(1001) No Laughing Matter: Near-Fatal Thrombosis After Prolonged Recreational Use of Inhaled Nitrous Oxide

Introduction: Recreational nitrous oxide (N20), or "Whippits" is a commonly abused substance. Neurologic toxicities of N20, including demyelination are known, however, a rare side effect is hypercoagulability induced by B12 deficiency, causing hyperhomocysteinemia. We report two cases of ST-elevation myocardial infarction (STEMI), ventricular fibrillation (VF) cardiac arrest and total occlusion of the left anterior descending artery in two young male patients with known long-term N20 abuse.

Description: Case 1 is a 26y male who fell 20' from a tree after using alcohol and N2O, and Case 2 is a 41y male with longstanding N20 abuse. Both men presented to the emergency department, rapidly deteriorated and sustained VF cardiac arrest. Both were diagnosed with STEMI, occurring shortly after N2O inhalation. Emergent cardiac catheterization confirmed 100% occlusion of the left anterior descending artery (LAD) in both cases. Case 1 also had a right coronary artery thrombus. Management consisted of emergent percutaneous coronary angioplasty, stenting of the LAD and ventricular support with an Impella device. Both developed multi-organ failure requiring mechanical ventilation; one progressing to extracorporeal membrane oxygenation. Family members of both patients confirmed chronic recreational N2O abuse. This led to work-up of N2O-induced thrombosis resulting from hyperhomocysteinemia. Through its irreversible oxidation of methyl-cobalamin, chronic N2O use can lead to functional B12 deficiency and elevated methylmalonic acid, resulting in increased homocysteine levels. Both patients had vitamin B12 levels: case 1=1782 pg/mL (on B12 suppl.); case 2=162 pg/mL. Hyperhomocysteinemia was present (29.10 & 27.1 Micromol/L, respectively). Case 2's methylmalonic acid level was 47.89 Micromol/L (100 times upper normal). To date, both men remain in the hospital.

Discussion: Recreational N20 abuse is increasing, despite a new law making it illegal in Michigan as of June, 2024. Regardless, N2O is relatively easy to purchase, often marketed with flavors and mouthpieces designed for abuse. It is extremely important that we, as clinicians, recognize the complications of N2O, perform appropriate testing, and implement a treatment strategy that includes vitamin supplementation and antiplatelet/anticoagulants, as appropriate.