Exposure to nitrous oxide may result in acute vitamin B12 deficiency, with megaloblastic anemia and neurologic deficits. While the hematologic changes may be short lived, the neurologic changes may be slow to resolve and can lead to long term morbidity.
Mechanism: Nitrous oxide oxidizes cob(I)alamin, which inactivates methionine synthase.
People at risk:
(1) anesthesiologists, dentists and other professionals chronically exposed to nitrous oxide
(2) persons who chronically abuse nitrous oxide
(3) persons with unsuspected vitamin B12 deficiency (elderly, malabsorption, deficient diet, after prolonged illness) having a long surgical procedure with nitrous oxide as one of the anesthetic agents
Patients receiving methotrexate should avoid nitrous oxide, but the problem involves intracellular folate metabolism rather than cobalamin.
Clinical findings:
(1) unexpected megaloblastic anemia and/or neurologic deficit (demyelination, subacute combined degeneration of the spinal cord, encephalopathy)
(2) onset following surgery or other exposure to nitrous oxide, sometimes after several days or even weeks
Neurologic symptoms may include: numbness, paresthesias, clumsiness, impaired gait, dysarthria, dysequilibrium, sphincter impairment, impotence, muscle weakness, altered reflexes, and impaired thinking.
Laboratory findings:
(1) increased MCV and hypersegmented neutrophils
(2) serum levels of vitamin B12 may be low in a person with nutritional deficiency or within the normal range for a person with chronic exposure
(3) serum levels of folate normal
(4) increased serum and urine methylmalonic acid
(5) increased serum and urine homocysteine
Administration of cobalamin, folinic acid and/or methionine may prevent or treat the syndrome. Some patients who receive cobalamin after severe neurologic deficits have developed may have residual deficits.
