environmental Risk Exposure (NGERE); University of Lorraine - Department of Molecular Medicine and Personalized Therapeutics; University of Lorraine - Reference Centre for Inborn Errors of Metabolism (ORPHA67872)

Pierre Gillet

affiliation not provided to SSRN

More...

Abstract

Background: Neuromuscular blocking agents (NMBAs) are the leading cause of perioperative anaphylaxis (POA), most reactions being IgE mediated. Because many subjects with NMBA-related POA have no previous exposure, allergic sensitization 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 POA.

Methods: ALPHO is a multicentre case-control study, commissioned by the European Medicines Agency, comparing pholcodine exposure within a year before anaesthesia between patients with NMBA-related POA (cases) and control patients with uneventful anaesthesia. 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 their pharmacy records. The diagnostic values of anti-pholcodine and anti-quaternary ammonium specific IgE (sIgE) were also evaluated.

Findings: Overall, 167 cases were matched with 334 controls. NMBA-related POA was significantly associated with pholcodine consumption (OR =4·2; CI95% 2·3-7·0), occupational exposure to quaternary ammoniums (OR = 6·1; CI95% 2·7-13·6) and hepato-gastro-intestinal history (OR = 2·1; CI95% 1·3-3·3). Anti-pholcodine and anti-quaternary ammonium sIgEs had a high negative predictive value (99·9%) but a very low positive predictive value (< 3%) for identifying NMBA-related POA.

Interpretation: Patients exposed to pholcodine 12 months prior to NMBA exposure have a significantly higher risk of a NMBA-related POA. These results should encourage a careful re-evaluation of the benefit/risk ratio of pholcodine-containing preparations. The low positive predictive values of pholcodine and quaternary ammonium sIgEs precludes their use to identify a population with a high risk of NMBA-related POA. The strong association of NMBA-related POA with occupational exposure suggests that other environmental factors may also lead to sensitization to NMBAs.

Trial Registration Details: The study protocol is available on ClinicalTrials.gov, NCT02250729.

Funding Information: The ALPHO study (NCT02250729) was funded by a consortium of pharmaceutical companies: Zambon, Urgo, Pierre Fabre, Boots, Hepatoum, Biocodex, Sanofi, LBR, GSK, APL, Bells Healthcare, Pinewood, T & R, Ernest Jackson.

Declaration of Interests: We declare no competing interests.

Ethics Approval Statement: The COMITE de PROTECTION des PERSONNES EsT-111
Hopital de Brabois. Rue du Morvan - 54511 VANDCEUVRE-LES-NANCY Cedex has approved this study.

Keywords: Anaphylaxis, Anaesthesia, Neuromuscular Blocking Agents, Pholcodine, Quaternary ammonium compounds

Suggested Citation

Mertes, Paul-Michel and Petitpain, Nadine and Tacquard, Charles and Delpuech, Marion and Baumann, Cédric and Malinovsky, Jean-Marc and Longrois, Dan and Gouel-Cheron, Aurélie and Le Quang, Diane and Demoly, Pascal and Gueant, Jean-Louis and Gillet, Pierre, Pholcodine Consumption Increases the Risk of Perioperative Anaphylaxis to Neuromuscular Blocking Agents: The ALPHO Case-Control Study. Available at SSRN: https://ssrn.com/abstract=4287475 or http://dx.doi.org/10.2139/ssrn.4287475

Paul-Michel Mertes (Contact Author)

Les Hôpitaux Universitaires de Strasbourg - Service d'anesthésie-réanimation chirurgicale ( email )

Nadine Petitpain

National Centre of Pharmacovigilance

Charles Tacquard

University of Strasbourg - Department of Anesthesiology ( email )

Marion Delpuech

Centre Hospitalier Régional Universitaire de Nancy - MPI Department ( email )

Cédric Baumann

Centre Hospitalier Régional Universitaire de Nancy - MPI Department ( email )

Jean-Marc Malinovsky

CHU de Reims - Anesthesia and Intensive Care Departmen ( email )

Dan Longrois

Université de Rennes 1 - Department of Anesthesiology Critical Care Medicine and Perioperative Medicine ( email )

Aurélie Gouel-Cheron

Université Paris Cité - Anesthesiology and Critical Care Medicine Department ( email )

Diane Le Quang

Lyon Sud Hospital - Allergology-Anesthesia Department ( email )

Pascal Demoly

University of Montpellier - Division of Allergy ( email )

Jean-Louis Gueant

University of Lorraine - Nutrition, Genetics, and Environmental Risk Exposure (NGERE) ( email )

Nancy
France

University of Lorraine - Department of Molecular Medicine and Personalized Therapeutics ( email )

Nancy, F-54000
France

University of Lorraine - Reference Centre for Inborn Errors of Metabolism (ORPHA67872) ( email )

Nancy, F-54000
France

Pierre Gillet

affiliation not provided to SSRN ( email )

No Address Available

Click here to go to TheLancet.com

Paper statistics

Downloads
89
Abstract Views
312
PlumX Metrics