Chapter 4

### IMPORTANCE OF SIMULATION

Anesthesiologists use many potent drugs either as single agents or in combination. Each of these drugs has a unique profile in terms of how their concentrations and effects change over time and how they interact with other drugs. Although the basic features of anesthetic drugs are well established, the time course of how the drugs behave, especially in combination with other drugs, is complex and difficult to predict. Anesthesiologists rely on experience and training to formulate dosing regimens, yet they can be confounded by the dynamic changes encountered in the operating room and intensive care unit.

Numerous laboratory investigations have characterized important aspects of drug behavior that are of interest to anesthesiologists. These discoveries often involve complex mathematical formulas and, until recently, have been largely confined to drug package inserts, textbooks, and published manuscripts. With the advent of personal computers and hand-held devices powerful enough to process solutions to these mathematical formulas, models can be used to simulate drug behavior real time and at the point of care.

As a translational tool from laboratory to point of patient care, simulation can be used to visualize drug concentrations and effects over time and how drug combinations influence various drug effects. Figures 4–1 and 4–2 present an example of how simulation illustrates clinical effects of interest. This simulation assumes a 47-year-old, 100-kg, 183-cm male with a history of painful cholelithiasis and anorexia undergoing a laparoscopic cholecystectomy. Propofol, fentanyl, and succinylcholine are used for induction, and sevoflurane, fentanyl, and rocuronium are used for maintenance of anesthesia. Figure 4–1 presents the dosing regimen and the predicted drug effect-site concentrations, and Figure 4–2 presents the predicted drug effects.

###### Figure 4–1

Simulation of drug effect-site concentrations for a combined anesthetic technique using sevoflurane, fentanyl, succinylcholine, and rocuronium. The top section presents the dosing timeline for a 60-minute procedure. Intravenous bolus doses of fentanyl, propofol, succinylcholine, and rocuronium are presented as colored vertical lines. Sevoflurane vaporizer settings are presented in orange. Using published models,1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, and 16 predicted effect-site concentrations (Ce) over time were estimated for each drug and are presented in the 3 plots below the dosing time line: A for sedatives, B for analgesics, and C for neuromuscular blockers. The orange, black, and purple lines represent the Ce values for propofol, sevoflurane, and fentanyl. The dashed black line represents the end tidal sevoflurane concentration. The orange solid and dashed lines represent the Ce values for succinylcholine and rocuronium.

###### Figure 4–2

Predicted drug effects over time. The top section presents the dosing timeline presented in Figure 4–1. Combined effect of propofol, sevoflurane, and fentanyl are presented as a filled-in plot (green), and ...

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