Open AccessSemimechanistic models to relate noxious stimulation, movement, and pupillary dilation responses in the presence of opioids
Author(s) -
MarcoAriño Nicolás,
Vide Sergio,
Agustí Mercè,
Chen Andrew,
Jaramillo Sebastián,
IrurzunArana Itziar,
Pacheco Adrià,
Gonzalez Carmen,
Jensen Erik W.,
CapsiMorales Patricia,
Valencia José F.,
Troconiz Iñaki F.,
Gambus Pedro L.,
Larson Merlin D.
Publication year - 2022
Publication title -
cpt: pharmacometrics and systems pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 37
ISSN - 2163-8306
DOI - 10.1002/psp4.12729
Subject(s) - pupillary response , noxious stimulus , pupillary reflex , neuroscience , stimulation , medicine , anesthesia , psychology , nociception , pupil , receptor
Intraoperative targeting of the analgesic effect still lacks an optimal solution. Opioids are currently the main drug used to achieve antinociception, and although underdosing can lead to an increased stress response, overdose can also lead to undesirable adverse effects. To better understand how to achieve the optimal analgesic effect of opioids, we studied the influence of remifentanil on the pupillary reflex dilation (PRD) and its relationship with the reflex movement response to a standardized noxious stimulus. The main objective was to generate population pharmacodynamic models relating remifentanil predicted concentrations to movement and to pupillary dilation during general anesthesia. A total of 78 patients undergoing gynecological surgery under general anesthesia were recruited for the study. PRD and movement response to a tetanic stimulus were measured multiple times before and after surgery. We used nonlinear mixed effects modeling to generate a population pharmacodynamic model to describe both the time profiles of PRD and movement responses to noxious stimulation. Our model demonstrated that movement and PRD are equally depressed by remifentanil. Using the developed model, we changed the intensity of stimulation and simulated remifentanil predicted concentrations maximizing the probability of absence of movement response. An estimated effect site concentration of 2 ng/ml of remifentanil was found to inhibit movement to a tetanic stimulation with a probability of 81%.