title: Pharmacodynamic modelling of drug-induced ventilatory depression and automatic drug dosing in conscious sedation.
abstract: In conscious sedation (CS) procedures, the patient is sedated but retains the ability to breathe spontaneously. Drug-induced ventilatory depression represents a dangerous side effect of CS, possibly leading to hypoventilation and subsequent hypoxia. In this work, we propose a new pharmacodynamic model for drug-induced ventilatory depression. The model presents a parsimonious structure and shows good agreement with experimental data for different drugs. In addition, we explore the innovative idea of regulating drug infusion during CS by means of a feedback control system based on measurements of transcutaneous partial pressure of CO(2). In simulations, the controller proves able to maintain a predefined target of CO(2) despite pain, external disturbances and inter-patient variability in the sensibility to the drug. The implementation of the controller during CS procedures would improve clinical practice minimizing the occurrence of drug-induced ventilatory depression by tailoring drug infusion to patient's needs.
authors.affiliation: Anesthesia Control Group at Automatic Control Laboratory, Swiss Federal Institute of Technology, Zurich, Switzerland. zanderigo@control.ee.ethz.ch
authors.forename: Eleonora
authors.initials: E
authors.lastname: Zanderigo
authors.forename: Antonello
authors.initials: A
authors.lastname: Caruso
authors.forename: Thomas
authors.initials: T
authors.lastname: Bouillon
authors.forename: Martin
authors.initials: M
authors.lastname: Luginbuhl
authors.forename: Manfred
authors.initials: M
authors.lastname: Morari
mesh_terms: D001331:Automation; D002245:Carbon Dioxide / Q000378:metabolism; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003198:Computer Simulation; D016292:Procedural Sedation / Q000379:methods*; D016503:Drug Delivery Systems; D004867:Equipment Design; D005246:Feedback; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage* / Q000494:pharmacology*; D000860:Hypoxia; D007262:Infusions, Intravenous; D010100:Oxygen / Q000378:metabolism; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D012119:Respiration / Q000187:drug effects*
chemical_list: D006993:Hypnotics and Sedatives; D002245:Carbon Dioxide; D010100:Oxygen