PhD defence N. (Naomi) Ketharanathan

Summary:

Severe traumatic brain injury is the one of the leading causes of disability and death worldwide. Children are especially vulnerable because of their major developmental changes. Pain and sleep medication is a cornerstone of supportive therapy to lower raised intracranial pressure. However there is little evidence which medication should be used and choices are left to the treating physician or institution. This is undesirable because there are serious concerns about safe and effective pharmacotherapy. Also, it is unnecessary. There are techniques and methods to develop ‘ evidence-based’ neuropharmacology.

This thesis describes the current international practice of pain and sleep medication in children with severe traumatic brain injury and investigates different methods to improve our understanding of how commonly used drugs work in the brain. This is done with a technique that measures medication concentrations in the brain (cerebral microdialysis). Furthermore, software was developed to predict medication concentrations in different body compartments (e.g. blood and brain) at different time points. 

The ultimate aim of improving medication strategies is to minimize secondary brain injury and improve outcome. Outcome is explored in this thesis by  evaluating end-of-life decisions regarding withdrawal of life sustaining therapies and long-term survivor outcome.
This thesis is the result of international collaborative efforts from preclinical and clinical institutions (Erasmus MC, Rotterdam, The Netherlands; Red Cross War Memorial Children’s Hospital, University of Cape Town, Cape Town, South Africa; Leiden Academic Center for Drug Research, Leiden, The Netherlands, Amsterdam University medical Center, Amsterdam, The Netherlands).