METABOLIC EVIDENCE OF COBALAMIN DEFICIENCY IN BONE-MARROW CELLS HARVESTED FOR TRANSPLANTATION FROM DONORS GIVEN NITROUS-OXIDE

Nitrous oxide inactivates cobalamin, but clinically apparent sequelae ensue in nondeficient individuals only when exposure is prolonged. The gas is widely used in anesthesia, therefore, and is commonly given to donors during harvesting of their bone marrow cells for transplantation. The present study shows that nitrous oxide administered for only 75-120 minutes induced mild but unequivocal DNA synthetic abnormalities attributable to cobalamin deficiency in the harvested marrow cells of 4 out of 5 donors; the deoxyuridine suppression test in these 4 patients showed abnormal results more than 4 standard deviations above the reference mean. Metabolic evidence of cobalamin deficiency in cryopreserved cells diminished only slightly when they were thawed and retested 1 day later, but was no longer detectable in cells thawed and tested on the 3rd day. In contrast, cells harvested under nitrous oxide-free anesthesia in 4 subjects showed no evidence of cobalamin deficiency in the deoxyuridine suppression test. These results demonstrate that even relatively brief exposure to nitrous oxide induces cobalamin deficiency in harvested bone marrow cells, and that the cells remain metabolically impaired for more than 24 hours. Although clinical sequelae are not apparent at this time, the several potential implications of our findings indicate that the use of nitrous oxide in bone marrow transplantation needs to be evaluated further.