• G R Lauretti, R de Oliveira, M V Perez, and C A Paccola.
• Center for Pain Therapy, Hospital das Clínicas, Department of Surgery, Orthopedics and Traumatology, Faculdade de Medicina de Ribeirão Preto-USP, Ribeirão Preto, São Paulo, Brazil.
• J Clin Anesth. 2000 Sep 1;12(6):444-8.

Study ObjectivesTo define the analgesic efficacy, and to identify a possible site of action, of epidural and intraarticular neostigmine.DesignRandomized, double-blind study.SettingPostoperative analgesia, teaching hospital.Patients58 ASA physical status I and II patients undergoing knee surgery.InterventionsAll patients were premedicated with 0.05 to 0.1 mg/kg intravenous midazolam and received combined epidural/intrathecal technique. Intrathecal anesthesia consisted of 20 mg bupivacaine. A 10 mL epidural and intraarticular injection was administered to all patients; this consisted of either the study drug or normal saline. Postoperatively, pain was assessed using the 10 cm Visual Analog Scale (VAS), and intramuscular (IM) 75 mg diclofenac was available at patient request. The control group (CG) received both epidural and intraarticular saline. The 1 microg/kg epidural group (1 microg/kg EG) received epidural neostigmine and intraarticular saline. The 1 microg/kg intraarticular group (1 microg/kg AG) received epidural saline and intraarticular neostigmine. Finally, the 500 microg intraarticular group (500 microg AG) received epidural saline and intraarticular neostigmine.Measurements And Main Results56 patients were evaluated. Groups were demographically the same and did not differ in intraoperative characteristics. The VAS score at first rescue analgesic and the incidence of adverse effects were similar among groups (p< 0.05). The time (min) to first rescue analgesic was shorter for both the CG (228+/-54) and 1 microg/kg AG (251+/-87) groups compared to the 1 microg/kg EG (333+/-78) and 500 microg AG (335+/- 111) groups (p<0.05). The analgesic consumption (number of IM diclofenac injections (mean [25(th)-75(th) percentile]) in 24 hours was higher in the CG group than both the 1 microg/kg EG and 500 microg AG groups (p<0.05). The overall 24-hour pain VAS score (cm) was higher in the CG group than in the 1 microg/kg EG (p<0.05) group.ConclusionAlthough peripheral neostigmine 1 microg/kg did not result in postoperative analgesia, the same dose applied epidurally resulted in over 5 hours of analgesia, similar to a fivefold dose applied peripherally. The results suggest that epidural neostigmine has a greater analgesic efficacy than peripherally applied neostigmine.

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