Dose-Response Relationship of Doxapram in the Therapy for Refractory Idiopathic Apnea of Prematurity

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Abstract
Eighteen infants with idiopathic apnea of prematurity refractory to therapeutic levels of aminophylline were treated with incremental doses of doxapram beginning at 0.5 mg/kg/h. Continuous recording of heart rate, thoracic impedance, and transcutaneous Po2 demonstrated that 47% of the infants satisfied objective response criteria at the lowest dose, 53% responded at 1.0 mg/kg/h, 65% at 1.5 mg/kg/h, 82% at 2.0 mg/kg/h, and 89% at the highest allowed dose of 2.5 mg/kg/h. The mean serum doxapram concentration at the response dose was 2.9 ± 1.3 µg/mL, and all infants who responded had levels greater than 1.5 µg/mL. BP was significantly elevated at doses higher than 1.5 mg/kg/h (P < .05). Minute ventilation significantly increased and Pco2 significantly decreased as the doxapram dosage was increased (P = .02). Terminal elimination half-life was 9.9 ± 2.9 hours. When doxapram is used for treatment of refractory neonatal apnea the starting dosage should be no more than 0.5 mg/kg/h.

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