Evidence-Based Pharmacotherapy in Preterm Infants : Aiming at a moving target

Premature born infants require intensive care with many drugs. For most drugs knowledge is lacking on the correct dosage, the effects and the side-effects. This leads to large differences in prescribed drugs for treatment of premature born infants, found by comparing four Dutch hospitals as part of this dissertation. This could be improved through more consensus between hospitals on the optimal treatment, and through extensive research into optimal dosage regimens for preterm born infants.

ZonMw has granted this research to close the knowledge gap with four Dutch hospitals; Máxima MC - Veldhoven, Radboudumc - Nijmegen, MaastrichtUMC - Maastricht, ErasmusMC – Rotterdam. This enabled to study 9 frequently prescribed drugs in preterm born infants; paracetamol, fentanyl, phenobarbital, doxapram, ibuprofen, midazolam, fluconazole, sildenafil and levetiracetam. The first five have been described in this dissertation. The drug amounts could be measured in a very small blood volume, and the effects were studied with appropriate instruments for these patients.

Premature born infants showed to eliminate paracetamol, fentanyl, phenobarbital, doxapram and ibuprofen slower at lower gestational age than at higher gestational age. After birth, the elimination of drugs increased with age. This means that it is no longer appropriate to prescribe one dose per kilogram bodyweight for all premature born infants, but dosage regimens should take gestational age into account, as well as bodyweight, and age after birth. Consequently, the smallest premature born infants may have been overtreated with drugs. This study defined improved dosage regimens of the studied drugs for treatment of premature born infants. Furthermore, good tools for effect measurement in premature born infants have been used successfully, despite the fact that the measurement of effects and side-effects is very complicated in these patients.