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 [micro sign]g/kg epidural neostigmine (1 [micro sign]g group); 2 [micro sign]g kg epidural neostigmine (2 [micro sign]g group); or 4 [micro sign]g/kg epidural neostigmine (4 [micro sign]g 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. Post-operatively, 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-[micro sign]g group: 529 +/- 314; 2-[micro sign]g group: 504 +/- 284; 4-[micro sign]g 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-[micro sign]g group: 1[1 or 2]; 2-[micro sign]g group: 2[1 or 2]; 4-[micro sign]g 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-[micro sign]g group: 1.6 +/- 1.8; 2-[micro sign]g group: 1.4 +/- 1.6; 4-[micro sign]g group: 2.2 +/- 1.9 (P < 0.005). The incidence of adverse effects was similar among groups (P > 0.05).     

Postoperative analgesia by intraarticular and epidural neostigmine following knee surgery

STUDY OBJECTIVES: To define the analgesic efficacy, and to identify a possible site of action, of epidural and intraarticular neostigmine. DESIGN: Randomized, double-blind study. SETTING: Postoperative 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 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 RESULTS: 56 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. CONCLUSION: Although 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.     

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.     

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 effect of a lidocaine test dose on analgesia and mobility after an epidural combination of neostigmine and sufentanil in early labor

We previously demonstrated the effectiveness of epidural sufentanil and the cholinesterase inhibitor, neostigmine, to initiate selective labor analgesia. Because the traditional lidocaine plus epinephrine test dose (TD) may alter the effect of subsequent epidural drugs, we undertook this investigation to evaluate the impact of a lidocaine TD on analgesia from a combination of epidural neostigmine plus sufentanil administered in early labor. Eighty healthy parturients were randomly allocated to two groups to receive a 3 mL-TD, either lidocaine 2%-epinephrine (1:200,000) or saline-epinephrine (1:200,000), followed 3 min later by epidural neostigmine 500 microg plus sufentanil 10 microg. Pain scores were recorded for 30 min after injection, as was the time elapsed from initial bolus until request for supplemental analgesia. Thirty minutes after injection, adequacy of motor function was evaluated by the parturient's ability to sit, stand up, bend her knees, and walk. Lidocaine TD hastened the onset (5 min vs 15 min) and increased duration (122 +/- 53 min vs 98 +/- 54 min; P = 0.02) of analgesia from epidural neostigmine plus sufentanil bolus. In contrast, the TD did not significantly impair the ability to sit, stand up, or bend the knees. The ability to ambulate, however, was reduced (57% vs 82%; P = 0.04). In conclusion, a traditional lidocaine TD significantly enhances the analgesic effect from the epidural neostigmine plus sufentanil combination, but affects ambulation in early labor.     

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.     

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.     

Caudal neostigmine with bupivacaine produces a dose-independent analgesic effect in children

PURPOSE: To evaluate the analgesic efficacy and duration of varying doses of caudal neostigmine with plain bupivacaine and its side effects in children undergoing genito-urinary surgery. METHODS: In a randomized double-blind prospective study 80 boys aged two to eight years scheduled for surgical repair of hypospadias were allocated randomly to one of four groups (n = 20 each) and received either only caudal 0.25% plain bupivacaine 0.5 mL.kg(-1) (Group I) or 0.25% plain bupivacaine 0.5 mL.kg(-1) with neostigmine (Groups II-IV) in doses of 2, 3 and 4 microg.kg(-1) respectively. Postoperative pain was assessed for 24 hr using an objective pain score. Blood pressure, heart rate, oxygen saturation, total amount of analgesic consumed and adverse effects were also recorded. RESULTS: The duration of postoperative analgesia in Group I (5.1 +/- 2.3 hr) was significantly shorter than in the other three groups (II -16.6 +/- 4.9 hr; III - 17.2 +/- 5.5 hr; IV - 17.0 +/- 5.8 hr; P < 0.05). Total analgesic (paracetamol) consumption was significantly more in Group I (697.6 +/- 240.7 mg) than in the groups receiving caudal neostigmine (II - 248.0 +/- 178.4; III - 270.2 +/- 180.8 and IV -230.6 +/- 166.9 mg; P < 0.05). Groups II, III and IV were comparable with regards to duration of postoperative analgesia and total analgesic consumption (P > 0.05). Incidence of nausea and vomiting were comparable in all four groups. No significant alteration in vital signs or any other adverse effects were observed. CONCLUSIONS: Caudal neostigmine (2, 3 and 4 microg.kg(-1)) with bupivacaine produces a dose-independent analgesic effect ( approximately 16-17 hr) in children as compared to those receiving caudal bupivacaine alone (approximately five hours) and a reduction in postoperative rescue analgesic consumption without increasing the incidence of adverse effects.     

Does clonidine 50 μg improve cervical plexus block obtained with ropivacaine 150 mg for carotid endarterectomy? A randomized,double-blinded study

STUDY OBJECTIVE: To evaluate the effects of adding 50 microg clonidine to 150 mg ropivacaine for superficial cervical plexus block in patients undergoing elective carotid endarterectomy (TEA). DESIGN: Randomized, double-blind study. SETTING: Departments of Anesthesia and Vascular Surgery of a university hospital. PATIENTS: 40 ASA physical status II and III patients undergoing elective TEA during superficial cervical plexus block. INTERVENTIONS: Superficial cervical plexus block was placed using 20 mL of 0.75% ropivacaine alone (Ropi group, n = 20) or with the addition of 50 microg clonidine (Ropi-Clonidine group, n = 20). If required, analgesic supplementation was given with local infiltration with 1% lidocaine and intravenous fentanyl (50-microg boluses). Nerve block profile, need for intraoperative analgesic supplementation, and time to first analgesic request were recorded. MEASUREMENTS AND MAIN RESULTS: Median (range) onset time was 10 minutes (5-25 min) in the Ropi group and 5 minutes (5-20 min) in the Ropi-Clonidine group (P < 0.05). Intraoperative consumption of both 1% lidocaine and fentanyl was higher in patients of the Ropi group (15 mL [0-25 mL] and 250 microg [50-300 microg]) than in patients of the Ropi-Clonidine group (8 mL [0-20 mL] and 0 microg [0-150 microg]; P < 0.05 and P < 0.05, respectively). First postoperative analgesic request occurred after 17 hours (10-24 hrs) in the Ropi group and 20 hours (10-24 hrs) in the Ropi-Clonidine group (P > 0.05). CONCLUSIONS: Adding 50 microg clonidine to 150 mg ropivacaine for superficial cervical plexus block shortened the onset time and improved the quality of surgical anesthesia in patients undergoing elective TEA.     

Small-dose dopamine increases epidural lidocaine requirements during peripheral vascular surgery in elderly patients

We studied 20 patients over the age of 65 yr undergoing prolonged peripheral vascular surgery under continuous lidocaine epidural anesthesia, anticipating that the increased hepatic metabolism caused by small-dose IV dopamine would lower plasma lidocaine concentrations. Subjects were assigned (random, double-blinded) to receive either a placebo IV infusion or dopamine, 2 microg. kg(-1). min(-1) during and for 5 h after surgery. Five minutes after the IV infusion was started, 20 mL of 2% lidocaine was injected through the epidural catheter. One-half hour later, a continuous epidural infusion of 2% lidocaine at 10 mL/h was begun. The epidural infusion was temporarily decreased to 5 mL/h or 5 mL boluses were added to maintain a T8 analgesic level. Arterial blood samples were analyzed for plasma lidocaine concentrations regularly during and for 5 h after surgery. Plasma lidocaine concentrations increased continuously during the epidural infusion and, despite wide individual variation, were similar for the two groups throughout the observation period. During the observation period, the mean maximal plasma lidocaine concentration was 5.8 +/- 2.3 microg/mL in the control group and 5.7 +/- 1.2 microg/mL in the dopamine group. However, the mean hourly lidocaine requirement during surgery was significantly different, 242 +/- 72 mg/h for control and 312 +/- 60 mg/h for dopamine patients (P < 0.03). At the end of Hour 4, the last period when all 20 patients were still receiving the epidural lidocaine infusion, the total lidocaine requirement was significantly different, 1088 +/- 191 mg for the control group and 1228 +/- 168 mg for the dopamine group (P < 0.05). Despite very large total doses of epidural lidocaine (1650 +/- 740 mg, control patients, and 1940 +/- 400, dopamine patients) mean maximal plasma concentrations remained below 6 microg/mL, and no patient exhibited signs or symptoms of toxicity. We conclude that small-dose IV dopamine increased epidural lidocaine requirements, presumably as a consequence of increased metabolism. IMPLICATIONS: We tested dopamine, a drug that increases liver metabolism of the local anesthetic lidocaine to determine if it would prevent excessively large amounts of lidocaine in the blood during prolonged epidural anesthesia in elderly patients. Dopamine did not alter the blood levels of lidocaine, but it did increase the lidocaine dose requirement to maintain adequate epidural anesthesia.     

Determination of the effective therapeutic dose of intrathecal sufentanil for extracorporeal shock wave lithotripsy.

Intrathecal (IT) sufentanil provides effective analgesia for extracorporeal shock wave lithotripsy. However, the optimal dose of sufentanil has not been established. We designed a prospective, randomized, double-blinded study to determine the optimal dose of IT sufentanil. Sixty men were randomized to receive 12.5,15,17.5, or 20 microg of IT sufentanil (n = 15 for each group) via a combined spinal epidural technique. Inadequate analgesia was treated with IV propofol, and the epidural was activated for a pain score greater than 6 on a 10-point verbal analog pain scale. Intraoperative and postoperative visual analog pain scale scores were significantly higher in the 12.5-microg group compared with 20-microg group (3.2 +/- 1.6 vs 1.6 +/- 1.2, P < 0.05, and 1.1 +/- 0.5 vs. 0.5 +/- 0.4, P < 0.05, respectively). The smaller-dosage groups of IT sufentanil required significantly more supplemental boluses of propofol compared with the 20-microg group (67%, 53%, and 40% vs 6%, respectively, P < 0.05). However, pruritus was significantly diminished in the smaller-dosage groups compared with the 20-microg group (55%, 60%, and 67% vs 100%, P < 0.05). The time to discharge was significantly shorter in the 15-microg group compared with the 20-microg group (84 +/- 40 min vs 126 +/- 48 min, P < 0.05). These results suggest that 15 microg of IT sufentanil may be the optimal IT dose for patients undergoing extracorporeal shock wave lithotripsy. IMPLICATIONS: Many anesthetic techniques are used for extracorporeal shock wave lithotripsy (ESWL). We have previously shown that intrathecal sufentanil was effective for ESWL, but was associated with a high incidence of itching. We tested 60 patients in four spinal sufentanil dose groups and found that doses of 15 and 17.5 microg provided the most effective analgesia with the fewest side effects for ESWL, with only mild itching.     

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.     

The effect of intravenous ketoprofen on postoperative epidural sufentanil analgesia in children.

We compared the effect of IV ketoprofen and placebo as an adjuvant to epidural sufentanil analgesia after major surgery. We used a prospective, randomized, double-blinded, placebo-controlled, parallel-group study design in 54 children aged 1-15 yr who received a standardized anesthetic. Either IV ketoprofen or saline was administered in addition to an epidural sufentanil infusion, which was adjusted as required clinically. The study drug infusions were discontinued when pain scores were <3 on 0-10 scale for 6 h at a sufentanil infusion rate of 0.03 microg x kg(-1) x h(-1). Children in the ketoprofen group had a better analgesic effect, as shown by decreased need for sufentanil (mean [10th-90th percentiles] 8.3 [3.1-15.1] microg/kg vs 12.5 [6.2-18.9] microg/kg; P = 0.002) and earlier possibility to discontinuation of the epidural sufentanil (11 [46%] vs 3 [13%]; P = 0.014) before the end of the 72-h study period. In the ketoprofen group, median (range) pain scores were lower during activity at 24 h (2 [0-5] vs 5 [0-7]; P = 0.01) and at 72 h (0 [0-3] vs 2 [0-6]; P = 0.033), and fewer children had inadequate pain relief during activity at 24 h (0 vs 5; P = 0.037). Children who received ketoprofen required fewer infusion rate adjustments (12 [4-20] vs 17 [6-42]; P = 0.016). In the ketoprofen group, the incidence of desaturation (1 [4%] vs 6 [26%]; P = 0.035) and fever (3 [12%] vs 11 [48%]; P = 0.008) was less than that in the placebo group. We conclude that ketoprofen improved postoperative pain in children. IMPLICATIONS: We compared the effect of the IV nonsteroidal antiinflammatory drug ketoprofen versus placebo as adjuvants to epidural opioid analgesia with sufentanil. The continuous IV nonsteroidal antiinflammatory drug improved pain after major surgery in children receiving an epidural opioid. Although ketoprofen reduced epidural sufentanil requirements, the incidence of opioid-related adverse effects was not changed.     

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.     

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 [mu]g epidural clonidine, 750 [mu]g neostigmine, or 75 [mu]g clonidine combined with 250, 500, or 750 [mu]g 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 [mu]g, neostigmine 750 [mu]g, and 75 [mu]g clonidine plus 250 [mu]g neostigmine produced ineffective and short-lasting effects. Clonidine 75 [mu]g plus 500 [mu]g neostigmine and 75 [mu]g clonidine plus 750 [mu]g 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 [mu]g clonidine combined with any dose of neostigmine while maternal sedation (20%) and hypotension (33%) occurred with 150 [mu]g clonidine alone.     

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.     

Transdermal Nitroglycerine Enhances Spinal Neostigmine Postoperative Analgesia following Gynecological Surgery

Background: Intrathecal neostigmine causes analgesia by inhibiting the breakdown of acetylcholine. Experimental data suggest that the production of endogenous nitric oxide is necessary for tonic cholinergic inhibition of spinal pain transmission. The purpose of this study was to determine whether association of transdermal nitroglycerine would enhance analgesia from a low dose of intrathecal neostigmine in patients undergoing gynecologic surgery during spinal anesthesia.

Methods: Forty-eight patients were randomized to one of four groups. Patients were premedicated with use of 0.05-0.1 mg/kg intravenous midazolam and received 15 mg bupivacaine plus 1 ml test drug intrathecally (saline or neostigmine, 5 [mu]g). Twenty to 30 min after the spinal puncture, a transdermal patch of either 5 mg nitroglycerin or placebo was applied. The control (Con) group received spinal saline and transdermal placebo. The neostigmine group received spinal neostigmine and transdermal placebo. The nitroglycerin group received spinal saline and a transdermal nitroglycerine patch. Finally, the neostigmine-nitroglycerin group received spinal neostigmine and transdermal nitroglycerine. Pain and adverse effects were evaluated using a 10-cm visual analog scale.

Results: Patients in the groups were similar regarding age, weight, height, and American Society of Anesthesiologists status. Sensory level to pin prick at 10 min, surgical duration, anesthetic duration, and visual analog scale score for pain at the time of administration of first rescue medication were statistically the same for all groups. The time to administration of first rescue analgesic (min) was longer in the neostigmine-nitroglycerin group (550 min; range, 458-1,440 min; median, 25-75th percentile) compared with the other groups (P < 0.001). The neostigmine-nitroglycerin group required fewer rescue analgesics in 24 h than did the control group (P < 0.0005), whereas the neostigmine group required less analgesics compared with the control group (P < 0.02). The incidence of perioperative adverse effects (nausea, vomiting, headache, back pain) was similar among groups (P > 0.05).     

Does epidural anesthesia have general anesthetic effects? A prospective, randomized, double-blind, placebo-controlled trial

BACKGROUND: Clinically, patients require surprisingly low end-tidal concentrations of volatile agents during combined epidural-general anesthesia. Neuraxial anesthesia exhibits sedative properties that may reduce requirements for general anesthesia. The authors tested whether epidural lidocaine reduces volatile anesthetic requirements as measured by the minimum alveolar concentration (MAC) of sevoflurane for noxious testing cephalad to the sensory block. METHODS: In a prospective, randomized, double-blind, placebo-controlled trial, 44 patients received 300 mg epidural lidocaine (group E), epidural saline control (group C), or epidural saline-intravenous lidocaine infusion (group I) after premedication with 0.02 mg/kg midazolam and 1 microg/kg fentanyl. Tracheal intubation followed standard induction with 4 mg/kg thiopental and succinylcholine 1 mg/kg. After 10 min or more of stable end-tidal sevoflurane, 10 s of 50 Hz, 60 mA tetanic electrical stimulation were applied to the fifth cervical dermatome. Predetermined end-tidal sevoflurane concentrations and the MAC for each group were determined by the up-and-down method and probit analysis based on patient movement. RESULTS: MAC of sevoflurane for group E, 0.52+/-0.18% (+/- 95% confidence interval [CI]), differed significantly from group C, 1.18+/-0.18% (P < 0.0005), and from group I, 1.04+/-0.18% (P < 0.001). The plasma lidocaine levels in groups E and I were comparable (2.3+/-1.0 vs. 3.0+/-1.2 microg/ml +/- SD). CONCLUSIONS: Lidocaine epidural anesthesia reduced the MAC of sevoflurane by approximately 50%. This MAC sparing is most likely caused by indirect central effects of spinal deafferentation and not to systemic effects of lidocaine or direct neural blockade. Thus, lower concentrations of volatile agents than those based on standard MAC values may be adequate during combined epidural-general anesthesia.     

Ropivacaine, 0.1%, plus sufentanil, 0.5 microg/ml, versus bupivacaine, 0.1%, plus sufentanil, 0.5 microg/ml, using patient-controlled epidural analgesia for labor: a double-blind comparison

BACKGROUND: This study compared the administration of 0.1% ropivacaine and 0.5 microg/ml sufentanil with that of 0.1% bupivacaine and 0.5 microg/ml sufentanil via patient-controlled epidural analgesia route during labor. METHODS: Two hundred healthy pregnant women at term with a single fetus with a vertex fetal presentation were randomized in a double-blind fashion to receive either 0.1% ropivacaine and 0.5 microg/ml sufentanil or 0.1% bupivacaine and 0.5 microg/ml sufentanil using a patient-controlled epidural analgesia pump (5-ml bolus dose, 10-min locked-out period, no basal infusion). Pain score on a visual analog scale, Bromage score (0-3), level of sensory block, patient-controlled epidural analgesia ratio, drug use, supplemental boluses, and side effects were recorded at 30 min and then hourly. Mode of delivery, duration of first and second stages of labor, umbilical cord pH, Apgar scores of the newborn, and a measure of maternal satisfaction were recorded after delivery. RESULTS: No differences were seen between the two groups for pain scores on a visual analog scale during labor, volume of anesthetic solution used, mode of delivery, or side effects. Motor block during the first stage of labor was significantly less in the ropivacaine group than in the bupivacaine group (no motor block in 97.8 of patients vs. 88.3%, respectively; P < 0.01). Duration of the second stage of labor was shorter in the ropivacaine group (1.3 +/- 1.0 vs. 1.5 +/- 1.2 h [mean +/- SD]; P < 0.05). Maternal satisfaction was greater in the bupivacaine group (91 +/- 13 mm for contraction, 89 +/- 19 mm for delivery on a visual scale: 0 = not satisfied at all, 100 = fully satisfied) than in the ropivacaine group (84 +/- 21 and 80 +/- 25 mm; P < 0.0001). Patients in the ropivacaine group requested more supplemental boluses to achieve analgesia during the second stage of labor than those in the bupivacaine group (29.7 vs. 19.8%, respectively, requested one or more supplemental boluses; P < 0.05). CONCLUSIONS: Delivered as patient-controlled epidural analgesia, 0.1% ropivacaine and 0.5 microg/ml sufentanil produce less motor block but are clinically less potent than 0.1% bupivacaine and 0.5 microg/ml sufentanil.     

Transdermal Nitroglycerine Enhances Spinal Sufentanil Postoperative Analgesia following Orthopedic Surgery

Background: Sufentanil is a potent but short-acting spinal analgesic used to manage perioperative pain. This study evaluated the influence of transdermal nitroglycerine on the analgesic action of spinal sufentanil in patients undergoing orthopedic surgery.

Methods: Fifty-six patients were randomized to one of four groups. Patients were premedicated with 0.05-0.1 mg/kg intravenous midazolam and received 15 mg bupivacaine plus 2 ml of the test drug intrathecally (saline or 10 [micro sign]g sufentanil). Twenty to 30 min after the spinal puncture, a transdermal patch of either 5 mg nitroglycerin or placebo was applied. The control group received spinal saline and transdermal placebo. The sufentanil group received spinal sufentanil and transdermal placebo. The nitroglycerin group received spinal saline and transdermal nitroglycerine patch. Finally, the sufentanil-nitroglycerin group received spinal sufentanil and transdermal nitroglycerine. Pain and adverse effects were evaluated using a 10-cm visual analog scale.

Results: The time to first rescue analgesic medication was longer for the sufentanil-nitroglycerin group (785 +/- 483 min) compared with the other groups (P < 0.005). The time to first rescue analgesics was also longer for the sufentanil group compared with the control group (P < 0.05). The sufentanil-nitroglycerin group required less rescue analgesics in 24 h compared with the other groups (P < 0.02) and had lesser 24-h pain visual analog scale scores compared with the control group (P < 0.005), although these scores were similar to the sufentanil and nitroglycerin groups (P > 0.05). The incidence of perioperative adverse effects was similar among groups (P > 0.05).