Interactions between epidurally and intrathecally administered sufentanil and bupivacaine in...

The interaction between inactive doses of the opioid sufentanil and the local anesthetic bupivacaine after complexation in various concentrations of hydroxypropyl-beta-cyclodextrin (HP-B-CD) were studied after epidural and intrathecal administration in the rat. Whereas 0.125 microgram sufentanil and 80 micrograms bupivacaine produced only limited effects, a combination of the two compounds resulted in a profound surgical analgesia in all rats tested after epidural administration. Also intrathecally, a clear potentiation was present. The complexation of the same doses of sufentanil plus bupivacaine in HP-B-CD increased the duration of analgesia. Epidurally, a maximal potentiation of analgesia was present at 0.125 microgram sufentanil plus 80 micrograms bupivacaine in 20% HP-B-CD. Intrathecally, maximal potentiation of the analgesic activity was present starting from a complexation of both drugs in 10% hydroxypropyl-beta-cyclodextrin. Higher concentrations of hydroxypropyl-beta-cyclodextrin did not significantly further increase the duration of analgesia. These results indicate that for both routes of spinal administration, the complexation of sufentanil plus bupivacaine in HP-B-CD can produce a longer analgesia than either plain sufentanil, sufentanil combined with bupivacaine or sufentanil alone in HP-B-CD. The complexation of sufentanil plus bupivacaine in HP-B-CD did not diminish the increased safety observed to occur after complexation of sufentanil in HP-B-CD and after combination of sufentanil plus bupivacaine.