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Observational Study
. 2024 Mar 18;19(1):124.
doi: 10.1186/s13023-024-03133-w.

Substance use disorder of equimolar oxygen-nitrous oxide mixture in French sickle-cell patients: results of the PHEDRE study

Marie Gérardin  1 , Morgane Rousselet  1   2   3 , Marie-Laure Couec  4 , Agathe Masseau  5 ; PHEDRE Group; Aurélie Aquizerate  1 , Nicolas Authier  6 , Sylvie Deheul  7 , Anne Roussin  8 , Joelle Micallef  9 , Samira Djezzar  10 ; French Addictovigilance Network (FAN); Fanny Feuillet  3   11 , Pascale Jolliet  1   3 , Marie Grall-Bronnec  2   3 , Caroline Victorri-Vigneau  12   13
Collaborators, Affiliations
Observational Study

Substance use disorder of equimolar oxygen-nitrous oxide mixture in French sickle-cell patients: results of the PHEDRE study

Marie Gérardin et al. Orphanet J Rare Dis. .

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/.

Keywords: Nitrous oxide; Pain; Pseudoaddiction; Sickle cell disease; Substance use disorder.

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Conflict of interest statement

Authors declare that they have no competing interest.

Figures

Fig. 1
Fig. 1
SUD criteria positivity rate. *if there are missing data for some items, the number of patients concerned is mentioned below. DSM SUD criteria: Item 1 = Using more of a substance than planned, or using a substance for a longer interval than desired (missing data for 2 patients). Item 2 = Inability to cut down despite desire to do so (missing data for 2 patients). Item 3 = Spending substantial amount of the day obtaining, using, or recovering from substance use (missing data for 1 patient). Item 4 = Cravings or intense urges to use (missing data for 1 patient). Item 5 = Recurrent substance use may result in a failure to fulfill major role obligations at work, school, or home (missing data for 1 patient). Item 6 = Persistent usage despite persistent or recurrent social or interpersonal problems. Item 7 = Giving up or cutting back on important social, professional, or leisure activities because of use. Item 8 = Using in physically hazardous situations, or usage causing physical or mental harm. Item 9 = Persistent use despite the user's awareness that the substance is causing or at least worsening a physical or mental problem. Item 10 = Tolerance: needing to use increasing amounts of a substance to obtain its desired effects (missing data for 2 patients). Item 11 = Withdrawal: characteristic group of physical effects or symptoms that emerge as amount of substance in the body decreases (missing data for 2 patients) (N=339 patients*)
Fig. 2
Fig. 2
Study population
See this image and copyright information in PMC

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