Effect of clonidine pre-medication on propofol requirements during lower extremity vascular surgery: A randomized controlled trial

Background. Pre-medication with clonidine reduces the requirement for volatile agents during general anaesthesia. This may also be true for anaesthesia with propofol, but the amount of dose reduction has not been measured. Because clonidine also affects cardiac output and thus regional blood flow it could alter the pharmacokinetics of propofol. This randomized, double-blind placebo-controlled trial aimed to study the effect of clonidine pre-medication on dose requirement for propofol during lower extremity vascular surgery using the bispectral index (BIS) as a measure of anaesthetic depth. Methods. After oral pre-medication with either clonidine 3 μg kg^-1 or placebo, 39 subjects had lower limb vascular surgery using propofol infusion for anaesthesia. Anaesthetic depth was adjusted to a BIS of 45. Predicted plasma propofol concentrations were noted every 30 min from a target-controlled propofol infusion pump and arterial samples were taken at the same time for propofol measurements. Results. Patients in both groups were anaesthetized to similar depths of anaesthesia as indicated by BIS readings (P=0.44). The groups had comparable mean (95% CI) arterial concentrations of propofol, 4.8 (3.5-6.1) μg ml^-1 in the patients given clonidine, and 4.6 (3.4-5.7) μg ml^-1 in the patients given placebo (P=0.81). However, the average plasma concentration predicted by the target-controlled infusion was less in the clonidine group [3.2 (2.9-3.5)] than in the group given placebo [3.6 (3.3-3.9)] μg ml^-1 (P<0.05). Conclusions. Pre-medication with clonidine reduces the requirement for propofol, which is a pharmacokinetic effect and not a pharmacodynamic central sedative effect.