Extrapulmonary effects of nitric oxide inhalation therapy: time to consider new dosing regimes?

Excerpt

Studies with nitric oxide (NO) inhalation suggest transformation of NO in the lung into a more long-lived bioactive NO species that also has distal effects [1, 2]. The exact nature of these species has not been pinpointed, but probable candidates include circulating nitrite anions and/or S-nitrosothiols [3]. When using inhaled NO therapeutically for pulmonary disorders, the dose is typically expressed as the concentration of NO without adjustments for body size. When inhaling 10 ppm NO, the concentration of NO that reaches the lungs with every breath is the same whether it in a mouse, a premature infant or an adult. The minute ventilation in relation to body weight, however, is about three to four times higher in a premature infant compared with an adult, so the resulting accumulation of bioactive NO metabolites in blood is much greater. This greater accumulation suggests that the dose of inhaled NO should be adjusted in relation to body weight, and also calls for some caution when extrapolating results from animal data to humans. A concentration of inhaled NO that is effective in a small animal may therefore not be sufficient in humans. Conversely, a concentration that is effective and safe in adults may cause unwanted toxic effects in premature infants. …