INTRATHECAL SUFENTANIL AND EPIDURAL BUPIVACAINE FOR LABOR ANALGESIA -DOSE-RESPONSE OF INDIVIDUAL AGENTS AND IN COMBINATION

Backgrounds and Objectives. Combinations of local anesthetics and opio ids are frequently used during spinal and epidural analgesia for the r elief of labor pain. This combination allows for a dose-sparing effect which may reduce potential side effects or toxicity. The precise natu re of the interaction between opioids and local anesthetics in the cli nical setting, i.e., additivity versus synergism, has not been establi shed. This trial was designed to utilize a validated technique of anal ysis of drug interactions, isobolography, to investigate this interact ion. Methods. One hundred healthy laboring patients at term receiving a combined spinal and epidural technique were divided into nine groups as follows. intrathecal sufentanil 2, 5, or 10 mu g (2 mt volume) and epidural saline (10 mL); epidural bupivacaine 5, 12.5, or 25 mg and i ntrathecal saline (2 mt volume); or combination of 1, 2.5, and 5 mu g intrathecal sufentanil plus 2.5, 6.25, or 12.5 mg epidural bupivacaine , using similar volumes, respectively. All drugs were administered in a randomized, double-blind fashion. Pain relief scores were assessed 2 0 minutes after drug injection, and isobolographic analysis was utiliz ed to determine the nature of the interaction. Results. The ED50 of in trathecal sufentanil alone was 2.3 mu g (95% CI 1.7-3.2), and the ED50 for epidural bupivacaine was 24 mg (95% CI 12-50). The combined sufen tanil and bupivacaine fractional dose ED50 (in fractions of the single -dose ED50 values) was found to be approximately one-third and one-ten th of the single drug fractional dose, respectively: sufentanil 0.85 m u g (0.36) and bupivacaine 2.2 mg (0.09). The duration of analgesia wa s nearly equivalent in all sufentanil-done groups (83, 102, and 99 min utes); a dose-response effect was more apparent in the bupivacaine gro up (35, 42, and 74 minutes; P = .006) and the combination group (60, 7 9, 101 minutes: P = .028). Isobolography showed the combination dose t o lie well within the area of synergism: however, the 95% confidence l imits cross the line of additivity thus a pure additive interaction ca nnot be excluded. Conclusions. Markedly reduced doses of these drugs i n combination can be used to provide adequate analgesia during labor c ompared with either single drug done.