Nitric oxide: Toxicity

Nitric Oxide is a colorless, odorless gas that is relatively insoluble in water and is found in naturally atmosphere at concentration range of 10-500 ppb. The concentration has been reported as high as 1500ppb or (1.5ppm) in areas of high traffic or lightning.

NO is potent dilator of the pulmonary circulation and has been used clinically to reduce pulmonary artery pressures. Toxicity results most commonly from:

1. The formation of NO₂ is the result of spontaneous oxidation in the lungs. NO can also spontaneously convert to N₂O₄, but the NO₂ is particularly bad because when combined with water (present naturally in the lungs) it forms nitric acid, which is a potent irritant and can cause pulmonary edema leading to death. The lowest reported dose of NO₂ required to cause problems is 1.5ppm NO₂. The higher the concentration of NO, the higher it is of NO₂ and therefore the more acid is present.
2. The formation of methemoglobinemia is clinically more important in neonates than it is in adults. NO combines with Hemoglobin to produce nitrosyl-hemoglobin, which is then rapidly oxidized to methemoglobin. In a normal RBC with normal enzyme levels, this can be reduced by the enzyme Methemoglobin reductase but neonates have a lower level of this enzyme. Cyanosis appears at levels of 15-20%. Hypoxia will occur when because MetHgb levels get above 30%.

A safe dose of NO appears to be between 1.25 and 80ppm inhaled. At these doses neither significant NO₂ nor methemoglobinemia occurred.

Note that impact of nitric oxide on cGMP is NOT associated with toxicity.