Low-dose spinal neostigmine further enhances the analgesic effect of spinal bupivacaine combined with epidural dexamethasone, following orthopedic surgery

Opioids are considered mainstream for combined spinal-epidural anesthesia, but frequently limited by adverse effects. The aim of this study was to examine whether low-dose spinal neostigmine, epidural dexamethasone or their combination enhances analgesia from spinal bupivacaine without adverse effects. A total of 60 patients undergoing orthopedic surgery were randomized to one of four groups and evaluated for 24-h after surgery for analgesia (time to first rescue analgesic) and rescue analgesic consumption. Patients received 15 mg bupivacaine plus the test drug intrathecally (saline or 1 microgram (μg) neostigmine). The epidural test drug was either saline or 10 mg dexamethasone. The Control group (CG) received spinal and epidural saline. The Neostigmine group (NG), spinal neostigmine and epidural saline; the Dexamethasone group (DG), spinal saline and epidural dexamethasone; and the Neostigmine-dexamethasone group (NDG), spinal neostigmine and epidural dexamethasone. The CG (282 ± 163 min) and NG (524 ± 142 min) were similar in their times to first rescue analgesic and analgesic consumption. The time to first rescue analgesic was longer for the DG (966 ± 397 min) compared with CG and NG (P < 0.0002), and the DG had less ketoprofen consumption and lower overall visual analogue scale-pain sores compared with CG and NG (P < 0.0005). Addition of 1 mg-neostigmine (NDG) resulted in longer time to rescue analgesic (1205 ± 303 min; P < 0.02) and lower ketoprofen consumption (P < 0.05) compared to DG. Sporadic cases of vesical catheterization and emesis were observed, however adverse effects were similar among groups. Spinal 1 microgram (μg) neostigmine further enhanced analgesia from spinal bupivacaine combined with epidural dexamethasone, without increasing the incidence of adverse effects.