Nitrous oxide and vitamin B12 in sickle cell disease: Not a laughing situation

Nitrous oxide (N₂O) is widely used as an anesthetic or an analgesic. N₂O prolonged and recurrent administration is known to affect vitamin B12 metabolism with subsequent clinical consequences. We report herein the case of a 13-year-old girl with sickle cell disease exhibiting severe neurological and biochemical signs of functional vitamin B12 deficiency due to prolonged and repeated exposure to N₂O. This was an incentive to prospectively investigate functional vitamin B12 deficiency in patients affected by sickle cell disease regularly exposed to N₂O. We measured plasma concentrations of vitamin B12, total homocysteine, methionine and methylmalonic acid in 39 patients with sickle cell disease between 2015 and 2016. No patients developed neurological symptoms related to N₂O administration but 19 patients (49%) had biochemical abnormalities suggesting mildly disturbed vitamin B12 metabolism e.g. decreased B12 vitamin, hypomethioninemia, or slightly increased methylmalonic acid or homocysteine. The clinical case highlight the potential severe deleterious effects of N₂O over exposure on B12 vitamin metabolism in particular in patients affected with sickle cell disease. Conversely, when used without excess even repeatedly, there seem to be no overt clinically relevant abnormalities in vitamin B12 metabolism as observed on the cohort of 39 sickle cell disease affected patients.