Drug Therapy in Critically Ill Children

Although widely prescribed, the safety and efficacy of drugs administered to critically ill children is hardly studied in this population. In addition to the age-related maturation of drug-metabolizing enzymes and renal function, acute illness and its treatment modalities may also impact drug disposition and response. More evidence based dosing regimens can be derived only if the effect of factors such as inflammation and disease state on pharmacokinetics as well as pharmacodynamics is known.

The aims of this thesis were:
1. To study the influence of critical illness (inflammation and disease state) in children on midazolam pharmacokinetics, as a surrogate measure of CYP3A activity.
2. To study the safety and efficacy of daily sedation interruption in critically ill children.