The Pharmacology Of Clonidine Added To Local Anaesthetics

Abstract

Addition of clonidine to local anaesthetic (LA) has been shown to increase its duration of action, but the mechanism by which it does this remains unclear. Some authors have found that, at high concentrations, clonidine causes vasoconstriction and therefore LA remains at its site of action for longer. Other research supports a pharmacodynamic mechanism of action of clonidine involving the cation current Ih. The aim of this study was to test whether adding clonidine to ropivacaine in transversus abdominis plane (TAP) blocks reduced plasma ropivacaine concentrations, indicating that clonidine causes vasoconstriction. The secondary aim was to determine if adding clonidine to ropivacaine enhanced the action of ropivacaine by reducing abdominal wall sensation. In this double-blind randomized controlled trial, consenting patients having laparoscopic gynaecological surgery were allocated to receive TAP blocks with ropivacaine 3 mg/kg plain (control group), ropivacaine 3 mg/kg with 2 mcg/kg clonidine (clonidine group), ropivacaine 3 mg/kg with 1:400,000 adrenaline (adrenaline group), or ropivacaine 3 mg/kg plus a subcutaneous injection of 2 mcg/kg clonidine (SC clonidine group). Total plasma ropivacaine levels were measured over six hours using gas chromatograph mass spectrometry. Abdominal sensation (mechanical, heat, cold) was also measured. Eighty patients were recruited. Groups were similar in terms of age, height, and ASA scores, but patients in the clonidine and SC clonidine groups had higher body weights than patients in the control group. The plasma ropivacaine concentrations of the clonidine and SC clonidine groups were not different from those of the control group. The ropivacaine concentrations of the adrenaline group were lower than the control group from 10 to 90 minutes after TAP block. There were no consistent differences in abdominal wall sensation between groups. While it has been shown to cause vasoconstriction at higher concentrations (10-15 mcg/ml), at a concentration of 1.35 mcg/ml clonidine does not cause vasoconstriction when added to ropivacaine. The mechanism by which clonidine causes prolongation of LA action in the clinical setting is therefore likely to be pharmacodynamic.