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

Background: Neurologic complications from recreational use of nitrous oxide (N₂O), which are attributed to vitamin B12 deficiency, have been well documented. With increasing dosages and frequency of N₂O use, an additional association with thromboembolisms is becoming apparent. Objectives: To assess thrombotic complications of recreational N₂O use. Methods: All medical charts at the largest hospital in Amsterdam were searched for N₂O use and subsequent neurologic and/or thrombotic events. For patients with thrombotic events, we extracted data on the risk factors for arterial and venous thrombosis as well as serum vitamin B12 and homocysteine concentrations. Results: Between January 2015 and May 2021, 326 patients who reported recreational use of N₂O were identified; of these, 17 (5%) patients presented with severe thrombotic events associated with N₂O (71% men; median age, 26 years [range, 18-53 years]), 5 patients presented with arterial thrombosis (3 with acute coronary syndrome, 1 with femoral artery thrombosis, and 1 with middle cerebral artery thrombus), and 12 patients presented with venous thromboembolisms (10 with pulmonary embolisms, 1 with portal vein thrombosis and 1 with cerebral vein thrombosis). Additionally, homocysteine were concentrations severely increased (median, 125 μmol/L [range, 22-253 μmol/L]; reference, <15 μmol/L). Patients reported use of 400 to 6000 g (ie, 50-750 balloons) of N₂O in 1 day. Fifty percent of these patients had experienced neurologic symptoms before the thrombotic event. Conclusion: We describe an alarming incidence of serious thrombotic events among young adults after excessive recreational use of N₂O, accompanied by extremely high homocysteine concentrations. The upward trend in the recreational use of N₂O warrants more awareness of its dangers among both users and medical professionals. Furthermore, these findings could reopen the discussion on possible associations between hyperhomocysteinemia and thrombosis mediated through N₂O.