Document Type


Date of Award

Spring 5-31-1997

Degree Name

Master of Science in Biomedical Engineering - (M.S.)


Biomedical Engineering Committee

First Advisor

Alex Y. Bekker

Second Advisor

Arthur B. Ritter

Third Advisor

David S. Kristol


The purpose of this project was to develop a computer model of cerebrovascular hemodynamics interacting with a pharmacokinetic drug model to examine the effects of various stimuli during anesthesia on cerebral blood flow and intracranial pressure.

The mathematical model of intracranial hemodynamics is a seven compartment constant volume system. A series of resistances relate blood and cerebrospinal fluid fluxes to pressure gradients between compartments. Arterial, venous, and tissue compliance are also included. Autoregulation is modeled by transmural pressure dependent arterial-arteriolar resistance. The effect of a drug (thiopental) on cerebrovascular circulation was simulated by a variable arteriolar-capillary resistance. Thiopental concentration, in turn, was predicted by a three-compartment pharmacokinetic model. The effect site compartment was included to account for a disequilibrium between drug plasma and biophase concentrations. The model was validated by comparing simulation results with available experimental observations. The simulation program is written in VisSiM® dynamic simulation language for an IBM-compatible PC.

The model developed was used to calculate cerebral blood flow and intracranial pressure changes which occur during the induction phase of general anesthesia. Responses to laryngoscopy and intubation were predicted for simulated patients with elevated intracranial pressure and nonautoregulated cerebral circulation. Simulation shows that the induction dose of thiopental reduces intracranial pressure up to 15%. The duration of this effect is limited to less than three minutes by rapid redistribution of thiopental and cerebral autoregulation. Subsequent laryngoscopy causes acute intracranial hypertension exceeding the initial intracranial pressure. Further simulation predicts that this untoward effect can be minimized by an additional dose of thiopental administered immediately prior to intubation.

The presented simulation allows comparison of various drug administration schedules to control intracranial pressure and preserve cerebral blood flow during induction of anesthesia. The model developed can be extended to analyze more complex intraoperative events by adding new submodels.



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