Postoperative analgesia by intraarticular clonidine and neostigmine in patients undergoing knee arthroscopy

BACKGROUND AND OBJECTIVE: Clonidine and neostigmine have a central mechanism of analgesic action and are synergistic when given intrathecally. Both drugs also have a peripheral analgesic effect. The purpose of this study was to compare the analgesic effect of intraarticular clonidine and neostigmine, used separately and in combination, in patients undergoing knee arthroscopy. METHODS: Eighty-four American Society of Anesthesiologists (ASA) I and II patients scheduled for meniscus repair under arthroscopy were allocated randomly in 6 groups to receive in a double-blind manner at the end of surgery 150 microg of intraarticular clonidine with subcutaneous saline, 500 microg of intraarticular neostigmine with subcutaneous saline, an intraarticular combination of 150 microg of clonidine and 500 microg of neostigmine with subcutaneous saline, 150 microg of intraarticular clonidine with 500 microg of subcutaneous neostigmine, 500 microg of intraarticular neostigmine with 150 microg of subcutaneous clonidine, or intraarticular and subcutaneous isotonic saline. Postoperative pain scores were measured on a visual analog scale (VAS) at rest and on mobilization. Paracetamol (1 g) was given as a rescue medication when pain score was greater than 40. RESULTS: VAS scores at rest and on mobilization were lower in the first 5 groups compared with the intraarticular saline group (P <.05), but no significant difference was documented between the treated groups. The time to the first paracetamol administration was shorter in the saline group compared with the other groups, and the paracetamol demand was also higher in this group. Forty-five percent of the patients who had received clonidine had at least 1 episode of hypotension versus 4% of those who did not (P <.01). The incidence of bradycardia was 20% and 0%, respectively (P =.01). The incidence of nausea was not statistically different in patients who did and did not receive neostigmine (43% v. 36%, respectively). CONCLUSION: Intraarticular administration of 150 microg of clonidine, 500 microg of neostigmine, or both produce postoperative analgesia, and the combination is not more effective.     

The Effect of Transdermal Nitroglycerin on Spinal S(+)-Ketamine Antinociception Following Orthopedic Surgery

STUDY OBJECTIVES: To determine whether combination of transdermal nitroglycerine (a nitric oxide generator) would enhance analgesia from epidural S(+)-ketamine (a N-methyl-D-aspartate antagonist) in patients undergoing orthopedic surgery with combined spinal anesthesia. DESIGN: Randomized, double-blind study. SETTING: Orthopedic surgery unit of a teaching hospital. PATIENTS: 60 ASA physical status I and II patients scheduled for minor orthopedic knee surgery. INTERVENTIONS: Patients were randomized to one of five groups (n = 12) to receive combined epidural/intrathecal anesthesia. A 10-mL epidural injection was first administered to all patients (study drug or normal saline). Intrathecal anesthesia consisted of 15 mg bupivacaine. Twenty to 30 minutes after the spinal puncture, a transdermal patch of either nitroglycerin 5 mg or placebo was applied. The control group (CG) received epidural saline and transdermal placebo. The nitroglycerin group (NG) received epidural saline and transdermal nitroglycerine patch. The 0.1 mg/kg S(+)-ketamine epidural group (1 KG) received 0.1 mg/kg epidural S(+)-ketamine and transdermal placebo. The 0.2 mg/kg S(+)-ketamine epidural group (2 KG) received 0.2 mg/kg epidural S(+)-ketamine and transdermal placebo. Finally, the nitroglycerin/0.1 mg/kg S(+)-ketamine epidural group (1 NKG) received 0.1 mg/kg epidural S(+)-ketamine and transdermal nitroglycerin. Pain and adverse effects were evaluated using a 10-cm visual analog scale (VAS). MEASUREMENTS AND MAIN RESULTS: The groups were demographically the same. Sensory anesthetic level and VAS score for pain at the time of first rescue medication were similar among groups. The time to first rescue analgesic (min) was less in both the CG and the NG groups compared with the other groups (p < 0.05). Epidural S(+)-ketamine resulted in analgesia to both groups (1 KG < 2 KG; p < 0.05). The 1 NKG and the 2 KG displayed similar analgesia (p > 0.05). The CG required more rescue analgesics in 24 hours compared with the patients who received epidural S(+)-ketamine (p < 0.02). CONCLUSIONS: Epidural S(+)-ketamine resulted in antinociception, which was enhanced by transdermal nitroglycerin.     

The efficacy of thoracic epidural neostigmine infusion after thoracotomy

Few anesthesia studies have explored perioperative continuous epidural infusion of neostigmine. We examined such a regimen in thoracotomy patients. Ninety patients were randomized to one of three groups in this double-blind trial. Before anesthesia induction, an epidural catheter was inserted in all patients at T5-8 levels under local anesthesia. Pre-neo patients received bolus 500-microg epidural neostigmine before anesthesia induction followed by infusion of 125 microg/h until the end of surgery. Post-neo patients received epidural saline during the same time periods plus bolus 500-microg epidural neostigmine at end of surgery. Patients in the control group received saline placebo during all three periods. Patients in the neostigmine groups postoperatively received patient-controlled epidural analgesia with morphine 0.02 mg/mL, bupivacaine 0.08 mg/mL, and neostigmine 7 microg/mL. Control patient-controlled epidural analgesia excluded neostigmine. Data were recorded for 6 postoperative days. Daily patient-controlled epidural analgesia consumption (mL) for Pre-neo patients was significantly less than that of post-neo and control group patients for postoperative days 1-6 (at least 10% and 16% less, respectively; P < 0.05). There was a modest decrease in pain intensity on postoperative days 3-6 for pre-neo patients versus other groups (P < 0.05). These results suggest that continuous thoracic epidural neostigmine started before anesthesia provided preemptive, preventive analgesia and an analgesic-sparing effect that improved postoperative analgesia for these patients without increasing the incidence of adverse effects.     

Low doses of epidural ketamine or neostigmine, but not midazolam, improve morphine analgesia in epidural terminal cancer pain therapy

Study Objective: To examine analgesia and adverse effects of combination epidural pain therapy consisting of administration of morphine with either low dose of ketamine, neostigmine, or midazolam in terminal cancer pain patients.

Design: Randomized double-blind study.

Setting: Teaching hospital.

Patients: 48 terminal cancer patients suffering from chronic pain.

Interventions: Patients were randomized to one of four groups (n = 12). The concept of visual analog scale (VAS), which consisted of a 10-cm line with 0 equaling “no pain at all” and 10 equaling “the worst possible pain” was introduced. All patients were taking oral amitriptyline 50 mg at bedtime. Pain was initially treated with epidural morphine 2 mg twice daily (12-hr intervals) to maintain the VAS below 4/10. Afterwards, VAS scores ≥4/10 at any time were treated by adding the epidural study drug (2 ml), which was administered each morning, just after the 2-mg epidural morphine administration. The control group (CG) received 2 mg of epidural morphine (2 ml). The ketamine group (KG) received 0.2 mg/kg epidural ketamine (2 ml). The neostigmine group (NG) received 100 μg epidural neostigmine (2 ml). The midazolam group (MG) received 500 μg epidural midazolam (2 ml). Patients received the study drugs on a daily basis.

Measurements and Main Results: Duration of effective analgesia was measured as time from the study drug administration to the first patient’s VAS score ≥4/10 recorded in days. The groups were demographically the same. The VAS pain scores prior to the treatment were also similar among groups. Only the patients in the KG demonstrated lower VAS scores compared to the MG (p = 0.018). Time since the epidural study drug administration until patient complaint of pain VAS ≥4/10 was higher for both the KG and NG compared to the CG (KG > CG, p = 0.049; NG > CG; p = 0.0163). Only the KG used less epidural morphine compared to the CG during the period of study (25 days) (p = 0.003).

Conclusion: The association of either low-dose epidural ketamine or neostigmine (but not midazolam) to epidural morphine increased the duration of analgesia in the population studied (gt;20 days) compared to the CG and MG (8 to 10 days) when administered in the early stages of terminal cancer pain therapy, without increasing the incidence of adverse effects.     

Epidural morphine and neostigmine for postoperative analgesia after orthopedic surgery

In this study, we examined the side effects and analgesia of the combination of epidural neostigmine and morphine in patients undergoing orthopedic surgery. Sixty patients undergoing knee surgery were divided into four groups. The intrathecal anesthetic was 15 mg of bupivacaine. The epidural test drug was diluted in saline to a final volume of 10 mL. The control group received saline as the epidural test drug. The morphine group received 0.6 mg of epidural morphine. The neostigmine group (NG) received 60 micro g of epidural neostigmine. The morphine/neostigmine group received 0.6 mg of epidural morphine combined with 60 micro g of epidural neostigmine. The groups were demographically the same and did not differ in intraoperative characteristics. The visual analog scale score at first rescue analgesic and the incidence of adverse effects were similar among groups (P > 0.05). One patient from the NG complained of intraoperative nausea, closely related to spinal hypotension. Postoperatively, two patients from the NG had vomited once. The time (min) to first rescue analgesic was longer in the morphine/neostigmine group ( approximately 11 h) compared with the other groups (P < 0.05). The analgesic consumption (number of analgesic administrations in 24 h) was larger in the control group compared with the other groups (P < 0.05). IMPLICATIONS: The combination of epidural morphine and epidural neostigmine resulted in postoperative analgesia (11 h) devoid of side effects, being an alternative analgesic technique in the population studied.     

Study of three different doses of epidural neostigmine coadministered with lidocaine for postoperative analgesia.

BACKGROUND: Intrathecal neostigmine produces analgesia in volunteers and patients. However, the use of epidural neostigmine has not been investigated. The purpose of the current study was to define the analgesic effectiveness of epidural neostigmine coadministered with lidocaine and side effects in patients after minor orthopedic procedures. METHODS: After Institutional Review Board approval and informed consent, 48 patients (n = 12) undergoing knee surgery were randomly allocated to one of four groups and studied in a prospective way. After 0.05-0.1 mg/kg intravenous midazolam premedication, patients were randomized to receive 20 mg intrathecal bupivacaine plus epidural lidocaine (85 mg) with saline (control group); 1 microg/kg epidural neostigmine (1 microg group); 2 microg/kg epidural neostigmine (2 microg group); or 4 microg/kg epidural neostigmine (4 microg group). 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. Postoperatively, pain was assessed using the visual analog scale, and intramuscular 75 mg diclofenac was available at patient request. RESULTS: Groups were demographically the same and did not differ in intraoperative characteristics (blood pressure, heart rate, ephedrine consumption, oxyhemoglobin saturation, sensory loss before start of surgery, or duration of sensory motor block). The visual analog scale score at first rescue analgesic and the incidence of adverse effects were similar among groups (P > 0.05). The time (min +/- SD) to first rescue analgesic was as follows: control group: 205+/-48; 1-microg group: 529+/-314; 2-microg group: 504+/-284; 4-microg group: 547+/-263 (P < 0.05). The analgesic consumption (number of intramuscular diclofenac injections [mean, 25th-75th percentile]) in 24 h was as follows: control group: 3 [3 or 4]; 1-microg group: 1 [1 or 2]; 2-microg group: 2 [1 or 2]; 4-microg group: 2 [1-3] (P < 0.05). The 24-h-pain visual analog scale score (cm +/- SD) that represents the overall impression for the last 24 h was as follows: control group: 5+/-1.6; 1-microg group: 1.6+/-1.8; 2-microg group: 1.4+/-1.6; 4-microg group: 2.2+/-1.9 (P < 0.005). The incidence of adverse effects was similar among groups (P > 0.05). CONCLUSION: Epidural neostigmine (1, 2, or 4 microg/kg) in lidocaine produced a dose-independent analgesic effect (approximately 8 h) compared to the control group (approximately 3.5 h), and a reduction in postoperative rescue analgesic consumption without increasing the incidence of adverse effects.     

Antinociceptive effect of low-dose intrathecal neostigmine combined with intrathecal morphine following gynecologic surgery

BACKGROUND: The purpose of this study was to determine whether combination of 1-5 microg intrathecal neostigmine would enhance analgesia from a fixed intrathecal dose of morphine. METHODS: A total of 60 patients undergoing gynecologic surgery were randomized to one of five groups. Patients received 15 mg bupivacaine plus 2 ml of the test drug intrathecally (saline, 100 microg morphine, or 1-5 microg neostigmine). The control group received spinal saline as the test drug. The morphine group received spinal morphine as test drug. The morphine + 1 microg neostigmine group received spinal morphine and 1 microg neostigmine. The morphine + 2.5 microg neostigmine group received spinal morphine and 2.5 microg neostigmine. Finally, the morphine + 5 microg neostigmine group received spinal morphine and 5 microg neostigmine. RESULTS: The groups were demographically similar. The time to first rescue analgesic (minutes) was longer for all patients who received intrathecal morphine combined with 1-5 microg neostigmine (median, 6 h) compared with the control group (median, 3 h) (P < 0.02). The morphine group (P < 0.05) and the groups that received the combination of 100 microg intrathecal morphine combined with neostigmine (P < 0.005) required less rescue analgesics in 24 h compared with the control group. The incidence of perioperative adverse effects was similar among groups (P > 0.05). CONCLUSIONS: The addition of 1-5 microg spinal neostigmine to 100 microg morphine doubled the duration to first rescue analgesic in the population studied and decreased the analgesic consumption in 24 h, without increasing the incidence of adverse effects. The data suggest that low-dose spinal neostigmine may improve morphine analgesia.     

The combination of epidural clonidine and S(+)-ketamine did not enhance analgesic efficacy beyond that for each individual drug in adult orthopedic surgery

STUDY OBJECTIVES: To evaluate the benefit of epidural clonidine and S(+)-ketamine combination through the epidural route in adult orthopedic surgery. DESIGN: Randomized double-blinded study. SETTING: Teaching hospital. PATIENTS: Scheduled to undergo knee surgery, 56 American Society of Anesthesiologists physical status 1 and 2 adult patients. INTERVENTIONS: Patients were randomized to 1 of 4 groups to receive the combined epidural-intrathecal technique. A 10-mL epidural injection of either study drug or normal saline was first administered to all patients. Intrathecal anesthesia was performed with 15 mg of bupivacaine. The control group (CG) received epidural saline. The 0.1-mg/kg S(+)-ketamine epidural group received 0.1 mg/kg epidural S(+)-ketamine. The 0.5-microg/kg clonidine epidural group received 0.5 microg/kg epidural clonidine. The S(+)-ketamine/clonidine group received 0.1 mg/kg epidural S(+)-ketamine plus 0.5 microg/kg epidural clonidine. MEASUREMENTS AND MAIN RESULTS: Pain and adverse effects were evaluated by visual analog scale. Rescue analgesics were available to patients. The groups were demographically similar. Sensory level to pinprick, surgical and anesthetic time, and visual analog scale scores for pain at first rescue medication were similar among the groups. The time to first rescue analgesic (minute) was lowest in CG (P < .005). The CG required more rescue analgesics in 24 hours than any of the other groups (P < .0005). Patients who received either epidural clonidine, S(+)-ketamine, or both displayed similar analgesia. The frequency of adverse effects was similar among groups (P > .05). CONCLUSIONS: The association of epidural clonidine or S(+)-ketamine did not result in a greater analgesic effect in the model of acute postoperative pain studied, although the interaction of epidural clonidine and S(+)-ketamine is not attributable to sharing of a common second messenger system.     

Intrathecal bupivacaine with morphine or neostigmine for postoperative analgesia after total knee replacement surgery

PURPOSE: To compare the postoperative analgesic efficacy and safety of intrathecal (IT) neostigmine and IT morphine in patients undergoing total knee replacement under spinal anesthesia. METHODS: Sixty patients scheduled for elective total knee replacement under spinal anesthesia were randomly divided into three equal groups which received IT 0.5% hyperbaric bupivacaine 15 mg with either normal saline 0.5 mL, neostigmine 50 microg, or morphine 300 microg. The maximal level of sensory block, duration of analgesia, time to use of rescue analgesics, the overall 24-hr and four-hour interval visual analogue scale (VAS) pain score, and the incidence of adverse effects were recorded for 24 hr after administration. RESULTS: There was no significant difference in maximal level of sensory block among the three groups. The morphine group had a later onset of postsurgical pain and longer time to first rescue analgesics than the neostigmine group (P <0.05). Overall 24-hr VAS pain scores were significantly higher in the saline group vs the morphine and neostigmine groups (P <0.05). Motor block lasted significantly longer in the neostigmine group than in the morphine and saline groups (P <0.05). The incidence of adverse effects was similar in the neostigmine and morphine groups except for pruritus (70%) occurring more frequently in the morphine group than in the neostigmine and saline groups (0%; P <0.05). Overall satisfaction rates were better in the neostigmine group than in the morphine and saline groups (P <0.05). CONCLUSIONS: IT neostigmine 50 microg produced postoperative analgesia lasting about seven hours with fewer side effects and better satisfaction ratings than IT morphine 300 microg.     

Neostigmine added to bupivacaine in axillary plexus block: which benefit?

INTRODUCTION: Recent study showed that neostigmine (500 microg) by intra-articular produces postoperative analgesia without adverse effect. The author's goal was to determine whether 500 microg of neostigmine added to bupivacaine in axillary plexus block could prolonged postoperative analgesia without increasing the incidence of side effects. METHODS: Ninety patients scheduled for orthopedic or plastic surgery with axillary plexus block were randomly assigned to one of 3 groups : group 1 (TGr n = 30) received saline solution (1 ml) in the axillary plexus, group 2 (NAGr n = 30) received 500 microg (1 ml) neostigmine in the axillary plexus and group 3.500 microg neostigmine subcutaneously (NSGr n = 30). We evaluated visual analog pain scores (VAS), the consumption of the ketoprofene, nausea and vomiting incidence during the first 24 h. ANOVA, Kruskall Wallis and Fisher tests were used for statistical analysis. A p value of <0.05 was considered significant. RESULTS: The VAS score was lower in NAGr (21 +/- 18) vs NSGr (31 +/- 14) and control group TGr (45 +/- 2) (p < 0.05). The consumption of the ketoprofene is 127 +/- 65 mg in NAGr vs 150 +/- 53 mg in NSGr and 200 +/- 50 mg in group TGr (p = 0.02). Incidence of nausea and vomiting was 3.5% in NAGr vs 6.8% in NSGr and 0% for TGr. CONCLUSION: Neostigmine combined to a mixture of lidocaine and bupivacaine prolongs postoperative analgesia after axillary plexus block.     

Postoperative Analgesia by Intra-articular Neostigmine in Patients Undergoing Knee Arthroscopy

Background: Recently, the spinal administration of neostigmine was shown to produce a dose-dependent analgesia. However, this analgesia is limited by adverse effects. The purpose of this study was to examine the analgesic action of peripheral muscarinic receptors by administering intra-articular neostigmine after operation in patients undergoing knee arthroscopy.

Methods: Sixty patients (classified as American Society of Anesthesiologists status I or II) having arthroscopic meniscus repair during general anesthesia were randomized to receive, in a double-blind manner, after operation 125, 250, or 500 micro gram intra-articular neostigmine; 2 mg intra-articular morphine; or as control groups intra-articular saline or 500 micro gram neostigmine given subcutaneously (SC). Visual analog pain scores (VAS), duration of analgesia as defined by first demand for patient-controlled analgesia by morphine, and subsequent 48-h consumption of morphine were evaluated.

Results: Intra-articular (500 micro gram) neostigmine resulted in significant VAS reduction 1 h after injection compared with patients given intra-articular saline and with those given intra-articular morphine. Analgesia lasted longer after 500 micro gram intra-articular neostigmine (350 +/- 126 min) compared with intra-articular morphine (196 +/- 138 min; P < 0.05) or with the control groups (intra-articular saline, 51 +/- 11 min; SC neostigmine, 46 +/- 8 min; P < 0.05). The need for supplementary analgesia was significantly higher in control groups than for patients given intra-articular morphine or 500 micro gram intra-articular neostigmine. No significant analgesic effects were observed for the two lower doses of intra-articular neostigmine. Among all study groups, no adverse effects were observed.     

Continuous epidural analgesia with bupivacaine-fentanyl versus patient-controlled analgesia with i.v. morphine for postoperative pain relief after knee ligament surgery

BACKGROUND: Both epidural analgesia and intravenous patient-controlled analgesia (PCA) have been found efficacious after various types of surgery. We compared the efficacy, safety, side effects and patient satisfaction of these methods in a randomized double-blind fashion after elective anterior cruciate ligament reconstruction of the knee. METHODS: Fifty-six patients had an epidural catheter placed at the L2-L3 interspace. Spinal anaesthesia with 15 mg of plain bupivacaine 5 mg/ml was performed at the L3-L4 interspace. After surgery the patients were randomly divided into three groups: 19 received a continuous epidural infusion with bupivacaine 1 mg/ml and fentanyl 10 mg/ml (F10), 19 patients received bupivacaine 1 mg/ml and fentanyl 5 microg/ml (F5) and 18 patients received saline (S). The rate of the epidural infusions was 0.1 ml kg(-1) h(-1). Each patient could also use an intravenous (i.v.) PCA device with 40 microg/kg bolus doses of morphine with a lockout period of 10 min and a maximum dose 240 microg kg(-1) h(-1). At the end of surgery ketoprofen 100 mg i.v. was given and continued orally three times a day. Patients were assessed for pain with a visual analogue scale (VAS) at rest and during activity, side effects and satisfaction at 3, 9 and 20 h. RESULTS: Both epidural infusions (F10, F5) provided better analgesia than epidural saline plus i.v. PCA (S) (P<0.05). There was slightly less nausea in the S group (NS). In spite of the difference in the quality of pain relief, there was no difference between the groups in patient satisfaction regarding analgesic therapy. CONCLUSION: Epidural infusion of fentanyl (1 microg kg(-1) h(-1) or 0.5 microg kg(-1) h(-1)) and bupivacaine (0.1 mg kg(-1) h(-1)) provided better pain relief but more side effects than intravenous morphine patient-controlled analgesia after knee ligament surgery. Almost all patients in all groups were satisfied with their pain relief.     

新斯的明硬膜外镇痛

目的 探讨新斯的明硬膜外腔注入用于手术后镇痛的剂量依赖性。方法 60例子宫肌瘤切除术或卵巢肿瘤切除术的患者随机分为六组，每组10例，于硬膜外麻醉手术结束时硬膜外腔分别注入新斯的明0.5、1、2或3mg，每组均加东莨菪碱0.3mg和布比卡因0.15mg。测定术后镇痛时间与镇痛强度，并与生理盐水组和0.15mg布比卡因组作比较，结果 新斯的明0.5mg组镇痛时间与镇痛强度不如1mg组（P＜0.05），2mg组和3mg组镇痛时间与镇痛强度与1mg组无明显差异（P＞0.05），生理盐水对照组与布比卡因对照组则无镇痛作用。结论 硬膜外腔注入新斯的明、东莨菪碱、布比卡因混合液，可产生非剂量依赖性镇痛效应。     

Analgesic effect of epidural neostigmine after abdominal hysterectomy

STUDY OBJECTIVE: To evaluate the effects of epidurally administered neostigmine on pain after abdominal hysterectomy. DESIGN: Prospective, randomized, double-blind study. SETTING: Teaching hospital. PATIENTS: 45 ASA physical status I adult patients scheduled for abdominal hysterectomy. INTERVENTIONS: All patients received identical general and epidural anesthesia. At the end of the surgery, they received epidural bupivacaine (10 mg) with either saline (control group, n = 15), 5 micro g/kg (5-micro g group, n = 15), or 10 micro g/kg neostigmine (10-micro g group, n = 15). Postoperatively, 50 mg diclofenac suppository was given for pain relief on patient demand. MEASUREMENTS AND MAIN RESULTS: The time to first diclofenac administration and the number of times diclofenac was required during the first 24 postoperative hours were recorded. Pain was assessed using a 10-cm visual analog pain scale (VAS) at rest at the first diclofenac request, and at 15 and 24 hours after surgery. The time to first diclofenac administration was significantly longer (p < 0.05) in the 10-micro g group (223 +/- 15 min) than in the control (78 +/- 17 min) or 5-micro g groups (88 +/- 18 min). However, epidural neostigmine at both doses did not reduce the number of postoperative diclofenac administrations. There were no differences in VAS among the three groups. CONCLUSIONS: Epidural neostigmine of 10 micro g/kg in bupivacaine provides a longer duration of analgesia than does bupivacaine alone or with 5 micro g/kg of neostigmine after abdominal hysterectomy.     

Epidural administration of neostigmine and clonidine to induce labor analgesia: evaluation of efficacy and local anesthetic-sparing effect

BACKGROUND: Epidural clonidine produces analgesia without motor impairment, and is associated with a local anesthetic-sparing effect during labor. The authors have recently demonstrated that epidural neostigmine initiates selective labor analgesia devoid of adverse effects. Both drugs possess common analgesic mechanisms mediated through spinal acetylcholine release. This study evaluates their epidural combination in parturients. METHODS: At the beginning of labor, parturients were randomly allocated to one of five groups to receive one of the following after a test dose: 150 microg epidural clonidine, 750 microg neostigmine, or 75 microg clonidine combined with 250, 500, or 750 microg neostigmine. A pain score (visual analog scale, 0-100) was recorded before administration and at regular intervals until request for a supplemental injection. Subsequent analgesia was provided by continuous epidural infusion of ropivacaine. RESULTS: Parturients did not differ regarding demographic data and initial pain score. Clonidine 150 microg , neostigmine 750 microg , and 75 microg clonidine plus 250 microg neostigmine produced ineffective and short-lasting effects. Clonidine 75 microg plus 500 microg neostigmine and 75 microg clonidine plus 750 microg neostigmine presented comparable durations of 90 +/- 32 and 108 +/- 38 min (mean +/- SD), respectively, and final analgesic efficacies, with 72.2% and 84%, respectively, of the parturients reporting a visual analog scale score of less than 30 out of 100 after 30 min. Ropivacaine use was significantly reduced in all clonidine groups (average, 9.5 mg/h) in comparison with neostigmine alone (17 +/- 3 mg/h). No adverse effects were observed for 75 mug clonidine combined with any dose of neostigmine while maternal sedation (20%) and hypotension (33%) occurred with 150 microg clonidine alone. CONCLUSIONS: Epidural clonidine, 75 microg , with 750 microg neostigmine is an effective combination to initiate selective labor analgesia without adverse effects. Clonidine use further reduces local anesthetic consumption throughout the course of labor.     

Epidural neostigmine produces analgesia but also sedation in women after cesarean delivery

BACKGROUND: Intrathecal neostigmine produces analgesia but also nausea, limiting its utility. In contrast, epidural administration of neostigmine has been suggested to produce postoperative analgesia without nausea in nonpregnant patients. The purpose of this study was to examine the dose range for efficacy and side effects of epidural neostigmine in women at cesarean delivery receiving combined spinal-epidural anesthesia. METHODS: After institutional approval and informed consent, 80 patients for elective cesarean delivery were given combined spinal-epidural anesthesia with 8 mg hyperbaric bupivacaine plus 10 microg fentanyl. Patients were randomized to receive either saline or 75, 150, or 300 microg neostigmine (n = 20 per group) in 10 ml saline after cord clamping. Pain, morphine consumption, and side effects were monitored for 24 h. RESULTS: Global pain assessment for the first 24 h was reduced from 5.4 +/- 0.2 in the saline group to 3.0-3.5 +/- 0.3 in the neostigmine groups, dose independently. Correspondingly, global satisfaction with neostigmine was also improved (P < 0.05). Nausea and morphine consumption were similar among groups. Intraoperative shivering and sedation were increased in the 300-microg neostigmine group only (P < 0.05), and postoperative sedation was increased by neostigmine in a dose-independent fashion (P < 0.05). CONCLUSIONS: Epidural neostigmine produced modest analgesia in women after cesarean delivery. In contrast with previous reports, which focused primarily on nausea, these data suggest that epidural neostigmine can also produce mild sedation for several hours. These data suggest a limited role for single bolus-administration epidural neostigmine for analgesia after cesarean delivery. They also support future study of epidural neostigmine for obstetric analgesia.     

硬膜外泵入布托啡诺复合小剂量氯胺酮用于妇科患者术后镇痛

目的 观察术后硬膜外持续泵人布托啡诺复合小剂量氯胺酮用于妇科患者术后的镇痛效果.方法 60例ASA Ⅰ或Ⅱ级在腰-硬联合麻醉下行腹式子宫切除的妇科患者术后随机均分为两组,A组为观察组,用布托啡诺0.1 mg/kg 氯胺酮1 mg/kg 生理盐水至100 ml持续泵人;B组为对照组,用布托啡诺0.1 mg/kg 生理盐水至100 ml持续泵入.观察患者术后各时间段的视觉模拟镇痛评分(VAS)、Ramsay镇静评分及对术后镇痛的满意度进行评估,并观察不良反应情况.结果 A组在给药后4 h的VAS低于B组(P<0.05);B组在给药后4、8和12 h的Ramsay镇静评分高于A组(P<0.05),但是两组的评分均在镇静满意的范围.结论 硬膜外持续泵入布托啡诺0.1mg/kg对于妇科术后患者能提供安全有效的镇痛,同时复合小剂量的氯胺酮能增强其镇痛效果,不增加其不良反应的发生.     

Comparison of postoperative analgesic effects of preemptively used epidural ketamine and neostigmine

STUDY OBJECTIVE: To compare the analgesic and side effects of preemptively used epidural ketamine +bupivacaine, neostigmine +bupivacaine, and bupivacaine alone on postoperative analgesia after major abdominal surgery. DESIGN: Randomized, controlled study. SETTING: Inpatient anesthesia at the department of surgery of a metropolitan hospital. PATIENTS: 30 ASA physical status I, II, and III patients scheduled for abdominal surgery. INTERVENTIONS: Group K received 1 mL (50 mg) ketamine and 5 mL (25 mg) bupivacaine epidurally, Group N received 1 mL (0.5 mg) neostigmine and 5 mL (25 mg) bupivacaine epidurally, and Group B received 1 mL saline and 5 mL (25 mg) bupivacaine epidurally 30 minutes before operation. All patients underwent anesthesia induction with thiopental and vecuronium; anesthesia was maintained with isoflorane and vecuronium. For postoperative analgesia, all patients received epidural morphine for 48 hours postoperatively. MEASUREMENTS AND MAIN RESULTS: Standard monitoring included: 48 hours of analgesic requirement, visual analog scale (VAS), mean arterial pressure (MAP), and heart rate (HR) in the 1st, 2nd, 6th, 12th, 24th, and 48th hours. Data were analyzed using Kruskall-Wallis and Mann Whitney U tests, with a p < 0.05 considered statistically significant. No significant differences were observed regarding MAP and HR among the groups during the study period. In Group N, VAS was significantly lower than Group K and Group B. The total opioid consumption in Group N was significantly lower than in Groups K and B in the first 48 hours after the operation. CONCLUSIONS: Preemptive neostigmine can be a good choice for postoperative analgesia.     

No enhancement of sensory and motor blockade by neostigmine added to mepivacaine axillary plexus block.

BACKGROUND: Intrathecal neostigmine induces analgesia but also several side effects. Recently, 500 microg neostigmine administered intraarticularly was shown to produce postoperative analgesia without side effects. The authors' goal was to determine whether 500 microg neostigmine added to mepivacaine in axillary plexus block prolongs postoperative analgesia. In addition, they wanted to determine the incidence of side effects in patients undergoing hand surgery. METHODS: Sixty-nine outpatients scheduled for carpal tunnel syndrome repair with axillary plexus block were randomly assigned to one of three groups that received saline solution in the axillary plexus and subcutaneously (group 1), 500 microg neostigmine in the axillary plexus and saline solution subcutaneously (group 2), or saline solution in the axillary plexus and 500 microg neostigmine subcutaneously (group 3). Sensory and motor block in the four hand nerve distributions were assessed every 5 min for 30 min The duration of the sensory and motor blocks were assessed after operation. Side effects were also recorded. RESULTS: Neostigmine had no effect on sensory and motor block in any of the four nerve distributions, nor did it increase the median duration of sensory block (215 min; range, 120-330 min) compared with group 1 (247 min; range, 190-287 min) or group 3 (236 min; range, 160-280 min). Motor block was slightly shorter (P = 0.045) in group 3 (190 min; range, 135-285 min) compared with group 1 (218 min; range, 145257 min) and group 2 (215 min; range, 105-343 min). Gastrointestinal side effects occurred in 30% of patients in both neostigmine groups but not in group 1 (P < 0.05). CONCLUSIONS: This study suggests that 500 microg neostigmine added to mepivacaine in axillary plexus block does not prolong postoperative sensory block, but it does cause a relatively high incidence of side effects. These two findings raise doubts about the use of neostigmine associated with local anesthetics for plexus neural block.     

Analgesic effect of intraarticular bupivacaine or morphine after arthroscopic knee surgery: a randomized, prospective, double-blind study.

The effect of 20 mL of intraarticular bupivacaine (0.25%, with or without 1:200,000 epinephrine), morphine (0.03%, with or without 1:200,000 epinephrine), or normal saline on postoperative analgesia after arthroscopic knee surgery was studied in a randomized, prospective, double-blind trial in ASA I-III outpatients receiving general anesthesia (n = 112) or regional anesthesia (n = 27 [spinal (n = 25) or epidural (n = 2)]). The visual analogue pain scores in the postanesthesia care unit and 3, 6, 12, and 24 h after surgery, time to first analgesic use, and total 24-h analgesic requirements were recorded. In those who received general anesthesia, the visual analogue scores were significantly lower in the bupivacaine group compared with both the morphine- and placebo-treated patients (P less than 0.05). The time to first analgesic use was longer in both the bupivacaine and morphine groups when compared with the control group (P less than 0.05). No significant differences were detected in total 24-h analgesic requirements among the groups. Patients who had received regional anesthesia had lower visual analogue scores compared with patients who had received general anesthesia irrespective of the intraarticular treatment (P less than 0.05). Our results indicate that intraarticular injection of bupivacaine after arthroscopic knee surgery provides prolonged analgesia but that there is no significant prolonged analgesia provided by intraarticular morphine.