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)
Model calculations in details
Marsh
vc = 0.228 * mass;
k10 = 0.119;
k12 = 0.112;
k13 = 0.0419;
k21 = 0.055;
k31 = 0.0033;
ke0 = 1.21;
Schnider
vc = 4.27;
v2 = 18.9-0.391*(age-53);
v3 = 238;
cl1 = 1.89+0.0456*(mass-77)-0.0681*(lbm-59)+0.0264*(height-177);
cl2 = 1.29-0.024*(age-53);
cl3 = 0.836;
k10 = cl1 / vc;
k12 = cl2 / vc;
k13 = cl3 / vc;
k21 = cl2 / v2;
k31 = cl3 / v3;
ke0 = 0.456;
Paedfusor
k12 = 0.114;
k13 = 0.0419;
k21 = 0.055;
k31 = 0.0033;
ke0 = 1.03*Math.exp(-0.12*age);
if (age<13) { vc = 0.458 * mass; k10 = 0.153 * Math.pow(mass, -0.3);}
else if (age>=13 && age<14) {vc = 0.4 * mass; k10 = 0.0678;}
else if (age>=14 && age<15) {vc = 0.342 * mass; k10 = 0.0792;}
else if (age>=15 && age<16) {vc = 0.284 * mass; k10 = 0.0954;}
else if (age>=16) {vc = 0.229 * mass; k10 = 0.119;}
Eleveld (Propofol)
Minto
vc = 5.1-0.0201*(age-40)+0.072*(lbm-55)
v2=9.82-0.0811*(age-40)+0.108*(lbm-55)
v3=5.42
cl1=2.6-0.0162*(age-40)+0.0191*(lbm-55)
cl2=2.05-0.0301*(age-40)
cl3=0.076-0.00113*(age-40)
ke0=0.595-0.007*(age-40)
Eleveld (Remifentanil)
