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Dose-response relationship of doxapram in the therapy for refractory idiopathic apnea of prematurity
Insights
Doxapram effectively treats idiopathic apnea of prematurity in infants when aminophylline fails. Starting with a low dose of 0.5 mg/kg/h is recommended for safe and effective neonatal apnea treatment.
Area of Science:
- Neonatal Medicine
- Pharmacology
Background:
- Idiopathic apnea of prematurity is a common challenge in neonates.
- Aminophylline is a standard treatment but can be ineffective in some cases.
Purpose of the Study:
- To evaluate the efficacy and safety of doxapram in infants with apnea of prematurity refractory to aminophylline.
- To determine optimal dosing and serum concentrations for doxapram treatment.
Main Methods:
- Eighteen infants received incremental doses of doxapram (0.5-2.5 mg/kg/h).
- Continuous monitoring of heart rate, thoracic impedance, and transcutaneous PO2 was performed.
- Serum doxapram concentrations were measured at response.
Main Results:
- Doxapram response rates increased with dosage, reaching 89% at 2.5 mg/kg/h.
- Effective serum doxapram concentration was >1.5 micrograms/mL.
- Increased minute ventilation and decreased PCO2 were observed with higher doses.
- Blood pressure elevation occurred at doses >1.5 mg/kg/h.
Conclusions:
- Doxapram is an effective treatment for refractory neonatal apnea.
- A starting dose of 0.5 mg/kg/h is recommended.
- Careful dose titration and monitoring are necessary due to potential side effects like elevated blood pressure.
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 micrograms/mL, and all infants who responded had levels greater than 1.5 micrograms/mL. BP was significantly elevated at doses higher than 1.5 mg/kg/h (P less than .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.