We thank Drs. Vercauteren and Van de Velde for their interest in our work using intrathecal neostigmine combinations for labor analgesia. We wish to comment on several points raised in their letter. Drs. Vercauteren and Van de Velde are “amazed” that findings from several of our recent studies appear to be contradictory. In one study, 1the addition of 10 μg neostigmine to intrathecal bupivacaine–sufentanil–clonidine did not prolong labor analgesia, yet in a similar study 2using bupivacaine–fentanyl–clonidine, it did. Although these results may appear to be conflicting, they are not.
Drs. Vercauteren and Van de Velde fail to mention that the clonidine dose used in the first study was 50 μg, enough to produce 215 min of analgesia (and an 87% incidence of hypotension). 1This larger dose of clonidine may have overshadowed any benefits that might have been seen from the intrathecal neostigmine. In the second study, 230 μg clonidine was used to minimize hypotension, which was successful (27% incidence). 2By using a lower clonidine dose, the addition of 10 μg neostigmine significantly increased the duration of labor analgesia from 123 to 165 min, but it also produced an unacceptable level of nausea (40%). With the lower dose of clonidine, we were able to observe the analgesic benefits of neostigmine, consistent with other studies from our institution. 3,4Had we used the same clonidine dose for both studies (either 30 or 50 μg) and found varying results, this would imply that the effect of neostigmine was small or variable or that differences existed between study populations.
Our research team works closely together to design complementary studies to expand the pharmacologic knowledge base, with an emphasis on improving the duration and quality of labor analgesia. Although we believe drug combinations offer the best hope of producing prolonged labor analgesia with minimal side effects, we acknowledge the risks of contamination and dilution errors in multiple drug therapy, and we do not advocate this practice for general patient care, as pointed out in editorials by Drs. Eisenach 5and D’Angelo. 6Determining whether drug combinations might be useful and recommending the routine use of such combinations are two different things. If we discover a useful intrathecal or epidural drug combination, we agree with Drs. Vercauteren and Van de Velde—these combinations should be prepared carefully by a hospital pharmacy (which occurs at our institution) or marketed by the pharmaceutical industry, not the individual clinician. It is important to clarify the difference between clinical research and the routine use of a drug combination, and we thank Drs. Vercauteren and Van de Velde for bringing this issue to light.