SimTIVA is a computer simulation program to simulate delivery of total intravenous anaesthesia (TIVA) using a target-controlled infusion (TCI) pump. This progressive web app (PWA) is designed for use on smartphones, tablets and computers.

Written by Terence Luk, 2023. This work is licensed under GNU General Public License v3.0. Read more about the project here, or contact me on Twitter/X for ideas, suggestions or comments. Your advice is greatly appreciated!

Contributors
George Zhong (@propofoldream)
Eric Ng
David Lam

This is an open source project and the source code is published on GitHub.
Last updated 1/11/2024 (V4.85) Build 122.

The purposes are: (1) To simulate TCI/TIVA for educational purposes, and (2) Potentially, to help deliver TCI/TIVA in a low resource setting with no TCI pumps available.
Coding is done in Javascript. The code to the mathematical calculations are based on "STANPUMP", which is freely available from the link below. The pharmacokinetic models available in this program are Marsh, Schnider, Paedfusor and Eleveld for propofol, and Minto and Eleveld for remifentanil. For instructions on using this app, visit the 'Help' page. For documentation of the pharmacological details, visit the 'Documentation' page.

Contact us via our blog page, or get in touch on Twitter/X.

Age (y) 0-100y
Age Actual chronological age	Days Weeks Months Years
Post-menstrual age Covariate for Eleveld; affects clearance in <6mo	weeks What's this?
Weight (kg) 0-200kg, validation with BMI & weight-for-age
Height (cm) 0-250cm, required for Schnider/Eleveld
Gender	Male Female
Model Paedfusor: for children. Marsh/Schnider/Minto: for adults.	Propofol (Marsh) Propofol (Schnider) Propofol (Paedfusor) Propofol (Eleveld) Remifentanil (Minto) Remifentanil (Eleveld) Alfentanil (Maitre) Fentanyl (Shafer) Complex (Dual mode) Propofol (Paedfusor) Propofol (Eleveld) Remifentanil (Eleveld) Complex (Dual mode)
Concomitant opioid	Yes, with opioid No, propofol alone
Concentration (mcg/ml)	5mcg/ml 10mcg/ml 20mcg/ml 25mcg/ml 40mcg/ml 50mcg/ml Custom _mcg/ml
Concentration (mcg/ml)	100mcg/ml 500mcg/ml Custom _mcg/ml
Weight adjusted? If YES: PK model adjusted to BW according to Shibutani, 2004; recommended for obese.	No Yes
Concentration (mcg/ml)	5mcg/ml 10mcg/ml 20mcg/ml 25mcg/ml 50mcg/ml Custom _mcg/ml
Drug dilution (mcg/ml)

Select a SIM-FILE to load:

This will remove all patient data and start SimTIVA all over again. Are you sure?

This will export data to .CSV (comma-separated values): a file that can be opened in any spreadsheet program. The data can be used to plot graphs.

Choose a time resolution (default is 10s) - which is the interval on the x-axis (lower value means more frequent data points). Choose the maximum duration of data capture (default is current time, in seconds); you can set this to up to two hours (7200s) beyond current time.

Time resolution (s)
Max duration (s)

Instructions for use
This is the Quick Start Guide. For details, please visit the separate User Manual.
1. Enter patient data on the first screen you see.
2. Choose a model
3. There are four modes: CP targeting, CE targeting, manual infusion, and intermittent bolus.
4. In addition, there is a Complex mode, which allows simultaneous simulation of propofol and an opioid.

CP/CE targeting mode
1. Enter desired CP/CE target.

2. While you are entering your target, a blue preview box will appear. This will guide your initial bolus and infusion rate.
3. Press Start, when your syringe pump setup is ready to go.
4. The predicted CP and CE will appear on top part of the screen. The 'Graph' section will preview CP/CE of the infusion regimen and the 'Scheme' section will guide you through the next rate changes to achieve and maintain your desired target concentration.

5. When the next rate change is imminent, a red reminder box will appear to notify you of the changes. Make the necessary change on your syringe pump.

Intermittent Bolus Mode
In some settings, such as a short case in a remote location, or in low resource environment, it may not be possible to use any syringe pump at all. With the intermittent bolus mode, a series of repeated small manual boluses are generated, to simulate a target-controlled infusion as close as possible. The accuracy of the repeated intermittent manual bolus scheme is affected by the fluctuation of CE.

Complex mode
In this mode, you may run two-drug simulations simultaneously. For each drug, the functions for CP or CE targeting, manual infusion, or intermittent bolus mode are preserved. In addition, you may explore the pharmacodynamic (PD) interaction between propofol and opioid, as propofol and opioid demonstrate intense synergism. Probability of tolerance to laryngoscopy (PTOL) is used as a measure of potency of propofol-opioid combination. Isobologram charts illustrate the propofol-opioid combinations to achieve the same pharmacodynamic effect.

NB. For the blue preview box, dosage recommendations may be slightly inaccurate because TCI is time-dependent: the moment you enter the target concentration, the preview starts to calculate; but this moment lags behind the moment of real target delivery when you click the 'Update Cpt/Cet' button.

Principles of TCI
TCI, or target-controlled infusions, allow an anaesthetist to enter a desired 'target' concentration to be achieved in the patient's plasma or brain into a computer-programmed syringe pump that utilizes pharmacokinetic models which receive covariates such as age and body weight and then the pump will deliver the desired 'target' concentration accurately, via typically a bolus followed by a decreasing infusion rate. In this SIMTIVA app, it only recommends a bolus/infusion regimen that simulates TCI, but it does not function as a syringe pump, so you have to manually adjust the drug dosages.

The principles, practices and explanations for the pharmacokinetic models are available from this resource: Guidelines for the safe practice of total intravenous anaesthesia (TIVA), by the Association of Anaesthetists and the Society for Intravenous Anaesthesia. https://doi.org/10.1111/anae.14428

A pharmacokinetic model is a mathematical description of the distribution, metabolism and elimination of a drug in the body. The pharmacokinetic behaviour of most anaesthetic drugs used for TIVA can be predicted with a three‐compartment model. The drug is administered into the central compartment (V1), which represents the initial volume of distribution. The second (V2) and third (V3) compartments are mathematical constructs explaining rapid and slow redistribution of drug from V1 into highly perfused and less well perfused tissues, respectively. Rate constants describe the proportion of drug moving between compartments. A summary of the models used for propofol is available from this resource: Principles of total intravenous anaesthesia: basic pharmacokinetics and model descriptions by Al-Rifai Z et al. https://doi.org/10.1093/bjaceaccp/mkv021 In this app, the specific model parameters (vc, v2-3, k10 and other rate constants, ke0) are given in the 'Model parameters' section after initial data entry.

List of references for models:
Marsh - (BJA 1991;67:41-8), 'fast' ke0 (Anesthesiology 2000;92:399-406)
Schnider - (Anesthesiology 1998;88:1170-82)
Paedfusor - (BJA 2003;91(4)507-513), Tpeak method (age-dependent: 0.91min-1 at 1y to 0.15min-1 at 16y) (BJA 2008;100(4):509-516)
Eleveld (Propofol) - (BJA 2018:120:942-959)
Minto - (Anesthesiology 1997;86:10-23)
Eleveld (Remifentanil) - (Anesthesiology 2017;126:1005-18)

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