Simulation-Based Gastrointestinal Endoscopy Sedations: A Novel Validation to Multidrug Pharmacodynamic Modeling

Abstract

Pharmacodynamic models have described the interactions between anesthetics. Applying the models to clinical practice is still problematic due to inherent limitations: 1. modeling conditions are different from practice. 2. One model can only describe one endpoint. To tackle these, we propose a new method of model validation for recovery and intraprocedural sedation adequacy with a three-drug pharmacodynamic model using six published clinical studies that contain midazolam, opioid, and propofol. Mean drug dose, intraprocedural sedation level, procedure, and recovery time are extracted from each study. Simulated drug regimens are designed to best approximate study conditions. A published deep sedation model is used for simulation. Model-predicted recovery time and intraprocedural sedation scores are compared with the original clinical study outcomes. The model successfully predicted recovery times in eight out of nine regimens. Lower doses of midazolam are associated with faster recovery. Model prediction of intraprocedural sedation level was compatible with the clinical studies in five out of seven regimens. The three-drug pharmacodynamic model describes the course of gastrointestinal endoscopy sedations from clinical studies well. Model predictions are consistent with the results from clinical studies. The approach implies that large scale validation can be performed repeatedly.