title: Computer simulation of intracranial pressure changes during induction of anesthesia: comparison of thiopental, propofol, and etomidate.
abstract: We have developed a computer model of cerebrovascular hemodynamics that interacts with a pharmacokinetic drug model. We used this model to examine the effects of various stimuli occurring during anesthesia on cerebral blood flow (CBF) and intracranial pressure (ICP). The model is a seven-compartment constant-volume system. A series of resistances and compliances relate blood and cerebrovascular fluid fluxes to pressure gradients between compartments. Variable arterial-arteriolar resistance (Ra-ar) and arteriolar-capillary resistance (Rar-c) simulate autoregulation and drug effects, respectively. Rar-c is also used to account for the effect of CO2 on the cerebral circulation. A three-compartment pharmacokinetic model predicts concentration-time profiles of intravenous induction agents. The effect-site compartment is included to account for disequilibrium between drug plasma and biophase concentrations. The simulation program is written in VisSim dynamic simulation language for an IBM-compatible personal computer. Using the model, we have predicted ICP responses during induction of anesthesia for a simulated patient with normal as well as elevated ICP. Simulation shows that the induction dose of intravenous anesthetic reduces ICP up to 30% (propofol > thiopental > etomidate). The duration of this effect is limited to less than 5 minutes by rapid drug redistribution and cerebral autoregulation. Subsequent laryngoscopy causes acute intracranial hypertension, exceeding the initial ICP. ICP elevation is more pronounced in a nonautoregulated cerebral circulation. Simulation results are in good agreement with the available experimental data. The presented model allows comparison of various drug administration schedules to control ICP.
authors.affiliation: Department of Anesthesiology, New York University Medical Center, New York 10016, USA.
authors.forename: A Y
authors.initials: AY
authors.lastname: Bekker
authors.forename: A
authors.initials: A
authors.lastname: Mistry
authors.forename: A A
authors.initials: AA
authors.lastname: Ritter
authors.forename: S C
authors.initials: SC
authors.lastname: Wolk
authors.forename: H
authors.initials: H
authors.lastname: Turndorf
mesh_terms: D018686:Anesthetics, Intravenous / Q000493:pharmacokinetics*; D001160:Arterioles; D002196:Capillaries; D002560:Cerebrovascular Circulation; D003198:Computer Simulation; D005045:Etomidate / Q000493:pharmacokinetics; D006439:Hemodynamics; D006801:Humans; D007427:Intracranial Pressure / Q000187:drug effects / Q000502:physiology*; D008955:Models, Cardiovascular; D008959:Models, Neurological; D015742:Propofol / Q000493:pharmacokinetics; D013874:Thiopental / Q000493:pharmacokinetics; D014655:Vascular Resistance
chemical_list: D018686:Anesthetics, Intravenous; D013874:Thiopental; D015742:Propofol; D005045:Etomidate