Agitation-sedation models for critical care: Insights into endogenous agitation reduction and stimulus

Abstract

Background:

Sedation and agitation management are core treatments in the intensive care unit. This study uses pharmacokinetic–pharmacodynamic (PKPD) models to capture the endogenous agitation response. The identification and validation of these models allow for a better understanding of agitation-sedation dynamics and improves the clinical implementation.

Methods:

A cohort of healthy volunteers (N=25) was exposed to a controlled psychological stimulus, with agitation levels quantitatively measured using heart rate-derived metrics. Endogenous agitation reduction (EAR) coefficients were determined from the post-stimulus decay. Using these parameters and a priori information about the experienced stimulus, the model was validated against the measured agitation data.

Results:

The model demonstrated a good fit between measured and modelled agitation. EAR parameters were identified with 45% of the cohort ranging between 0.003–0.004 $s^{-1}$. Using a population value for EAR still resulted in a good fit to measured data. Minimal differences were observed between female and male participants.

Conclusion:

This study provides further development of PKPD models of agitation-sedation dynamics. The identified EAR parameter can be used in future studies and in the clinical application of these models.