Nitrous oxide abuse leading to extreme homocysteine levels and thrombosis in young adults: a case series

Caris, Martine G; Kuipers, Remko S.; Kiestra, Baruch E; Ruijter, Barry J.; Riezebos, Robert K.; Coppens, Michiel; Mooij, Hans L.

doi:10.1016/j.jtha.2022.10.002

Cited by 14 publications

(7 citation statements)

References 43 publications

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“…Of these, 17 (5%) patients presented with thrombotic events. 4 Myeloneuropathy, including SACD, is already a recognised consequence of recreational nitrous oxide use. 5 6 While there have been occasional reports of an association between nitrous oxide use and VTE, the association is currently under-recognised, despite a plausible mechanism.…”

Section: Discussionmentioning

confidence: 99%

“… 5 6 While there have been occasional reports of an association between nitrous oxide use and VTE, the association is currently under-recognised, despite a plausible mechanism. 4 6 7 These patients frequently seek neurologists’ attention due to toxic myeloneuropathy resulting from functional B12 deficiency. Chronic nitrous oxide misuse leads to reduced vitamin B12 levels and inhibits methionine synthase, resulting in higher homocysteine levels, which in turn may cause thrombotic events.…”

Section: Discussionmentioning

confidence: 99%

“…Chronic nitrous oxide misuse leads to reduced vitamin B12 levels and inhibits methionine synthase, resulting in higher homocysteine levels, which in turn may cause thrombotic events. 4 8 9 Reduced mobility due to nitrous oxide-related myeloneuropathy and quantity of nitrous oxide misuse could also contribute to VTE. As such, VTE prophylaxis may be worth considering, particularly if continued exposure to nitrous oxide is anticipated.…”

Section: Discussionmentioning

confidence: 99%

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Recreational nitrous oxide and thrombotic events: a case series

Patyjewicz,

Mair,

Zaloum

et al. 2024

BMJ Neurol Open

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BackgroundThe study aimed to elucidate the prevalence of nitrous oxide (N2O) usage in patients with unexplained venous thromboembolism (VTE), highlighting the potential association with hyperhomocysteinaemia (HHcy).MethodsWe conducted a retrospective study at the Royal London Hospital, examining cases of N2O-related VTE from March to August 2023. Among 50 patients identified, four (8%) had recent unprovoked VTE. Patient data were collected based on N2O ambulatory emergency care pathway admissions.ResultsAmong the 50 patients identified, four (8%) had recent or concurrent VTE. Three were male (75%), with an ethnic distribution of 50% Asian or Asian British and 50% Black or Black British. Patients were distributed across quintiles of the index of multiple deprivation. All had actual or functional vitamin B12 deficiency.DiscussionThe association between N2O use and VTE requires further investigation, though a plausible mechanism involving HHcy has been proposed. Clinicians should be vigilant for VTE in N2O users, especially those presenting with unexplained symptoms. VTE prophylaxis may be worth considering, particularly if continued exposure to nitrous oxide is anticipated.ConclusionN2O misuse may increase the risk of VTE, warranting attention from healthcare providers. Further research is needed to elucidate this association and inform preventive strategies. Public awareness about the risks of N2O remains essential.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Recreational nitrous oxide and thrombotic events: a case series

Patyjewicz,

Mair,

Zaloum

et al. 2024

BMJ Neurol Open

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“…This prevents the conversion of homocysteine to methionine, leading to hyperhomocysteinemia (Figure 4) [6]. Nitrous oxide abuse has been reported to be associated with thrombotic events, including ischemic stroke, acute coronary syndrome, and venous thromboembolism [9][10][11][12][13][14]. To our knowledge, there are six previous case reports of suspected nitrous oxide-induced cerebral venous thrombosis in which baseline serum homocysteine and cobalamin levels were presented (Table 2), and only two patients had cobalamin deficiency [10,11].…”

Section: Discussionmentioning

confidence: 99%

Nitrous Oxide-Induced Cerebral Venous Thrombosis: A Case Report, Potential Mechanisms, and Literature Review

Banjongjit¹,

Sutamnartpong²,

Mahanupap³

et al. 2023

Cureus

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Cerebral venous thrombosis can result from hypercoagulation, either genetic or acquired. Hyperhomocysteninemia was previously thought to be linked with thrombophilia, although this is still controversial to this present day. In recent years, there has been a notable surge in the recreational use of nitrous oxide, which could potentially lead to hyperhomocysteinemia. We present a case of a 19-year-old female who was diagnosed with cerebral venous thrombosis with intracerebral hemorrhage. She had a history of nitrous oxide abuse, which is known to cause dysfunction of vitamin B12. Additionally, we conducted a literature review of cerebral venous thrombosis following nitrous oxide usage. Investigation showed that her serum vitamin B12 level was <100 pg/mL (reference range 197-771 pg/mL), and homocysteine level was 100.6 µmol/L (reference range 5.0-15.0 µmol/L). After receiving a vitamin B12 supplement, both serum vitamin B12 and homocysteine levels returned to normal. No other risk factors for thrombophilia were detected. Previously reported cases predominantly demonstrated hyperhomocysteinemia. The most likely mechanism of her cerebral venous thrombosis was hyperhomocysteinemia due to vitamin B12 deficiency caused by nitrous oxide abuse. This finding supports the hypothesis that hyperhomocysteinemia can induce cerebral venous thrombosis.

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“…Furthermore, heavy N 2 O use has been associated with mental health problems, including psychotic symptoms and mood disorders [28]. There are also instances of serious thrombotic events following recreational N 2 O use [29] and N 2 O-related deaths, most commonly caused by asphyxiation [15]. Despite the available evidence, 77% of users report to be unaware [30] of the potential harmful effects of N 2 O use.…”

Section: Introductionmentioning

confidence: 99%

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

Back,

Kroon,

Colyer‐Patel

et al. 2023

Addiction

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BackgroundPrevalence of nitrous oxide (N2O) use appears to be increasing in numerous countries worldwide, and excessive use has been associated with physical and mental problems. Because there currently is no consensus whether N2O has addictive potential, we aimed to evaluate the evidence for the presence and prevalence of DSM‐5 substance use disorder (SUD) symptoms in N2O users.AnalysisA literature search was conducted to assess the evidence for the presence of any of the 11 DSM‐5 SUD symptoms in N2O users and the prevalence experiencing those symptoms. A substantial part of the studied N2O users use more than intended (i.e. 46% to 98%) and spend a substantial amount of time using N2O. At least some of the studied N2O users experience interpersonal problems (i.e. 13% to 80%) and use N2O in risky situations, such as driving under the influence. Evidence for the other criteria is either insufficient or inconclusive.ConclusionsThe literature base for the presence and prevalence of DSM‐5 substance use disorder (SUD) symptoms in nitrous oxide (N2O) users is limited and largely consists of qualitative studies and case studies, but it provides consistent evidence for the presence of at least four SUD criteria in heavy N2O users. N2O could well be addictive and should be treated as a potentially addictive substance until systematic assessments can provide evidence‐based guidance to users, healthcare professionals and legislators.

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Nitrous oxide abuse leading to extreme homocysteine levels and thrombosis in young adults: a case series

Cited by 14 publications

References 43 publications

Recreational nitrous oxide and thrombotic events: a case series

Recreational nitrous oxide and thrombotic events: a case series

Nitrous Oxide-Induced Cerebral Venous Thrombosis: A Case Report, Potential Mechanisms, and Literature Review

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

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