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The incidence and pathogenesis of acute megaloblastic bone-marrow change and of abnormalities in DNA synthesis, as assessed with the deoxyuridine(dU) suppression test, have been investigated in a prospective study of 70 seriously ill patients admitted to an intensive-care unit. On admission megaloblastic bone-marrow change was present in 22 patients, 18 of whom had been anaesthetised with nitrous oxide for 2-6 h during surgical procedures before admission. 16 of these 18 patients died, compared with 7 of 22 patients in whom haemopoiesis remained normoblastic despite receiving equivalent amounts of nitrous oxide. An abnormal dU-suppression test developed only in patients who had received nitrous oxide; on admission an abnormal dU-suppression test was found in 39 of the 42 patients tested who had been exposed to the anaesthetic. The abnormality produced in the dU-suppression test by nitrous oxide in patients admitted to the intensive-care unit was more severe and recovery was slower than the abnormality seen in patients undergoing cardiac-bypass surgery. During the recovery period from the effects of nitrous oxide the pattern of correction of the dU-suppression test changed from that of vitamin-B12 deficiency to folate deficiency.

In a prospective study the incidence of megaloblastic change after ventilation with nitrous oxide for periods of up to 24 h has been determined and the cause of the altered D.N.A. synthesis studied with the deoxyuridine (dU) suppression test in 22 patients undergoing cardiac bypass surgery. 8 patients who received nitrous oxide and oxygen for 24 h had megaloblastic bone-marrow aspirates and abnormal dU suppression tests at the end of ventilation. 5 patients who received no nitrous oxide had normoblastic aspirates and normal dU suppression test. Of the remaining 9 patients, who received nitrous oxide during the operation only, 3 had abnormal dU suppression tests at 24 h. The abnormality revealed by the dU suppression tests was identical with that found in vitamin-B12 deficiency, but the patients' serum-B12 concentrations were normal. These results suggest that nitrous oxide interferes with the function of vitamin B12. Nitrous oxide oxidises vitamin B12 in vitro, and probably also in vivo when premixed 50% nitrous oxide and 50% oxygen mixture ('Entonox') is given.