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Anesthesiology. 2012 Jul;117(1):15-21. doi: 10.1097/ALN.0b013e318259a8cc.

Effect of nitrous oxide exposure during surgery on the homocysteine concentrations of children.

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  • 1Physiology and Experimental Medicine Program, The Hospital for Sick Children, Toronto, Ontario, Canada.



Nitrous oxide converts vitamin B12 to its nonmetabolically active form, inhibits methionine synthase, and results in an elevation of plasma total homocysteine (tHcy). The authors investigated the effect of nitrous oxide anesthesia on the plasma tHcy concentrations in children the morning after surgery and whether blood concentrations of folate and vitamins B12 and B6 were associated with any potential increase.


The authors measured plasma tHcy concentrations in 32 children before and 24 h after initial exposure to nitrous oxide (≥ 2 h). Genotype for methylenetetrahydrofolate reductase C677T and blood concentrations of folate, vitamins B12 and B6, and methylmalonic acid were measured before surgery.


The median age of participants was 11 months (3-126 months). The median (first, third quartile) postoperative plasma tHcy concentration was significantly higher than the preoperative concentration (6.4 [4.7, 8.9] vs. 5.1[4.1, 6.4] μM, P < 0.0001), a 25% (2%, 42%) relative increase. Six of 28 (21%) children with normal, age-appropriate, preexposure plasma tHcy concentrations had postoperative plasma tHcy concentrations greater than the cutoff values. The duration of nitrous oxide exposure was associated positively with the rise in plasma tHcy concentration (R2 = 0.696, P = < 0.001).


Exposure to ≥ 2 h nitrous oxide is associated with a small, albeit statistically significant, increase in postoperative plasma tHcy concentrations the morning after surgery in young children. The clinical significance of this increase is unknown.

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  • Notorious oxide. [Anesthesiology. 2012]
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