Computer simulations of propofol infusions for total intravenous anaesthesia in dogs

The volatile anaesthetic agents halothane, isoflurane and enflurane are all chlorofluorocarbons and according to international treaties, their emission into the atmosphere will be prohibited from the year 2030. The agents desflurane and sevoflurane are fluorinated hydrocarbons and act as greenhouse gases. The future of veterinary anaesthesia could be dependent on the development of total intravenous anaesthesia. Drugs utilised in total intravenous anaesthesia (TIVA) should have a short duration of action and no tendency to accumulate in the body. Propofol has been the dominant agent used. Computer technology has enabled targeted plasma concentration controlled infusions to replace manual infusion regimens. This study simulated the pharmacokinetics of various infusion regimens similar to those used in clinical practice using previously published pharmocokinetic data. Bolus doses of 0, 4, 6 and 8 mg/kg were simulated in combination with infusion rates of 0, 0.2, 0.3 and 0.4 mg/kg/min for either 240 or 1440 min. The computer was also programmed to maintain a steady state plasma concentration based on the previous simulated data. Generated data were then compared with published data. Changes in the context-sensitive half-life for propofol were also evaluated. Results showed that the generated data were similar to published data. A decrease in plasma concentration to levels associated with a light plane of anaesthesia was evident even when the highest bolus dose and infusion rate were used. There was a slow rise in plasma concentration when only an infusion was used. A lightening of anaesthetic plane may be evident early in the course of TIVA and careful monitoring of anaesthetic depth is required. As the duration of the infusion increased, plasma concentration steadily rose but achieved 95% of the steady state by 204 min. The most dramatic changes in plasma concentration occurred in the first hour of an infusion. Similarly, the infusion rates decreased most in the first 70 min. Most changes in anaesthetic depth are likely to occur early in the course of TIVA and careful observation of anaesthetic depth is required.