High Incidence of Signs of Neuropathy and Self-Reported Substance Use Disorder for Nitrous Oxide in Patients Intoxicated with Nitrous Oxide

Abstract

<b><i>Introduction:</i></b> The number of patients with excessive nitrous oxide (N<sub>2</sub>O) use and neurological disorders has been rising, indicating an addictive potential of N<sub>2</sub>O. We studied the incidence of self-reported substance use disorder (SUD)-related symptoms, signs of neuropathy, and the patterns of use in N<sub>2</sub>O-intoxicated patients. <b><i>Methods:</i></b> The Dutch Poisons Information Center (DPIC) provides information by telephone on the management of intoxications to healthcare professionals. Retrospective data on signs of neuropathy and patterns of use were collected for all N<sub>2</sub>O intoxications reported to the DPIC in 2021 and 2022. Frequent and heavy use were self-reported as “often/frequent/weekly use” and as “use of tanks or >50 balloons/session,” respectively. From this cohort, we included patients with excessive N<sub>2</sub>O use or signs of neuropathy in a prospective observational cohort study. Online surveys were sent 1 week, 1 month, and 3 months after DPIC consultation. The survey included the drug use disorder questionnaire (validated to measure self-reported substance abuse [SA] and substance dependence [SD] based on Diagnostic and Statistical Manual of Mental Disorders [DSM]-IV-TR criteria) and questions on patterns of use and signs of neuropathy. DSM-IV-TR criteria were translated to DSM-V criteria to score for mild, moderate, or severe SUD, with 2–3, 4–5, or ≥6 symptoms, respectively. <b><i>Results:</i></b> We included 101 N<sub>2</sub>O-intoxicated patients in the retrospective study. Of these, 41% showed signs of neuropathy (<i>N</i> = 41), 53% used N<sub>2</sub>O tanks to fill balloons (<i>N</i> = 53), 71% used them frequently (<i>N</i> = 72), and 76% used them heavily (<i>N</i> = 77). We included 75 patients in the prospective study and 10 (13%) completed the first survey. All 10 patients fulfilled the criteria for SA and SD (DSM-IV-TR, median number of questions answered “yes” = 10/12), all used N<sub>2</sub>O tanks to fill balloons, and 90% (<i>N</i> = 9) experienced signs of neuropathy. After 1 and 3 months, 6/7 and 1/1 patients, respectively, continued to fulfill SA and SD criteria. Translating to DSM-V criteria, 1/10 patients fulfilled the criteria for (self-reported) mild SUD, 1/10 patients for moderate SUD, and 8/10 patients for severe SUD, 1 week after consultation. <b><i>Conclusion:</i></b> The high proportion of N<sub>2</sub>O-intoxicated patients reporting frequent and heavy use of N<sub>2</sub>O indicates an addictive potential of N<sub>2</sub>O. Although follow-up rate was low, all patients fulfilled self-reported SA, SD (DSM-IV-TR), and SUD (DSM-V) criteria for N<sub>2</sub>O. Somatic healthcare professionals treating patients with N<sub>2</sub>O intoxications should be aware of possible addictive behavior in patients. The screening, brief intervention, and referral to treatment approach should be considered to treat patients with self-reported SUD symptoms.

Does nitrous oxide addiction exist? An evaluation of the evidence for the presence and prevalence of substance use disorder symptoms in recreational nitrous oxide users

“…Criterion 1: Taking N 2 O in larger amounts or over a longer period than intended A systematic review of case reports of heavy N 2 O use showed that 98% (of 61) of individuals reported using N 2 O in larger amounts or for longer durations than intended [7]. Further evidence for the presence of this symptom is provided by a survey conducted by Nugteren-Van Lonkhuyzen et al [8] as part of a prospective observational cohort study on neuropathy and self-reported SUD in Dutch patients intoxicated with N 2 O. Nine of 10 users reported using N 2 O in larger amounts or for longer durations than intended.…”

“…Two studies specifically investigated the prevalence of unsuccessful efforts to cut down or stop N 2 O use, rendering contradicting results. Although Nugteren-Van Lonkhuyzen et al [8] concluded that 8 of 10 heavy N 2 O users reported having tried to control their use unsuccessfully, Fidalgo et al [7] found that only two of 59 case reports documented evidence for criterion 2.…”

“…Such binges might last multiple hours and are potentially stimulated by the quick offset of the effects of N 2 O, prompting users to keep using to preserve the desired effects. In the only systematic studies on this topic, Fidalgo et al [7] and Nugteren-Van Lonkhuyzen et al [8] both reported substantial time spent on obtaining or using N 2 O in over 90% of cases. Hence, the evidence regarding time spent obtaining N 2 O seems equivocal, but there is sufficient evidence that heavy N 2 O users spend a great deal of their time using Research shows that the use of N 2 O can ameliorate alcohol, tobacco, cannabis [44] and cocaine [45] craving, but research on craving for N 2 O itself is limited, potentially affected by the absence of craving as a SUD symptom in the DSM-IV [7].…”

“…Furthermore, the majority of heavy users use tanks instead of whippits to fill balloons, often holding the tank between their legs [8].…”

“…The rising use of recreational N 2 O use has caused concern because of its negative health effects, including the potential development of addictive behaviors. However, there is little to no consensus regarding the addictive potential of N 2 O and research on the matter is scarce [7][8][9]. In a recent report, the European Monitoring Center for Drugs and Drug Addiction (EMCDDA) highlighted the lack of understanding of the addictive potential of N 2 O and called for better classification and coding systems as well as standardized case definitions to improve diagnosis, treatment, quantification and understanding of the issue [10].…”