Arterial and Venous Thrombotic Complications Following Recreational Nitrous Oxide Misuse: A Comprehensive Review.

Recreational nitrous oxide (N2O) misuse has increased markedly over the past decade, particularly among adolescents and young adults. Although neurological toxicity is well established, venous and arterial thrombotic events remain underrecognized in cardiovascular practice. A comprehensive review of the literature was performed by searching PubMed/MEDLINE, Embase, and Google Scholar from inception to January 2026, using combinations of "nitrous oxide," "thrombosis," "pulmonary embolism," "deep vein thrombosis," "stroke," "myocardial infarction," "aortic thrombus," and "homocysteine." All case reports, case series, observational studies, and systematic reviews published in English or French reporting thrombotic events temporally associated with recreational N2O use were included. Eighteen studies comprising over 40 individual thrombotic events were identified. Manifestations include deep vein thrombosis, pulmonary embolism, cerebral venous sinus thrombosis, ischemic stroke, acute limb ischemia, myocardial infarction, and aortic thrombi. Patients were predominantly young (median age 24-26 years), predominantly male (approximately 70%), and lacked conventional cardiovascular risk factors. Hyperhomocysteinemia was nearly universal, often despite normal serum vitamin B12 levels. N2O irreversibly inactivates vitamin B12-dependent methionine synthase, resulting in functional cobalamin deficiency and a prothrombotic state through endothelial dysfunction, platelet activation, and impaired fibrinolysis. Failure to identify N2O exposure may lead to diagnostic delay and recurrent events. Management requires site-specific anticoagulation or antiplatelet therapy, prompt parenteral vitamin B12 replacement, and cessation of N2O use supported by addiction care. Increased awareness among vascular specialists is essential for timely diagnosis and prevention of recurrence.