Clinically useful adjuvants in regional anaesthesia

In this review, emphasis is placed on adjuvant drugs that are already in clinical use. The list of adjuvants studied during the review period includes adrenaline, clonidine, ketamine, neostigmine, nondepolarizing muscle relaxants, and nonsteroidal antiinflammatory drugs. Some future aspects are considered in a couple of experimental studies on slow-release local anaesthetic formulations.

Adrenaline not only acts as a vasoconstrictor, it may also produce analgesia through an alpha2-adrenergic mechanism. Adrenaline may facilitate the uptake of the local anaesthetic into nerves. The addition of adrenaline to a mixture of ropivacaine and fentanyl clearly improves thoracic epidural analgesia. Several recent studies have shown a synergism of clonidine with local anaesthetics in various types of blocks, as well as with spinal opioids. Bradycardia and hypotension may be associated with the use of clonidine. Neostigmine may cause antinociception both in the spinal cord and in peripheral nerves. Neostigmine has been found to potentiate the effect of spinal opioids, but gastrointestinal side effects are frequent. Biodegradable microcapsules containing bupivacaine and dexamethasone have been tested in humans and found to produce analgesia for several days (intercostal block). Local inflammatory reactions and paraesthesias, however, were observed in 30% of cases.

Adrenaline and opioids may be regarded as the best investigated and most important adjuvants in regional anaesthesia. Other drugs, such as clonidine and neostigmine, may prolong analgesia in various regional anaesthetic techniques, but possible side effects may limit their clinical application. Further development is needed concerning extra-long acting analgesic formulations.