Intraarticular Neostigmine and Bupivacaine for Pain Relief after Knee Arthroscopy / 대한마취과학회지

BACKGROUND: Evidence has accumulated that neostigmine can produce potent antinociceptive effects by interacting with muscarinic receptors in peripheral tissues. This study assesses the analgesia and side effects of intraarticular neostigmine alone and the combination of neostigmine and bupivacaine. METHODS: In a double-blind, randomized manner, sixty ASA class 1 or 2 patients were selected for arthroscopic knee surgery under general anesthesia. In the control group (Group 1, n = 15), the patients received 30 ml of intraarticular normal saline. In Group 2 (n = 15), the patients received a combination of intraarticular 500 microgram neostigmine and 30 ml normal saline. In Group 3 (n = 15), 500 microgram neostigmine diluted in 0.125% bupivacaine 30 ml was injected into the knee joint. In Group 4 (n = 15), 750 microgram neostigmine diluted in 30 ml of normal saline was injected into the knee joint. Postoperative pain was assessed using the visual analogue scale (VAS) score at 1, 2, 4, 6, 12, and 24 hours after the intraarticular injection, and the side effects of the four groups were evaluated. RESULTS: Groups 2, 3 and 4 resulted in significantly low VAS scores up to 6 hr after injection compared with Group 1 (P < 0.05). The difference was not significant between Groups 2 and 3, nor between Groups 2 and 4. Side effects such as nausea, vomiting, and urinary retention were observed. However, the intensity of side effect was mild. CONCLUSIONS: The results suggest that intraarticular injection of the acetylcholinesterase inhibitor neostigmine produces a significant analgesic effect following knee arthroscopy. (Korean J Anesthesiol 2000; 39: 212-217)

Postoperative Analgesic Effect of Epidural Neostigmine Coadministered with Bupivacaine under General Anesthesia / 대한마취과학회지

BACKGROUND: Intrathecal injection of analgesic agents such as opioids, clonidine, ketamine and nalbuphine with a local anesthetic produces analgesia in patients. Recently, the analgesic effect of intrathecal neostigmine has been investigated; however, the use of epidural neostigmine has not been investigated. The purpose of this study was to define the analgesic effectiveness and the side effects of epidural neostigmine. METHODS: Forty patients undergoing a total abdominal hysterectomy were divided into 4 groups. After intramuscular 0.1 mg/kg midazolam premedication, patients were randomized to receive epidural bupivacaine with saline (control group), 1 microgram/kg epidural neostigmine (Group I), 2 microgram/kg epidural neostigmine (Group II), or 3 microgram/kg epidural neostigmine (Group III) postoperatively. The concept of the visual analog scale, which consisted of a 10-cm line with 0 equaling "no pain at all" and 10 equaling "the worst possible pain" was introduced. Pain was assessed by using the visual analog scale at 1, 3, 6, 9, 12, and 24 h postoperatively, and intramuscular 90 mg diclofenac was available at the patient's request. RESULTS: The visual analog scale score at first rescue analgesic and the incidence of adverse effects were similar among neostigmine groups. The analgesic consumption in 24 hours and the pain visual analog scale score at 3 h, 12 h, and 24 h were significantly decreased in neostigmine groups compared with control groups. CONCLUSIONS: Epidural neostigmine coadministered with bupivacaine produces a dose-independent analgesic effect compared to the control group and a reduction in postoperative rescue analgesic consumption without increasing the incidence of adverse effects.

Analgesic Effect and Adverse Effects of Intrathecal Neostigmine Used in Spinal Anesthesia for Orthopedic Surgery / 대한마취과학회지

BACKGROUND: Intrathecal injection of analgesic agents sush as opioids, clonidine, ketamine and nalbuphine with a local anesthetic agent during spinal anesthesia for operation is an easy and convenient way to get postoperative analgesia. Intrathecal neostigmine causes an increased ACh concentration in CSF and also has an analgesic effect. This study was designed to examine its postoperative analgesic effect and adverse effects such as nausea/vomiting and urinary retention etc. METHODS: We divided 27 patients who were supposed to receive orthopedic surgery of lower extremities into 3 groups. The control group as injected with heavy bupivacaine 13 mg and normal saline and the N50 and N75 groups were injected with the same amount of bupivacaine combined with neostigmine 50 mcg and 75 mcg respectively. We examined total amount of fluid intake and side effects during operation, and time to first rescue analgesic medication, time to first urination, total applications of rescue analgesic agent, total number of urinary catheterizations for 24 hr after intrathecal injection, and adverse effects of intrathecal neostigmine in the ward. RESULTS: The N75 group showed a significantly longer analgesic duration compared with the control and N50 groups, but the incidence of urinary retention and number of urinary catheterizations increased in the N75 group significantly. Nausea/Vomiting significantly increased in N75 compared with control. Shivering was more common in N50. 2 patients who recieved neostigmine 75 mcg complained of chest discomforts suggesting myocardial ischemia in EKG taken in those episodes. CONCLUSIONS: Neostigmine 75 mcg has better analgesic effect but more frequent adverse effects than control or neostigmine 50 mcg. Therefore, we suggest using high doses of neostigmine cautiously and being aware of its side effects.

Effect of Intrathecal Neostigmine on Post-Cesarean Section Analgesia / 대한마취과학회지

BACKGROUND: Intrathecal (IT) neostigmine produces analgesia in animal and human. This study was designed to evaluate the efficacy and safety of IT neostigmine for post-cesarean section analgesia. METHODS: Forty-five women undergoing cesarean section under spinal anesthesia were randomly assigned into 3 groups to receive; normal saline 0.2 ml, or neostigmine 12.5 microgram, or neostigmine 25 microgram intrathecally with 0.5% hyperbaric bupivacaine 12 mg. Degrees of sensory and motor blocks, maternal hemodynamic changes, and side effects were recorded. Apgar scores and umbilical vein blood gas analysis (UVBGA) were checked for evaluation of fetal status. Postoperative analgesia was provided by intravenous patient-controlled analgesia (PCA) using fentanyl 500 microgram and ketorolac 150 mg in 100 ml. Pain scores with 10-cm visual analogue scale (VAS), time to first PCA use, cumulative PCA consumptions, and side effects were assessed at 1, 2, 4, 8, 12, 24, and 48 hr after IT injection. RESULTS: There were no significant differences among the three groups in characteristics of spinal anesthesia, maternal blood pressure and heart rate, Apgar scores, and UVBGA data. Compared to saline group, IT neostigmine significantly prolonged time to first PCA use and decreased 24 hr- and 48 hr-PCA consumptions (P<0.05). Pain scores in neostigmine groups were significantly lower than those in saline group for first 4 hr after which there were no differences among the three groups. There were significantly higher incidences of nausea and vomiting in neostigmine groups than in saline group. CONCLUSIONS: These data indicate that IT neostigmine can be an alternative postoperative analgesic without adverse fetal effects for cesarean section. However, high incidence of nausea and vomiting seem to limit its clinical usefulness. Further studies are necessary to enhance its analgesic effects and to decrease its adverse effects.

The Effects of Intrathecal Neostigmine on Postoperative Analgesia in Patients Undergoing Total Knee Replacement / 대한마취과학회지

BACKGROUND: Intrathecal neostigmine causes analgesia in dose-dependent pattern. This study was designed to examine postoperative analgesia with intrathecal neostigmine in a randomized, blinded trial with tetracaine as the active control in patients undergoing total knee replacement (TKR). METHODS: Eighty patients scheduled for TKR were divided into seven groups ( Control; no neostigmine, N25, 50, 75, 100, 125 and 150; subarachnoid tetracaine with neostigmine 25, 50, 75, 100, 125 and 150 g, respectively). Postoperatively, patients assessed their pain on a 10-cm visual analog scale (VAS), total analgesic requirement, time to first analgesic rescue medication and side effects were assessed. RESULTS: Increasing doses of intrathecal neostigmine showed a dose-dependent pattern of analgesia defined by the overall VAS scores, time until first administration of rescue analgesic request, and the number of rescue analgesics (p<0.05). Nausea and vomiting was also increased by increasing doses of intrathecal neostigmine (p<0.05). CONCLUSIONS: Intrathecal neostigmine with tetracaine produced definitive analgesia in patients undergoing TKR, and neostigmine 75 g resulted in a better analgesic effect with fewer side effects than other doses.