Schnider Propofol (SISO)

A single-input single-output physiological simulator for propofol-based anesthesia. The simulator models the pharmacokinetic and pharmacodynamic (PK/PD) response of a patient to an intravenous propofol infusion, with BIS (Bispectral Index) as the observable output.

Overview

Inputs and outputs

Signal	Direction	Units	Description
u_dose	Input	µg/min	Propofol infusion rate commanded by the controller
BIS	Output	0 – 100	Bispectral Index, a measure of anesthetic depth. Target range for surgical anesthesia is 40–60.

Timestep

The simulator runs at a fixed timestep of dt = 0.1 min (6 seconds) over a default duration of 45 min.

PK/PD Model

The simulator implements the Schnider et al. (1998, 1999) three-compartment pharmacokinetic model with an effect-site compartment and a sigmoidal Emax pharmacodynamic model.

Pharmacokinetics (three-compartment)

Propofol distributes across three compartments: plasma (V1), rapidly equilibrating tissue (V2), and slowly equilibrating tissue (V3). The rate constants k10, k12, k21, k13, k31 govern inter-compartmental transfer and elimination.

Effect site

The effect-site concentration Ce lags behind plasma concentration via a first-order equilibration with rate constant ke0. Ce drives the pharmacodynamic response.

Pharmacodynamics (sigmoidal Emax)

BIS is computed from Ce using a sigmoidal Emax model:

$$\text{BIS} = E_0 - E_{\max} \cdot \frac{C_e^{\gamma}}{C_{e50}^{\gamma} + C_e^{\gamma}}$$

Where E0 is the baseline BIS (awake), Emax is the maximum drug effect, Ce50 is the effect-site concentration at half-maximum effect, and γ is the steepness of the curve.

Virtual Patient Cohort

The default cohort (n200) contains 200 virtual patients. Each patient's PK parameters are individualized using the Schnider covariate model, which derives rate constants from:

Age
Weight
Height
Sex
Lean body mass (LBM)

The cohort is sampled to reflect realistic demographic variation in adult surgical patients.

Simulation Features

The following features can be configured in the Simulation Config panel in the IDE:

Feature	Type	Default	Description
noise_enable	`bool`	false	Enable additive Gaussian noise on the BIS measurement
noise_amplitude_min	`float`	0.0	Minimum noise amplitude (BIS units)
noise_amplitude_max	`float`	0.0	Maximum noise amplitude (BIS units)

References

Schnider TW et al. The influence of method of administration and covariates on the pharmacokinetics of propofol in adult volunteers. Anesthesiology. 1998;88(5):1170–1182.
Schnider TW et al. The influence of age on propofol pharmacodynamics. Anesthesiology. 1999;90(6):1502–1516.