Doxapram Dosing for Apnea of Prematurity Based on Postmenstrual Age and Gender: A Randomized Controlled Trial

• Published in: Paediatric drugs 2016-12, Vol.18 (6), p.443-449
• Main Authors: Greze, E., Benard, M., Hamon, I., Casper, C., Haddad, F. E., Boutroy, M.-J., Hascoët, J.-M.
• Format: Article
• Language: English
• Subjects: Apnea neonatorum; Caffeine; Care and treatment; Continuous positive airway pressure; Diagnosis; Drug therapy; Health aspects; Human health and pathology; Infants (Premature); Internal Medicine; Life Sciences; Medicine; Medicine & Public Health; Original Research Article; Patient outcomes; Pediatrics; Pharmacotherapy
• ISSN: 1174-5878; 1179-2019
• DOI: 10.1007/s40272-016-0192-2

Introduction Doxapram is used as a third-line treatment for apnea unresponsive to caffeine and continuous positive airway pressure (CPAP) in preterm infants. Objectives The objectives of this study were to compare the effects of dosing adjusted for gender and postmenstrual age (PMA) (GrA) versus infants’ weight alone (GrW) on doxapram plasma levels, clinical efficacy, and side effects. Methods This was a randomized, double-blind study, including premature infants for whom optimized caffeine and CPAP therapy for apnea of prematurity had failed. Failure was defined as the persistence of more than one significant apnea per hour over an 8-h period. Plasma levels of doxapram and ketodoxapram were measured with high-performance liquid chromatography (HPLC) 48 h after the onset of treatment. Dosing aimed to maintain the combined doxapram and ketodoxapram plasma level in the therapeutic range of 1.5–4 mg/l. Infants were followed-up for 4 days after the onset of treatment. Results A total of 85 infants were included: 46 in GrW (27.7 ± 1.9 weeks’ gestational age [GA]), 39 in GrA (27.9 ± 1.4 weeks’ GA); available plasma levels showed that 25 of 40 in the GrW group and 27 of 37 in the GrA group had levels within the therapeutic range ( p  = 0.344). Of note, plasma level variance was significantly higher in GrW for doxapram + ketodoxapram (1.87 vs. 0.89; p  = 0.028). Clinical efficacy was better in the GrA group, with a reduction from 32 to 3 of 38 (76 %) infants with significant apnea versus 30 to 5 of 45 (56 %) in the GrW group ( p