N2O anesthesia may exacerbate hyperhomocysteinemia and endothelial dysfunction in patients with renal impairment

To the Editor: Patients with renal impairment have elevated homocysteine levels and are at high risk of cardiovascular complications [1]. Herein, we caution against the use of nitrous oxide (N2O) anesthesia for these patients. Under most conditions, N2O appears to be inert, but prolonged exposure to the gas leads to significant increases in plasma homocysteine levels in patients presenting for elective craniotomy [2]. N2O directly inhibits methionine synthase, which contains cobalamin as a prosthetic group and catalyzes a folate-dependent conversion of homocysteine to methionine. Recently, Selzer et al [3] have described the neurologic deterioration and death of a child anesthetized twice with N2O before the diagnosis of 5,10-methylenetetrahydrofolate reductase (MTHFR) deficiency was established. The N2O-induced defect of methionine synthase superimposed on an inherited defect of MTHFR caused the death of the reported patient. The adverse effects of N2O were reported in two other children with severe dietary cobalamin deficiency. One developed acute neurologic deficit six days after N2O anesthesia, and the other showed hypotonia, dehydration, and acidosis three weeks after N2O anesthesia. Acute rise in plasma homocysteine level causes substantial impairment of endothelial function in healthy volunteers [4]. It is likely that when such endothelial dysfunction occurs in patients with renal impairment, it exacerbates the vascular dysfunction. The above-mentioned catastrophic events may provide us a cautionary message; plasma homocysteine and methionine levels should be closely monitored in patients with renal impairment undergoing N2O anesthesia. Pretreatment with vitamins (folic acid, vitamin B6, and B12) may block the N2O-induced increase in homocysteine level in at-risk individuals.