Background and objective: Target-controlled infusions of anaesthetic agents have become increasingly available. They can involve the use of propofol in combination with an opioid or a benzodiazepine. The effect site concentration of propofol infusions has been advocated as a method of estimating drug distribution. We investigated the influence of co-induction with remifentanil and midazolam on effect site propofol requirements at induction of anaesthesia using target-controlled infusions.

Methods: Sixty-six consenting adult patients were randomly allocated to three treatment groups. Each group received induction of anaesthesia with a different total intravenous technique. One group was induced with target-controlled propofol alone; another received target-controlled propofol and target-controlled remifentanil (3 ng mL−1); and the last received midazolam (0.03 mg kg−1), target-controlled remifentanil (3 ng mL−1) and target-controlled propofol. Computer simulation was used to calculate effect site concentrations. We recorded propofol dose and effect site concentration at loss of verbal response.

Results: The effect site concentration (Ce50) of propofol alone was 2.19 µg mL−1. This was reduced to 1.55 µg mL−1 during co-induction with remifentanil and further reduced to 0.64 µg mL−1 with midazolam premedication (P < 0.001; ANOVA).

Conclusions: We conclude that co-induction with remifentanil alone or with midazolam can be used to reduce propofol doses at induction of anaesthesia using target-controlled infusions. We believe that using effect site concentration may prove a useful tool in routine clinical practice.

We investigated the effect of a small dose of midazolam, ketamine, droperidol or lidocaine on the propofol dose required for hypnosis during induction of general anaesthesia. These drugs were randomly administered to 100 patients about to undergo scheduled surgery. Propofol was then infused at a rate of 250 μg kg−1 min−1 and the hypnotic dose to produce hypnosis was evaluated. Midazolam (20 μg kg−1) and droperidol (20 μg kg−1) significantly reduced the mean hypnotic dose of propofol (mean) S.D.) compared with the placebo (43.7 ± 17.8 mg, 61.9 ± 10.6 mg and 72.5 ± 27.7 mg after pretreatment with midazolam, droperidol and placebo, respectively), whereas ketamine (0.1 mg kg−1) and lidocaine (1 mg kg−1) did not significantly affect the hypnotic dose of propofol (63.1 ± 25.6 mg and 65.1 ± 24.8 mg, respectively). Only midazolam when compared with saline administration, (176 ± 66s and 298 ± 126s, respectively), shortened the time to achieve hypnosis. The changes in blood pressure (non-invasive) and heart rate were not significantly different in all groups during the induction of anaesthesia and oro-tracheal intubation. These results raise the possibility that new combinations of central nervous system drugs, such as droperidol and propofol, have a potential to reduce the dose of intravenous anaesthetics, including propofol, that produce hypnosis without significant adverse effects.