The effects of combined spinal administration of alpha(2)-adrenoceptor agonists, local anaesthetics, and opioids have been extensively studied. The motor and the sensory block of spinal and epidural anaesthesia is enhanced and prolonged by the combination of clonidine with the local anaesthetics lidocaine, tetracaine and bupivacaine. Because higher plasma levels of local anaesthetics were measured when clonidine was injected epidurally, the enhancement of the local anaesthetic's effect by clonidine is not due to slowed resorption, but rather to direct spinal and supraspinal effects of clonidine. Furthermore, direct local anaesthetic properties of clonidine on nerve fibres are discussed. In addition, in children the combination of clonidine and bupivacaine for caudal anaesthesia resulted in a marked prolongation of postoperative pain relief. Circulatory effects of combined clonidine and local anaesthetics are the result of the specific spinal blockade and the central and peripheral effects of clonidine. The combined epidural and intrathecal administration of opioids and alpha(2)-adrenoceptor agonists provides better postoperative pain relief than the administration of either substance alone. In humans, the interaction seems to be additive rather than supra-additive. Because of its limited duration of action, continuous administration of clonidine is recommended, especially when it is used in combination with opioids. Neither the incidence nor the severity of side effects is increased by a combined therapy with opioids. Despite the sedative properties of clonidine, there is no increased risk of respiratory depression when clonidine is given in combination with opioids. The inhibiting effect on the sympathetic nervous system activity regularly observed during spinal administration of clonidine supports the value of this therapy and will support its use in the future. Therefore, the combination of alpha(2)-adrenoceptor agonists with local anaesthetics or opioids is reasonable and may improve anaesthetic practice.
