Computer simulation of intracranial pressure changes during induction of anesthesia - Comparison of thiopental, propofol, and etomidate

We have developed a computer model of cerebrovascular hemodynamics that int eracts with a pharmacokinetic drug model. We used this model to examine the effects of various stimuli occurring during anesthesia on cerebral blood f low (CBF) and intracranial pressure (ICP), The model is a seven-compartment constant volume system. A series of resistances and compliances relate blo od and cerebrovascular fluid fluxes to pressure gradients between compartme nts. Variable arterial-arteriolar resistance (Ra-ar) and arteriolar-capilla ry resistance (Rar-c) simulate autoregulation and drug effects, respectivel y. Rar-c is also used to account for the effect of CO2 on the cerebral circ ulation. A three-compartment pharmacokinetic model predicts concentration-t ime profiles of intravenous induction agents. The effect-site compartment i s included to account for disequilibrium between drug plasma and biophase c oncentrations. The simulation program is written in VisSim dynamic simulati on language for an IBM-compatible personal computer. Using the model, we ha ve predicted ICP responses during induction of anesthesia for a simulated p atient with normal as well as elevated ICP. Simulation shows that the induc tion dose of intravenous anesthetic reduces ICP up to 30% (propofol > thiop ental > etomidate), The duration of this effect is limited to less than 5 m inutes 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 circu lation. Simulation results are in good agreement with the available experim ental data. The presented model allows comparison of various drug administr ation schedules to control ICP.