Comparison of the effects of acetazolamide and aminophylline on apnea incidence and on ventilatory response to CO2, in preterm infants

Acetazolamide (ACTZ) reduces sleep apnea in adults exposed to high altitude and augments the ventilatory response to CO₂. In order to determine the effect of ACTZ on the ventilatory response to CO₂ and the incidence of apnea in preterm infants, 7 infants (BW, 1070 ± 191 g; postnatal age, 9 ± 7 days) were randomized to receive ACTZ (5 mg/kg/dose 06h for 36 hr) and 7 infants (BW, 1092 ± 292 g; post-natal age, 5 ± 2 days) received aminophylline (AMINO; 8 mg/kg bolus then 2.5 mg/kg Q12h for 36 hr). Minute ventilation (V_E), end-tidal CO₂, (P), ventilatory response to CO₂ number of apneic episodes (≥15 sec duration), and arterial blood gases were measured before and 24–36 hr after starting therapy. In the AMINO group there was a significant decrease in apnea frequency from 6 ± 1 to 2 ± 2 episodes over an 8 hr epoch (P < 0.05), while no significant change was observed in the ACTZ group. The end-tidal CO₂, decreased significantly from 44 ± 7 to 38 ± 6 mmHg in the AMINO group and from 47 ± 5 to 36 ± 5 mmHg in the ACTZ (P < 0.05), which lead to a shift to the left of the CO₂,-response curve in both groups. The slope of the CO₂, response curve did not change Significantly in the AMINO group and decreased in the ACTZ group. There was a significant decrease of pH from 7.43 to 7.26 in the ACTZ group, whereas in the AMINO group pH increased from 7.38 to 7.44. No significant changes in V_E, tidal volume, respiratory rate, lung compliance, or resistance were observed with treatment in any of the two groups. These findings demonstrate that both AMINO and ACTZ decreased end-tidal CO₂ and caused a shift of the CO₂ response curve to the left. Despite these similar effects, ACTZ did not have an effect on apnea incidence. Pediatr Pulmonol. 1994; 17:291–295. © 1994 Wiley-Liss, Inc.