[Clonidine increases the anesthetic effectiveness of thiopental]

Treatment with alpha 2-agonists has been demonstrated to improve intra- and postoperative haemodynamic stability. After administration of alpha 2-agonists anaesthetic requirements have been shown to be reduced up to 90% for volatile anaesthetics as well as for intravenous anaesthetics like barbiturates. This study was designed to determine the effect of the alpha 2-agonist clonidine on the anaesthetic potency of the intravenous anaesthetic thiopental in absence of pharmacokinetic influences.

With approval by the local animal care committee all experiments were performed using Xenopus laevis tadpoles in the early pre-limb-bud stage. The animals were exposed to thiopental (0.1-250 microM) or a combination of thiopental (0.1-250 microM) + clonidine (100 microM) for up to 120 min. For each concentration at least ten animals were used. Anaesthesia was defined as loss of righting reflex for 10 s. Based on the response of the tadpoles at different concentrations of the anaesthetic a concentration-response curve was generated according to a method for quantal biologic data and halfmaximal concentrations (EC50) as well as slopes of the curves were calculated. All values are reported as mean +/- sem. Statistical significance was determined by Student's t-test (p < 0.05).

The fraction of anaesthetised animals increased with increasing concentrations of thiopental. The logistic concentration-response plots showed a sigmoidal curve with a slope of 2.14 +/- 0.3. Calculation of the EC50 resulted in a value of 25.5 +/- 2.0 microM. In presence of clonidine thiopental exhibited a left shift of the concentration-response curve with an EC50 of 12.3 +/- 1.6 microM (Slope: 2.75 +/- 0.3).

The presented data confirm the clinical impression that clonidine exercises an anaesthetic sparing effect. Clonidine enhances the anaesthetic potency of thiopental under equilibrium conditions, thus allowing to exclude pharmacokinetic influences as well as excluding effects of adjuvants. It is concluded that the reduction of requirement of anaesthetics by clonidine is due to a pharmacodynamic effect.