Perinatal asphyxia: investigating novel neuroprotective agents and optimising current pharmacotherapy

Abstract

This thesis describes research into potential neuroprotective agents in children born with a severe oxygen shortage at birth (perinatal asphyxia). Standard treatment for this condition is therapeutic hypothermia. During this treatment, the body temperature of the neonate is reduced to 33.5 ºC. Although this treatment has a proven beneficial effect on reducing brain damage as a result of perinatal asphyxia, this condition still has a mortality rate of 30% while an additional 15% of the affected neonates survives with severe disalbilities. Therefore, there is a great need for agents that can provide neuroprotection additional to therapeutic hypothermia to further improve the outcome of these neonates. Additionally, this thesis investigates the pharmacokinetics of often used drugs in this population: morphine, phenobarbital, midazolam and lidocaïne. The focus of these studies was to identify the effect of asphyxia and/of treatment with hypothermia on drug clearance in order to optimise the dose of these drugs in this population.