Plasma catecholamine concentrations during a 72-hour aminophylline infusion in children with acute asthma

To explore the possibility that theophylline may act through adrenomedullary secretion of catecholamines, we examined the time courses of plasma norepinephrine (NE), epinephrine (E), and theophylline concentrations and peak expiratory flow (PEF) in nine children with an acute exacerbation of asthma receiving a 72-hour constant infusion of aminophylline. These measurements were made before (baseline) and at 2, 24, 48, and 72 hours after the infusion began. Plasma theophylline concentrations were kept constant in a near midpoint therapeutic range (mean ± SEM, 14.1 ± 1.3 to 16.1 ± 1.1 μg/ml) during the 24- to 72-hour infusion periods. Compared with the respective baseline values (383.8 ± 56.0 and 67.6 ± 11.8 pg/ml for NE and E), the following postinfusion plasma catecholamines reached statistically significant difference: 664.0 ± 125.1 pg/ml for NE at 24 hours ( p < 0.05), and 214.9 ± 57.8, 233.7 ± 82.2, and 137.6 ± 39.4 pg/ml for E at 2, 24, and 48 hours ( p < 0.01). Despite the fact that similar plasma theophylline concentrations were maintained, plasma E, which peaked at 24 hours after dose, returned toward the baseline at the end of infusion (99.7 ± 24.1 pg/ml), whereas this trend was not observed for NE. The postinfusion PEF increased ( p < 0.01) in a stepwise fashion, compared with the baseline, as the infusion progressed. The change in PEF correlated significantly ( p < 0.002) with plasma theophylline concentrations but not with the increase in plasma E from the baseline. Theophylline concentrations did not correlate with the increase in plasma NE or E from the baseline. Our results suggest that theophylline in clinically relevant concentration appears to stimulate transiently adrenomedullary secretion of catecholamines, but its stimulative effect on sympathetic neurons may be relatively well maintained during the aminophylline infusion. However, the clinical implication of our findings remains uncertain and requires further studies.