Enhancement of Analgesic Effect of Intrathecal Neostigmine and Clonidine on Bupivacaine Spinal Anesthesia

Background and Objectives Intrathecal administration of neostigmine has been shown to produce analgesia in both animals and humans. The concurrent administration of intrathecal neostigmine and clonidine has been reported to produce no neurotoxicity in sheep. The purpose of the present study was to evaluate the efficacy and safety of the combining intrathecal neostigmine and clonidine for the relief of pain in patients after cesarean delivery. Methods After giving their consents, 80 parturients who were scheduled for cesarean delivery during spinal anesthesia were enrolled by a double-blind randomized design into four groups: bupivacaine group (n = 20) received intrathecal (IT) 10 mg bupivacaine; bupivacaine + neostigmine group (n = 19) received IT 10 mg bupivacaine + 50 μg neostigmine; bupivacaine + clonidine group (n = 20) received IT 10 mg bupivacaine + 150 μg clonidine; and bupivacaine + both (n = 21) received IT 10 mg bupivacaine + 50 μg neostigmine + 150 μg clonidine. The maximum spread of anesthesia, duration of analgesia and motor block, vital signs, and incidence of adverse effects were recorded for 14 hours postinjection. Fifty milligrams intramuscular meperidine was given as a rescue analgesic whenever patient's pain score was greater than 5/10 by the visual analog scale. Results The demographic data were similar for all four groups. Bupivacaine + both group had a significantly higher maximum spread of anesthesia of 23.3 ± 2.9 segments than bupivacaine group of 20.5 ± 2.9 segment. Bupivacaine + both group showed a later onset of postsurgical pain of 6.5 ± 1.5 hours as compared to bupivacaine group of 1.3 ± 0.6 hours. The pain score in bupivacaine + both group was significantly lower than that of bupivacaine group during the first 10 hours. The 24-hour meperidine consumption also was lower in bupivacaine + both group than that of bupivacaine group. However, motor block was significantly prolonged from 3.5 ± 1.1 hours in bupivacaine group to 7.1 ± 1.6 hours in bupivacaine + both group. In addition, other side effects such as nausea and vomiting and dizziness were significantly increased in bupivacaine + both group. Conclusion Our study showed that the combination of 150 μg IT clonidine and 50 μg neostigmine provided longer postsurgical analgesia than with either drug used alone. However, this combination also produced significantly more adverse effects of prolonged motor block and nausea and vomiting. A further study combining the two study drugs but using a lower dose of IT neostigmine (e.g., 25 μg) is recommended.