Speaker: Karel Allegaert

Pharmacotherapy is a powerful tool to improve outcomes in neonates. Clinical pharmacology aims to estimate drug-specific (side)-effects based on pharmacokinetics (PK) and pharmacodynamics (PD). PK (absorption, distribution, metabolism, excretion, ADME) describes the drug concentration over time in a given compartment, like plasma, subcutaneous tissue, or cerebrospinal fluid. PD describes the link between drug concentrations and (side)-effects over time. For analgesics, this can be illustrated by concentration-time profiles in plasma- or cerebrospinal fluid for PK, while PD covers both effects (analgesia) and side effects (sedation, bladder retention, obstipation). Clinical pharmacology also aims to predict and explain variability, a key characteristic of children. The dynamic changes related to maturation and growth in newborns result in a unique setting with extensive variability. Non-maturational changes (like disease, drug-drug interactions, and pharmacogenetics) add to this variability.
Consequently, neonates are a particularly vulnerable subgroup. Analgesics selected, and their dosing regimens should take into account the severity and type of pain, the therapeutic window of the drug, but also the age or developmental state. Translation to safe and effective pharmacotherapy of pain in neonates or infants necessitates a thorough understanding of these clinical pharmacology principles.
These PK-related differences are reflected in age- or weight-dependent changes in dosing, and this will be illustrated for commonly used analgesics. Specific points of interest are differences in metabolism (other metabolites = other safety/efficacy profile), the relevance of a loading dose to ensure effective analgesia, the strengths of multimodal analgesia, and the emerging techniques on loco-regional analgesia. Despite the increasing knowledge, gaps, and questions still remain in the field of neonatal pain. These relate to assessment, prevention, and treatment, as well as long-term outcomes.



Learning Objectives:
1. Upon completion, participants will be able to better use observations on pharmacokinetics and -dynamics in neonates in their clinical practice.
2. Upon completion, participants will be able to better select analgesics and its dosing; this includes aspects related to loading doses and multimodal analgesia in neonates
3. Upon completion, participants will be able to integrate the practice of selection of analgesics with aspects on the safety/efficacy balance.