ABSTRACT
The pharmacokinetics (PK) of amoxicillin in asphyxiated newborns undergoing moderate hypothermia were quantified using prospective data (N = 125). The population PK was described by a 2-compartment model with a priori birthweight (BW) based allometric scaling. Significant correlations were observed between clearance (Cl) and postnatal age (PNA), gestational age (GA), body temperature (TEMP), and urine output (UO). For a typical patient with GA 40 weeks, BW 3,000 g, 2 days PNA (i.e., TEMP 33.5°C), and normal UO, Cl was 0.26 L/h (interindividual variability (IIV) 41.9%) and volume of distribution of the central compartment was 0.34 L/kg (IIV of 114.6%). For this patient, Cl increased to 0.41 L/h at PNA 5 days and TEMP 37.0°C. The respective contributions of both covariates were 23% and 27%. Based on Monte Carlo simulations we recommend 50 and 75 mg/kg/24h amoxicillin in three doses for patients with GA 36-37 and 38-42 weeks, respectively.
Subject(s)
Amoxicillin/pharmacokinetics , Anti-Bacterial Agents/pharmacokinetics , Hypothermia/metabolism , Aging/metabolism , Algorithms , Amoxicillin/administration & dosage , Anti-Bacterial Agents/administration & dosage , Birth Weight , Body Temperature , Cohort Studies , Computer Simulation , Female , Gestational Age , Humans , Infant, Newborn , Male , Monte Carlo Method , Prospective Studies , UrodynamicsABSTRACT
AIM: To determine the prevalence and independent relationship between hearing loss and risk factors in a representative neonatal intensive care unit (NICU) population. METHODS: Automated auditory brainstem response (AABR) hearing screening has been introduced since 1998 in the Dutch NICUs. After a second AABR failure, diagnostic ABR was used to establish diagnosis of hearing loss. Newborns who died before the age of 3 months were excluded. In the present study only the NICU infants who were born with a gestational age <30 weeks and/or a birth weight <1000 g between October 1, 1998 and January 1, 2002 were included. Risk factors included in the study were familial hearing loss, in utero infections, craniofacial anomalies, birth weight <1500 g, hyperbilirubinemia, ototoxic medications, cerebral complications, severe birth asphyxia, assisted ventilation > or =5 days and syndromes. RESULTS: A nationwide cohort of 2186 newborns were included. Mean gestational age was 28.5 weeks (SD 1.6) and mean birth weight was 1039 g (SD 256). Prevalence of uni- or bilateral hearing loss was 3.2% (71/2186; 95% CI 2.6-4.1). Multivariate analysis revealed that the only independent risk factors for hearing loss were severe birth asphyxia (OR 1.7; 95% CI 1.0-2.7) and assisted ventilation > or =5 days (OR 3.6; 95% CI 2.1-6.0). CONCLUSION: The prevalence of hearing loss in a representative NICU population was 3.2%. Independent risk factors for hearing loss were severe birth asphyxia and assisted ventilation > or =5 days.
