Study Objectives: To define the analgesic efficacy, and to identify a possi
ble site of action, of epidural and intraarticular neostigmine.
Design: Randomized analgesia, teaching hospital.
Patients: 58 ASA physical status I and II patients undergoing knee surgery.
Interventions: All patients were premedicated with 0.05 to 0.1 mg/kg intrav
enous midazolam and received combined epidural/intrathecal technique. Intra
thecal anesthesia consisted of 20 mg bupivacaine. A 10 ml. epidural and int
raarticular injection was administered to all patients; this consisted of e
ither the study drug or normal saline. Postoperatively, pain was assessed u
sing the 10 cm Visual Analog Scale (VAS), and intramuscular (IM) 75 mg dicl
ofenac was available at patient request. The control group (CG) received bo
th epidural and intraarticular saline. The 1 mug/kg epidural group (1 mug/k
g EG) received epidural neostigmine and intraarticular saline. The 1 mug/kg
intraarticular group (1 mug/kg AG) received epidural saline and intraartic
ular neostigmine. Finally, the 500 mug intraarticular group (500 mug AG) re
ceived epidural saline and intraarticular neostigmine.
Measurements and Main Results: 56 patients were evaluated. Groups were demo
graphically the same and did not differ in intraoperative characteristics.
The VAS score at first rescue analgesic and the incidence of adverse effect
s were similar among groups (p < 0.05). The time (min) to first rescue anal
gesic was shorter for both the CG (228 +/- 54) and 1 <mu>g/kg AG (251 +/- 8
7) groups compared to the 1 mug/kg EG (333 +/- 78) and 500 mug 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 t
he CG group than both the 1 <mu>g/kg EG and 500 mug AG groups (p < 0.05). T
he overall 24-hour pain VAS score (cm) was higher in the CG group than in t
he 1 <mu>g/kg EG (p < 0.05) group.
Conclusion: Although peripheral neostigmine 1 <mu>g/kg did not result in po
stoperative analgesia, the same dose applied epidurally resulted in over 5
hours of analgesia, similar to a fivefold dose applied peripherally. The re
sults suggest that epidural neostigmine has a greater analgesic efficacy th
an peripherally applied neostigmine. (C) 2000 by Elsevier Science Inc.