Author Of 1 Presentation
ADEQUACY OF CLONIDINE DOSAGE REGIMENS FOR SEDATION IN MECHANICALLY VENTILATED CHILDREN: A PHARMACOKINETIC SIMULATION STUDY
Abstract
Background
Clonidine is in widespread off-label use as a sedative in mechanically ventilated children, despite limited evidence of efficacy. A variety of dosage regimens have been utilised in practice and in previous research studies. A previous observational study included 692 children who received clonidine though did not report opioid sparing effects though improved time at target sedation was reported. One of the reasons attributed to the lack of an opioid-sparing effect is potential underdosing.
Objectives
This study aimed to simulate clonidine pharmacokinetics (PK) to evaluate adequacy of clonidine dosage regimens used in clinical practice and research studies to attain therapeutic plasma levels.
Methods
Using a previously published PK model the projected plasma concentration levels of 692 mechanically ventilated children (demographics taken from a recent study) were generated. Doses from recently published clinical studies were investigated. Adequacy of each regimen to attain therapeutic clonidine plasma concentrations was assessed.
Results
Clonidine intermittent bolus dosage regimens typically of 1-2 µg/kg six to eight hourly did not attain expected therapeutic concentrations of 2 µg/L. Studies using continuous infusions with or without a loading dose attain therapeutic concentrations. Loading doses expedite this.
Conclusion
The variety of dosage regimens used in previous studies of clonidine may have contributed to the lack of efficacy data to support its use. Simulations of clonidine plasma concentrations based on known population pharmacokinetic parameters suggest a loading dose followed by a continuous infusion is required to achieve adequate steady-state concentrations early in treatment. Further pharmacokinetic-pharmacodynamic studies will further aid in the determination of the optimal clonidine dosage regimen.