The clinical pharmacology of short acting analgo-sedatives in neonates

Effective pain management remains an important indicator of the quality of care provided to neonates, not only from an ethical, but also from a clinical outcome perspective. Significant progresses in non-pharmacological therapies have been made. However - in the meanwhile - neonatal practice also evolved. These shifts in clinical care also induced in a shift in pharmacodynamic end points, and consequently, new pharmacological observations are needed with emphasis on short acting procedural analgo-sedatives. Analgo-sedation in neonates remains a balanced decision based on systematic assessment (pharmacodynamics, PD), followed by titrated administration of the most appropriate analgesic(s) (PK) with subsequent re-assessment (PD) to adapt and further titrate exposure and effects. In this review, we will focus on aspects of the clinical pharmacology (pharmacokinetics (PK) and -dynamics) of newly emerging, short acting analgo-sedatives (midazolam, propofol, remifentanil, inhalational agents, ketamine) in neonates. Based on the currently available information on predictability of disposition and the limited pharmacodynamic side effects (hemodynamics, neuro-apoptosis), it seems that remifentanil is the most promising compound for further evaluation.