Epidural ketamine and its active enantiomer S(+)ketamine have been used intrathecally and epidurally (caudally) for the management of perioperative pain and in a variety of chronic pain syndromes.
Although ketamine has been reported to interact with opioid receptors, binding to local opiate receptors seems to play only a minor role, whereas significant analgesia after even low doses of epidural ketamine is found as a result of antagonism to NMDA receptors.
In vitro and animal data also suggest an involvement of the descending inhibitory pathways, mainly through inhibition of re-uptake of neurotransmitters. The efficacy of extradural ketamine is controversial. Weir and Fee studied the effect of epidural ketamine with three different doses (0.3 mg/kg, 0.5 mg/kg, and 0.65 mg/kg), but did not found any improvement in extradural block.
Overall, the epidural effects of ketamine are relatively small but in combination with other epidural analgesics such as opioids or local anesthetics, an additive or synergistic effect may occur.
Epidural ketamine has been used as an adjuvant to local anesthetic for postoperative analgesia in pediatric patients. Panjabi et al. found the optimal dose of ketamine to be 0.5 mg/kg when added to 0.75 mL/kg bupivacaine of 0.25% for caudal epidural block in pediatric inguinal herniotomy, without an increase in side effects.