Inhaled nitric oxide in premature infants: effect on tracheal aspirate and plasma nitric oxide metabolites

M A Posencheg, A J Gow, W E Truog, R A Ballard, A Cnaan, S G Golombek, P L Ballard, NO CLD Investigators, M A Posencheg, A J Gow, W E Truog, R A Ballard, A Cnaan, S G Golombek, P L Ballard, NO CLD Investigators

Abstract

Objective: Inhaled nitric oxide (iNO) is a potential new therapy for prevention of bronchopulmonary dysplasia and brain injury in premature infants. This study examined dose-related effects of iNO on NO metabolites as evidence of NO delivery.

Study design: A subset of 102 premature infants in the NO CLD trial, receiving 24 days of iNO (20 p.p.m. decreasing to 2 p.p.m.) or placebo, were analyzed. Tracheal aspirate (TA) and plasma samples collected at enrollment and at intervals during study gas were analyzed for NO metabolites.

Result: iNO treatment increased NO metabolites in TA at 20 and 10 p.p.m. (1.7- to 2.3-fold vs control) and in plasma at 20, 10, and 5 p.p.m. (1.6- to 2.3-fold). In post hoc analysis, treated infants with lower metabolite levels at entry had an improved clinical outcome.

Conclusion: iNO causes dose-related increases in NO metabolites in the circulation as well as lung fluid, as evidenced by TA analysis, showing NO delivery to these compartments.

Figures

Figure 1
Figure 1
Box and whisker plot of TA NOx (a) and TA nitrite (b) measurements in iNO-treated infants and control infants by dose of study gas. The box represents 25th and 75th percentile with a median bar. The whiskers represent the 10th and 90th percentiles and the heavy bar represents the mean of the samples. Statistical significance was shown at 20 and 10 p.p.m. between the iNO-treated and control infants for both NOx and nitrite. N=34 and 36 at study entry, 37 and 42 at 20 p.p.m., 30 and 30 at 10 p.p.m., 19 and 23 at 5 p.p.m. for treated and control infants, respectively. Only 11 samples for each group were available at 2 p.p.m. and median NOx values were 32.9 and 28.6 nmol mg–1 protein and nitrite values were 5.7 and 3.7 nmol mg–1 for treated and controls, respectively (not shown).
Figure 2
Figure 2
(a) Box and whisker plot of plasma NOx in iNO-treated and control infants by dose of study gas. NOx concentrations were significantly elevated in treated infants compared with control at 20, 10, and 5 p.p.m. N=48 and 47 at study entry, 46 and 44 at 20 p.p.m., 42 and 45 at 10 p.p.m., 33 and 35 at 5 p.p.m., and 18 and 22 at 2 p.p.m. for treated and control infants, respectively. (b) Plasma NOx concentrations in iNO-treated infants vs control infants by increasing dose of study gas. The median NOx value for treated infants at each dose of iNO as a percent of the median value of the relevant control infants is presented. NOx values did not change with dose of study gas in control infants. N values at each dose of iNO as noted in (a). Error bars represent the proportional 25th and 75th percentile values.

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