PKsim – Free resource from Anesoft Corporation
The goal of PKsim is to allow anesthesia providers to explore several factors that affect the drug levels of intravenous drugs following a bolus injection. These factors have significant clinical implications. You can explore ideal dosing for the obese patient, pediatric patient, patient with low cardiac output. You can also study the effects of rate of injection.
Note: PKsim is optimized for computer screens and tablets, not phone screens.
PKsim is based on a physiologic-pharmacokinetic model. This model was chosen because it can predict onset of the drug in addition to offset. The physiologic-pharmacokinetic model is similar to Eger’s model used to predict uptake and distribution of inhalation agents.
Assumptions of the Physiologic-Pharmacokinetic Model:
- The drug is injected over time and is added to the mixed venous blood.
- The mixed venous blood flows through the pulmonary circulation to the arterial blood. The graphs plotted in PKsim use the arterial concentration for blood levels.
- Blood flow to each tissue compartment is set in the parameters. The cardiac output is the total tissue blood flow.
- Mixing in each compartment is at equilibrium at the end of each iteration of time, deltaT.
- The tissue/blood constant, T/B, determines the ratio between the concentration of drug in the tissue and the concentration of the blood leaving the tissue.
T/B = Concentration of drug in tissue/Concentration of drug in blood leaving that tissue
- The concentration of the drug in the mixed venous blood is the weighted average of the concentrations leaving the tissue compartments.
- The extraction ratios determine the fraction of drug entering the compartment that is eliminated.
Instructions for PKsim:
Open PKsim in your browser at pksim.anesoft.com.
PKsim is designed to vary model parameters and run experiments. You can run two simulations at once so that you can easily view the results from one clinical scenario vs another. The two simulations are named Control and Experiment.
The tissue/blood coefficients and extraction ratios are initially set to represent propofol. You can change these coefficients to represent other medications such as fentanyl or lidocaine.
The easiest way to set parameters is to select a starting profile similar to the condition you want to simulate. Individual parameters can then be changed to run specific simulated scenarios. You can also modify the injected amounts and duration of injection.
After you set the control and experiment simulation parameters, select the compartment concentrations to display in the plot. Then click the Plot button. The concentrations shown in the plot for each compartment are the concentrations in the blood leaving that compartment. Multiply by the tissue/blood coefficient to obtain the tissue concentration in each compartment.
In addition to the graph, the concentration and time of the peak concentration will be displayed for each compartment. The time for the brain concentration to reach 3mcg/kg (or 3 ng/kg) will also be displayed. This value represents the effective brain concentration for 50% of people to become unconscious. The published range for Ce50 for propofol is 3-10 mcg/mL.