This thesis examines the effect of developmental care in a tertiary NICU in 2 locations in the Netherlands on preterm infants born < 32 weeks gestational age. Following a pilot study with 22... Show moreThis thesis examines the effect of developmental care in a tertiary NICU in 2 locations in the Netherlands on preterm infants born < 32 weeks gestational age. Following a pilot study with 22 preterm infants and their parents, two consecutive randomized controlled trials (n=179, n=164) in which first basic developmental care (use of incubator covers and positioning aids), and then the comprehensive Newborn Individualized Developmental Care and Assessment Program (NIDCAP), an individual approach in which caregiving is based on the behavior of the infant, was studied in preterm infants born < 32 weeks GA. Basic developmental care had no effect on short-term physical and neurological outcomes; a positive effect on psychomotor development at 1 CA, but no effect on neurological and mental development or growth at 1 and 2 years. NIDCAP showed no effect on short-term physical and neurological outcomes as well as no effect on growth, neurological, mental and psychomotor development at 1 and 2 years CA in infants born < 32 weeks, as compared to basic developmental care. Future research should include not only the effect of developmental care in the neonatal centers but also the effect of continuing the intervention once infants are transferred to regional hospitals. Show less
The overall goal was to develop individualized dosing guidelines for the sedatives propofol and midazolam in infants and in critically ill patients, on the basis of population pharmacokinetic... Show moreThe overall goal was to develop individualized dosing guidelines for the sedatives propofol and midazolam in infants and in critically ill patients, on the basis of population pharmacokinetic-pharmacodynamic (PK-PD) modeling. Both under- and oversedation significantly and adversely affects patient outcome. Due to the high intra- and interindividual variability in dose requirements dosing is complicated. In this thesis the interindividual variability in response has been examined by covariate analysis. In this analysis the effects of bodyweight, cardiac function, severity of illness and liver blood flow and the unexplained interindividual variability have been characterized. It was shown that infants require higher doses of propofol because of differences in pharmacokinetics rather than pharmacodynamics. When comparing the results of the PK-PD model of propofol and midazolam in infants, propofol is preferred over midazolam because of the lower interindividual variability in pharmacodynamics compared to midazolam. In critically ill patients severity of the illness was found to be a major determinant of the level of sedation, with lower propofol dosing requirements with increasing severity of illness. The PK-PD models can be used as a basis for individualized dosing of propofol and midazolam, which is essential for optimizing the quality of sedation in clinical practice and will improve patients__ outcome. Show less
