Correspondence
Nitrous Oxide and 5,10-Methylenetetrahydrofolate Reductase
N Engl J Med 2003; 349:1479-1480October 9, 2003
- Article
To the Editor:
Regarding the article by Selzer et al. on the adverse effect of nitrous oxide (July 3 issue),1 I would like to point out that, in 1978, my colleagues and I showed that nitrous oxide inactivated vitamin B12 in vivo.2 My colleague John Amess, as a member of the department of the late David Mollin, observed megaloblastic erythropoiesis in a patient who had received nitrous oxide in 1975 after being injured in a train accident at Moorgate Station on the edge of the City of London. We then conducted a prospective trial in which we showed, using the deoxyuridine suppression test, that nitrous oxide inactivated vitamin B12 in vivo. We provided references to earlier work that had shown this in vitro.
2 ReferencesJohn F. Burman, M.D.
Royal Brompton Hospital, London SW3 6NP, United Kingdom
j.burman@rbh. nthames. nhs. uk 1
Selzer RR ,Rosenblatt DS ,Laxova R ,Hogan K . Adverse effect of nitrous oxide in a child with 5,10-methylenetetrahydrofolate reductase deficiency. N Engl J Med 2003;349:45-50
Full Text | Web of Science | Medline2
Amess JA ,Burman JF ,Rees GM ,Nancekievill DG ,Mollin DL . Megaloblastic haemopoiesis in patients receiving nitrous oxide. Lancet 1978;12:339-342
CrossRef
To the Editor:
The Perspective article by Erbe and Salis (July 3 issue)1 has the potential to cause major changes in the preoperative assessment and intraoperative treatment of huge numbers of people undergoing anesthesia, yet the basis for all this change is one unfortunate case — one case after over 100 years of use of nitrous oxide. It is unrealistic for everyone who receives general anesthetic to have his or her homocysteine levels screened. As much as one would like to know the homocysteine level for the assessment of the risk of atherogenesis, no one is about to require every person, even in youth, to undergo testing. The case reported is worthy, because it teaches us about genetics and new biochemistry. But the case is not a reason to alter the landscape of management in the operating room.
1 ReferencesJeffrey L. Kaufman, M.D.
Vascular Services of Western New England, Springfield, MA 011071
Erbe RW ,Salis RJ . Severe methylenetetrahydrofolate reductase deficiency, methionine synthase, and nitrous oxide -- a cautionary tale. N Engl J Med 2003;349:5-6
Full Text | Web of Science | Medline
Author/Editor Response
I thank Dr. Burman for calling attention to his work with Amess et al. in delineating the mechanism of nitrous oxide–induced megaloblastic erythropoiesis in vivo. In keeping with the absence of megaloblastic changes in patients with 5,10-methylenetetrahydrofolate reductase deficiency,1 the hemoglobin level (11.3 g per deciliter) and the erythrocyte morphology were normal before and after exposure to nitrous oxide in the three-month-old subject of our report. Although unexplained megaloblastic changes serve to warn of potential complications of nitrous oxide use, normal red-cell indexes offer little comfort to caregivers in this regard.
1 ReferencesKirk Hogan, M.D., J.D.
University of Wisconsin Medical School, Madison, WI 53792
khogan@facstaff.wisc. edu Author/Editor Response
The article to which the Perspective article relates was published by the Journal after extensive consideration of the concern to which Dr. Kaufman refers. From the first word in the title and at several important points within the article, the authors specify very clearly the exceptional attributes of this single patient that led to the unfortunate outcome after exposure to a very common anesthetic agent. The further development of powerful DNA methods in recent years made it possible to understand the cause of death in this patient and thereby to shed further light on important, incompletely understood pathophysiological mechanisms.
Geneticists sometimes say, “Treasure your exceptions,” referring to the opportunities we encounter among patients for furthering our understanding of important normal and abnormal human functions. This patient was assuredly an exception — indeed, a very rare one. Careful reading of the report and the Perspective article should allow readers to interpret correctly the relevance of this case report to the neurochemical functions of methionine, rather than making an inappropriate generalization about the risks posed by nitrous oxide, an anesthetic agent with a long and very positive record of safety.
Richard W. Erbe, M.D.
University at Buffalo, Buffalo, NY 14209
