Substance use disorder of equimolar oxygen-nitrous oxide mixture in French sickle-cell patients: results of the PHEDRE study
Authors: Gérardin Marie , Rousselet Morgane , Couec Marie-Laure , Masseau Agathe ,   PHEDRE Group, Chantalat Christelle , Driss Françoise , Guitton Corinne , Debbache Karima , Foïs Elena , Galacteros Frédéric , Habibi Anoosha , Léon Anne , Mattioni Sarah , Santin Aline , Alexis-Fardini Scylia , Augusty Edima , Billaud Marie , Divialle-Doumdo Lydia , Etienne-Julan Maryse , Lemonne Nathalie , Petras Marie , Arnaud Cécile , Kamdem Annie , Pondarré Corinne , Passeron Amélie , Rose Christian , Mornand Pierre , Niakaté Assa , Odièvre Marie-Hélène , Dumesnil Cécile , Lahary Agnès , Ngo Stéphanie , Haustant-Andry Line , Ifrim Romana , Loko Gylna , Couec Marie-Laure , Masseau Agathe , Noël Violaine , Pluchart Claire , Amé Shanti , Paillard Catherine , Chamouine Abdourahim , Garou Alain , Andreu Marie-Rita , Brasme Jean-François , Gardembas Martine , Receveur Marie-Catherine , Runel-Belliard Camille , Lejars Odile , Valentin Jean-Baptiste , Armari Corinne , Makowski Caroline , Cougoul Pierre , Besançon Anne , Ghnaya Habib , Giaccobbi Vanina , Grados Aurélie , Jean Estelle , Thuret Isabelle , Barrault-Anstett Marie-Françoise , Condé Mohamed , N’dizeye Suzanne , Holvoet Laurent , Gondran Guillaume , Piguet Christophe , Castex Marie-Pierre , Berceanu Ana , Simon Pauline , Abouchahla Wadih , Lambilliotte Anne , Cannas Giovanna , Gauthier Alexandra , Poutrel Solène , Monpoux Fabrice , Rohrlich Pierre Simon , Barrelet Audrey , Clouzeau Jérôme , Mallard Adeline , Li Thiao Te Valérie , Merlusca Lavinia , Merlin Etienne , Ruivard Marc , Bodet Damien , Johnson Hyacinthe , Minckes Odile , Colomb-Bottollier Elodie , Khalifeh Tackwa , Ramassamy Alain , Nimubona Stanislas , Toutain Fabienne , Boutet Arnaud , Graveleau Julie , Harchaoui Samir , Lalande Muriel , Navarro Robert , Desbrée Aurélie , Guichard Isabelle , Carausu Liana , Eveillard Jean-Richard , Machin Julie , Pierre Marie-Hélène , Cerutti Diane , Elenga Narcisse , Aquizerate Aurélie , Authier Nicolas , Deheul Sylvie , Roussin Anne , Micallef Joelle , Djezzar Samira ,   French Addictovigilance Network (FAN), Authier Nicolas , Boucher Alexandra , Caous Anne-Sylvie , Deheul Sylvie , Daveluy Amélie , Djezzar Samira , Fouilhé Nathalie , Gibaja Valérie , Le Boisselier Reynald , Micallef Joëlle , Pain Stéphanie , Peyrière Hélène , Roussin Anne , Victorri-Vigneau Caroline , Feuillet Fanny , Jolliet Pascale , Grall-Bronnec Marie , Victorri-Vigneau Caroline 
Published: March 2024

Abstract
Background
In many countries, nitrous oxide is used in a gas mixture (EMONO) for short-term analgesia. Cases of addiction, with significant misuse, have been reported in hospitalized patients. Patients suffering from sickle cell disease (SCD) could represent a high-risk population for substance use disorder (SUD) due to their significant pain crisis and repeated use of EMONO. The objective of the PHEDRE study was to assess the prevalence of SUD for EMONO in French SCD patients.

Results
A total of 993 patients were included. Among 339 EMONO consumers, only 38 (11%) had a SUD, with very few criteria, corresponding mainly to a mild SUD due to a use higher than expected (in quantity or duration) and relational tensions with the care teams. Almost all patients (99.7%) were looking for an analgesic effect, but 68% of patients were also looking for other effects. The independent risks factors associated with at least one SUD criterion were: the feeling of effects different from the expected therapeutic effects of EMONO, at least one hospitalization for vaso occlusive crisis in the past 12 months and the presence of a SUD for at least one other analgesic drug.

Conclusions
The use of EMONO was not problematic for the majority of patients. Manifestations of SUD that led to tensions with healthcare teams should alert and lead to an evaluation, to distinguish a true addiction from a pseudoaddiction which may be linked to an insufficient analgesic treatment related to an underestimation of pain in SCD patients.
Trial registration: Clinical Trials, NCT02580565. Registered 16 October 2015, https://clinicaltrials.gov/