Principles of TCI
Total intravenous anaesthesia (TIVA) is widely used in human anaesthetic practice, but is much less used in veterinary medicine (Musk, Veterinary Record 2005;157:766-770). Different drug administration protocols can be used to achieve TIVA, and target-controlled infusion (TCI) is designed to achieve and maintain a predicted plasma concentration target (CpT), based on population pharmacokinetics, most often with the use of a computer-programmed syringe pump. The pharmacokinetic profile is programmed into the syringe pump and the rate of infusion is determined by the rate of redistribution and elimination of drug from the body. Usually, 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.
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. 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:
Beths model in dogs (Vet Rec. 2001;148:198-203)
Cattai model for propofol in dogs (Vet Anaesth Analg. 2019;48:568-578)
Bras's method for ke0 determination for Beths model in dogs (J Vet Pharmacol. Therap. 2008;32:182-188)
Cattai model for fentanyl in dogs (Vet Anaesth Analg. 2023;50:31-40)
Model calculations in details
Beths
vc = 0.78 * mass
k10 = 0.07
k12 = 0.0365
k21 = 0.0312
k13 = 0.0049
k31 = 0.0011
Cattai-propofol
vc = 1.48 * (1 + 0.0933 * (mass - 12.25))
k10 = 0.382 * (1 + -0.0111 * (mass - 12.25)) * k_premed * k_ag2
k12 = 0.544
k21 = 0.228
k13 = 0.129 * k_sex * k_ag1
k31 = 0.00993
where the constants are:
k_ag1 (elderly status 1): if (mass<=9 and age>=10) or [(mass>9 and <=25) and age>=9] or [(mass>25 or <=40) and age>=8] or (mass>40 and age>=7) then k_ag1 = 1.347 else k_ag1 = 1
k_ag2 (elderly status 2): if (mass<=9 and age>=11) or [(mass>9 and <=25) and age>=10] or [(mass>25 or <=40) and age>=9] or (mass>40 and age>=8) then k_ag2 = 1.521 else k_ag2 = 1
k_premed: if premedication with acepromazine & methadone then k_premed = 1.209 else k_premd = 1
k_sex: 1 if male, 1-0.345 if female
Cattai-fentanyl
vc = 3.76 * k_sex * Math.pow((mass / 15.1),0.89)
k10 = 0.129
k12 = 0.141
k21 = 0.191
k13 = 0.0771
k31 = 0.01
where k_sex = 1 for male, k_sex = 1.236 for female
