Evaluation and optimisation of propofol pharmacokinetic parameters in cats for target‐controlled infusion

Abstract

The aim of this study was to develop and evaluate a pharmacokinetic model-driven infusion of propofol in premedicated cats. In a first step, propofol (10 mg/kg) was administered intravenously over 60 seconds to induce anaesthesia for the elective neutering of seven healthy cats, premedicated intramuscularly with 0.3 mg/kg methadone, 0.01 mg/kg medetomidine and 2 mg/kg ketamine. Venous blood samples were collected over 240 minutes, and propofol concentrations were measured via a validated high-performance liquid chromatography assay. Selected pharmacokinetic parameters, determined by a three-compartment open linear model, were entered into a computer-controlled infusion pump (target-controlled infusion-1 (TCI-1)). In a second step, TCI-1 was used to induce and maintain general anaesthesia in nine cats undergoing neutering. Predicted and measured plasma concentrations of propofol were compared at specific time points. In a third step, the pharmacokinetic parameters were modified according to the results from the use of TCI-1 and were evaluated again in six cats. For this TCI-2 group, the median values of median performance error and median absolute performance error were -1.85 per cent and 29.67 per cent, respectively, indicating that it performed adequately. Neither hypotension nor respiratory depression was observed during TCI-1 and TCI-2. Mean anaesthesia time and time to extubation in the TCI-2 group were 73.90 (±20.29) and 8.04 (±5.46) minutes, respectively.

The influence of storage time and temperature on propofol concentrations in canine blood and plasma

“…Although blood has been recommended as the preferred sample for the analysis of propofol concentrations by some authors (Adam et al, 1981; Plummer, 1987; Chan & So, 1990; Zonca et al, 2012; Cattai et al, 2016) the results of the present study indicate a difference between blood and plasma propofol concentrations, at least under the experimental conditions applied in the study. Moreover, the plasma propofol determinations were more consistent than whole blood determinations.…”

“…Propofol is a short-acting intravenous anesthetic, which is associated with smooth and rapid inductions and recovery and is commonly used in dogs and other veterinary patients (Robertson, Johnston & Beemsterboer, 1992; Zoran, Riedesel & Dyer, 1993; Mandsager et al, 1995; Lee et al, 2012; Zonca et al, 2012; Miryabe-Nishiwake et al, 2013; Gomulka et al, 2015; Cattai et al, 2016). Propofol is weakly acidic, and drugs of this type are generally considered to bind to albumin in plasma.…”

“…Data from pharmacokinetic/pharmacodynamics studies based on the relationship between blood propofol concentrations and its effects have been used to design propofol dosage regimens for anesthesia (Cuadrado et al, 1998); however, differences in measured propofol concentrations due to the effects of storage time and temperature on plasma and whole blood samples may influence the dosage regimen design. Blood has been the medium of choice for determining propofol concentrations (Adam et al, 1981; Plummer, 1987; Chan & So, 1990; Zonca et al, 2012; Cattai et al, 2016). However, plasma (or serum) has been used for pharmacokinetic and pharmacodynamics studies, information comparing propofol concentrations in those fluids with whole blood is scarce: in some studies, a plasma/blood ratio of one or less has been described; therefore, propofol may be equally distributed between plasma and blood (Servin et al, 1988; Coetzee et al, 1995; Cuadrado et al, 1998).…”

Target‐controlled infusion in small animals: improving anaesthetic safety

“…Unfortunately, there is very limited information on the pharmacokinetic behaviour of propofol in cats. In a paper summarised on p 503 of this issue of Veterinary Record , Cattai and others (2016) present a first attempt to obtain an adequate pharmacokinetic model for propofol in cats and describes a simple step‐by‐step method to adjust the pharmacokinetic parameters for a standard cat population with the objective of propofol TCI. A population model including more animals would allow for an even more representative set of parameters and would represent further progress.…”