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).     

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 microg 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 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). CONCLUSIONS: Transdermal nitroglycerine alone (5 mg/day), a nitric oxide generator, did not result in postoperative analgesia itself, but it prolonged the analgesic effect of spinal sufentanil (10 microg) and provided 13 h of effective postoperative analgesia after knee surgery.     

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).     

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.     

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.     

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.     

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 [mu]g 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 [mu]g morphine, or 1-5 [mu]g neostigmine). The control group received spinal saline as the test drug. The morphine group received spinal morphine as test drug. The morphine + 1 [mu]g neostigmine group received spinal morphine and 1 [mu]g neostigmine. The morphine + 2.5 [mu]g neostigmine group received spinal morphine and 2.5 [mu]g neostigmine. Finally, the morphine + 5 [mu]g neostigmine group received spinal morphine and 5 [mu]g 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 [mu]g 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 [mu]g 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).     

Efficacy of intrathecal neostigmine for the relief of postinguinal hemiorrhaphy pain

BACKGROUND: Intrathecal administration of various doses of neostigmine has been reported to produce analgesia without neurotoxicity in both animal and human studies. The present study was undertaken to evaluate the efficacy and safety of intrathecal neostigmine for the relief of pain for patients having undergone inguinal herniorrhaphy surgery. METHODS: Sixty men scheduled for elective inguinal herniorrhaphy with spinal anaesthesia were randomly allocated to three groups: group I (n=20) received intrathecal (IT) tetracaine 15 mg, group II (n=20) received IT tetracaine 15 mg+ neostigmine 50 microg, and group III (n=20) received IT tetracaine 15 mg+neostigmine 100 microg. The onset of anaesthesia, duration of analgesia, time to use of first rescue analgesics, the overall 24 h VAS pain scores and the incidence of adverse effects were recorded for 24 h postdrug administration. RESULTS: Onset of anaesthesia (time to T6 sensory block) was significantly faster for group II and III patients compared with group I patients. Motor block (time to lift leg) was greatly prolonged for group III patients, with an average of 6.4 h, compared with 4.1 h for group II patients. Group III patients also showed a later onset of postsurgical pain, lower overall 24-h VAS pain score and prolonged time to first rescue analgesics than did group II patients. There was a significantly greater incidence of adverse effects associated with IT neostigmine, especially nausea and vomiting. CONCLUSION: Our study showed that intrathecal neostigmine at 50 pg or 100 microg enhanced the onset of tetracaine anaesthesia and provided analgesia lasting for 6-9 h, although increased incidences of prolonged motor blockade and nausea or vomiting were noted.     

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.     

The effect of dexamethasone on postoperative pain and emesis after intrathecal neostigmine

We evaluated the effect of a single dose of dexamethasone on the incidence and severity of postoperative nausea and vomiting (PONV) after intrathecal injection of tetracaine plus neostigmine. Sixty ASA physical status I patients scheduled for inguinal herniorrhaphy were studied with a randomized, double-blinded, placebo-controlled protocol. The dexamethasone group (Group D) received 10 mg of dexamethasone IV before performance of spinal anesthesia, whereas the placebo group (Group P) received saline. Spinal anesthesia was performed with intrathecal injection of 15 mg tetracaine plus neostigmine 100 microg in both groups. Pain, PONV, and other side effects were evaluated 24 h after surgery. The duration and severity of analgesia and the incidence of PONV were not significantly different between the two groups. Our results demonstrate that a single dose of dexamethasone (10 mg) did not potentiate the analgesic effect or reduce the incidence of PONV after intrathecal injection of tetracaine and neostigmine. Implications: The results of our evaluation of the effect of IV dexamethasone versus saline control on analgesia and nausea and vomiting after intrathecal neostigmine and tetracaine suggest that IV dexamethasone did not enhance the analgesic effect of neostigmine or reduce the incidence of emesis after intrathecal administration.     

Effects of hyperbaric spinal ropivacaine for caesarean section: with or without fentanyl

BACKGROUND AND OBJECTIVE: Adding various opioids to the local anaesthetic solution administrated intrathecally improves the analgesic potency of spinal analgesia. The purpose of this study was to evaluate the efficacy and safety of intrathecal fentanyl 10 microg added to 15 mg hyperbaric ropivacaine in patients undergoing caesarean section under spinal anaesthesia. METHODS: Thirty-seven healthy, full-term parturients were randomly assigned into two groups: Group S (saline group, n=17) received 15 mg hyperbaric ropivacaine in 2.5 mL + 0.5 mL saline; Group F (fentanyl group, n=20) received 15 mg hyperbaric ropivacaine in 2.5 mL + 10 microg fentanyl in 0.5 mL, intrathecally. Characteristics of spinal block, intraoperative quality of spinal anaesthesia, time to first feeling of pain (complete analgesia), time to first request of analgesics postoperatively (effective analgesia), side-effects and fetal outcomes were evaluated. RESULTS: Regression of sensory block to L5 was significantly prolonged in the fentanyl group compared with the saline group (P = 0.001). Time to the first feeling of pain (130.6 +/- 15.8 min vs. 154.3 +/- 31.1 min; P = 0.008) and the first analgesic requirement (161.2 +/- 32.6 min vs. 213.0 +/- 29.3 min; P < 0.001) were significantly shorter in the saline group compared with the fentanyl group. Side-effects, umbilical arterial and venous blood gases did not differ between the groups. Apgar scores were similar in both groups and no infants had an Apgar score < or =7 at 5 min. CONCLUSIONS: The addition of fentanyl 10 microg, to hyperbaric ropivacaine 15 mg, for spinal anaesthesia increased the duration of analgesia in the early postoperative period in patients undergoing caesarean delivery.     

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.     

Use of intrathecal neostigmine as an adjunct to other spinal medications in perioperative and peripartum analgesia: a meta-analysis

Intrathecal neostigmine has been used as an adjunct to intrathecal local anaesthetic or opioid to prolong regional analgesia and improve haemodynamic stability, with variable results. This meta-analysis aims to evaluate the effectiveness and side-effects of intrathecal neostigmine in the perioperative and peripartum settings. The literature search was based on Cochrane Controlled Trials Register, EMBASE and MEDLINE (from 1966 to 14 November 2003) databases. Volunteer and animal studies were excluded. We identified 26 studies and 19 were considered suitable for detailed data extraction. Intrathecal neostigmine increased the incidence of nausea and vomiting (OR 5.0, 95% CI: 3.4 to 7.3; P<0.00001), bradycardia requiring intravenous atropine (OR 2.7, 95% CI: 1.4 to 5.4; P=0.005), and anxiety, agitation, or restlessness (OR 10.3, 95% CI: 3.7 to 28.9; P=0.00001). It improved the overall 24 hour VAS score (-1.4 VAS pain score, 95% CI: -1.7 to -1.2, P<0.00001), delayed the time of first request for rescue analgesia (168 min, 95% CI: 125 to 211; P<0.00001), and reduced the total number of rescue injections of nonsteroidal anti-inflammatory drug within the first 24 hours (-0.8, 95% CI: -1.1 to -0.4; P=0. 00001). It did not affect the duration of motor blockade (3.5 min, 95% CI: -1.5 to 8.6; P=0.17) or the total amount of ephedrine required (-0.4 mg, 95% CI: -1.5 to 0.7; P=0.5). Adding intrathecal neostigmine to other spinal medications improves perioperative and peripartum analgesia marginally when compared with placebo. It is associated with significant side-effects and the disadvantages outweigh the minor improvement in analgesia achieved.     

A double-blinded,randomized comparison of intrathecal and epidural morphine for elective cesarean delivery

We randomized 150 parturients into a double-blinded trial to receive intrathecal (IT) 100 microg (IT 100 group) or 200 microg (IT 200 group) or epidural 3 mg (Epidural group) of morphine for elective cesarean delivery with a combined spinal/epidural technique. The patients additionally received ketoprofen 300 mg/d. Postoperative pain relief and side effects were registered every 3 h up to 24 h, and all patients were interviewed on the first postoperative day. Pain control was equally good, but the parturients in the IT 100 group requested rescue analgesics more often compared with the other groups (P < 0.05). Itching was a common complaint and was reported by 74% of the parturients in the Epidural group and 65% and 91% in the IT 100 and IT 200 groups, respectively (P < 0.01). Medication for itching was requested by 44%, 24%, and 45% of the patients, respectively (P < 0.05). There was no difference in postoperative nausea or vomiting. The pain relief was perceived as good by >90% of the patients in all groups. In conclusion, because of the decreased incidence of and lesser requirements of medication for itching, IT morphine 100 microg with ketoprofen is recommended in cesarean deliveries. Rescue analgesics nevertheless need to be prescribed. IMPLICATIONS: Spinal morphine is an effective analgesic after cesarean delivery, but it has several side effects. The purpose of this study was to compare the prevalence of side effects and the level of analgesia of epidural morphine with two different doses of spinal morphine after elective cesarean delivery. Although rescue analgesics may be required, intrathecal morphine 100 microg is suggested for postoperative analgesia after cesarean delivery.     

Low-dose intrathecal clonidine combined with sufentanil as analgesic drugs in abdominal gynecological surgery

STUDY OBJECTIVES: To determine whether a low dose of spinal clonidine either alone or combined with sufentanil would provide effective analgesia following abdominal surgery, as a supplement to bupivacaine spinal anesthesia. DESIGN: Randomized double-blind study. SETTING: Gynecological surgery, teaching hospital. PATIENTS: 73 ASA physical status I and II patients undergoing gynecological abdominal surgery with spinal anesthesia. INTERVENTIONS: Patients were randomly assigned to one of four groups and prospectively studied to examine anesthesia, analgesia, and adverse effects. The control group received saline as the test drug; the sufentanil group received 10 microg of sufentanil; the clonidine group received 30 microg of clonidine; and the sufentanil/clonidine group received 5 microg of sufentanil plus 15 microg of clonidine. All groups received intrathecal 15 mg of bupivacaine (3 mL) plus the intrathecal test drug (2 mL). The concept of visual analog scale (VAS) was introduced. All patients were premedicated with intravenous midazolam. Rescue analgesics were available. MEASUREMENTS AND MAIN RESULTS: The groups were demographically the same. Sensory block to pinprick at 10 min was higher for clonidine and sufentanil/clonidine groups compared to the control group (p < 0.02). Anesthetic time (Bromage score 2) was also longer for clonidine and sufentanil/clonidine groups compared to the control and sufentanil groups (p < 0.05). Time to first rescue analgesics was shorter in the control group compared to the other groups (p < 0.02). The number of IM diclofenac dose injections in 24 hours was higher in the control group compared to all other groups (p < 0.05). The incidence of adverse effects and ephedrine consumption were similar among groups. CONCLUSIONS: Intrathecal 15- and 30-microg clonidine doses expanded the anesthesia sensory block and duration of motor block, and provided analgesia.     

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.     

Intrathecal fentanyl-induced pruritus during labour: the effect of prophylactic ondansetron

Fentanyl is commonly used for spinal analgesia during labour but it is associated with a high incidence of pruritus. This randomised, double-blind, placebo-controlled study was performed to evaluate the effect of prophylactic ondansetron on the incidence and severity of pruritus among parturients receiving intrathecal fentanyl as part of combined spinal-epidural analgesia. Seventy-three women were randomised to receive either saline placebo (group P, n = 25), ondansetron 4 mg (group O4, n = 23) or ondansetron 8 mg (group O8, n = 25) intravenously before intrathecal fentanyl 25 micrograms and bupivacaine 2 mg. The incidence and severity of pruritus were measured using a verbal rating and a visual analogue scale, and by the requirement for rescue anti-pruritic medication (naloxone). The overall incidence of pruritus was 95% (group P 100%, group O4 95%, group O8 90%). There were no significant differences between groups for severity of pruritus or requirement for treatment (naloxone given to 45%, 28% and 35% of groups P, O4 and O8 respectively). Secondary outcomes such as the incidence of headache, pain and nausea were not significantly different between groups. We conclude that prophylactic ondansetron 4 or 8 mg intravenously was ineffective in reducing the incidence or severity of intrathecal fentanyl-induced pruritus during labour.     

Preoperative multimodal administration of morphine in arthroscopic surgery

Introduction The aim of the study was to demonstrate the possible effects of preoperative intra-articular, intravenous, or intrathecal administration of morphine on postoperative pain management.Materials and methods Sixty patients undergoing arthroscopic menisectomy were included. Spinal anesthesia was performed in the lateral decubitus position with 3 ml of 0.5% hyperbaric bupivacaine, and the patients were randomized into 4 groups. The IVM (intravenous, iv, morphine) group received 3 mg of iv morphine after completion of spinal anesthesia, the ITM (intrathecal morphine) group received 0.3 mg of morphine together with bupivacaine during spinal anesthesia, the IAM (intra-articular morphine) group received 3 mg intra-articular morphine diluted in 10 ml of saline after spinal anesthesia had been induced but 15 min before surgery, while the C (control) group did not receive any drugs in addition to spinal anesthesia. The sensory block level was determined 15 min after spinal anesthesia. Pain at rest (by visual analogue scale, VAS) and pain at 30° of flexion (by verbal rating scale, VRS) were evaluated during each of the first 2 h of the postoperative period and once every 4 h thereafter until 24 h. In each group; the number of patients in need of analgesics, the timing of the first analgesic intake (duration of analgesia), and the cumulative dose of analgesics were recorded.Results The mean duration of analgesia in the IAM group was significantly longer and the mean analgesic intake was significantly lower when compared with the other groups (p<0.05). The mean VAS value of the ITM group at the 4th postoperative hour was significantly lower than that of the other groups. Mean VAS values at 8 and 12 h and mean VRS values at 4 and 8 h were significantly lower in the ITM and IAM groups (p<0.05). The ITM group had the highest rates of nausea, vomiting, pruritus, and headache (p<0.05).Conclusion It was concluded that the preoperative administration of morphine, either intrathecally or intra-articularly, provides postoperative pain relief. Of these two, the intra-articular route seems to be superior in terms of fewer side-effects (nausea, vomiting, and pruritus), longer duration of analgesia, and reduction of total need for analgesics.     

Efficacy of a low-dose spinal morphine with bupivacaine for postoperative analgesia in children undergoing hypospadias repair

Background:  Children undergoing hypospadias repair need to be protected from highly unpleasant sensory and emotional experiences during and after surgery. We designed a double-blinded, randomized, and placebo-controlled study to compare the efficacy of a low-dose (2 μg·kg⁻¹) of intrathecal morphine with placebo for postoperative pain control of children undergoing repair of hypospadias surgery with spinal anesthesia.
Methods:  Fifty-four children were randomly assigned to one of two spinal anesthesia groups. Group M ( n  = 27) received hyperbaric bupivacaine plus 2 μg·kg⁻¹ of preservative-free morphine and group P ( n  = 27) received hyperbaric bupivacaine plus 0.9% NaCl (placebo) under inhalation anesthesia. General anesthetics were discontinued subsequent to the block. The primary outcome was the presence of pain-requiring analgesics during the first 12 h after the spinal block. Side effects were also recorded. The analgesic effects were evaluated by using the Children's Hospital of Eastern Ontario Pain Scale.
Results:  Forty-nine patients completed the trial. Fifteen patients (60%) in group P received supplementary analgesics within the first 12 h compared to only four patients (16.7%) in group M ( P  = 0.005). Mean duration of analgesia was 480 ± 209 and 720 ± 190 min in group P and group M respectively ( P  = 0.009). The groups were similar in postoperative side effects.
Conclusion:  Spinal anesthesia provided by hyperbaric bupivacaine is adequate for distal hypospadias repair in children, but adding 2 μg·kg⁻¹ intrathecal morphine provides better postoperative pain control when compared to placebo in these children.     

Intrathecal fentanyl added to lidocaine for Cesarean delivery under spinal anesthesia--a randomised clinical trial

The addition of opioids to local anesthetics improves the analgesic potency of spinal analgesia. The purpose of this study was to evaluate the efficacy and safety of intrathecal fentanyl 15 microg when added to lidocaine 80 mg in patients undergoing Cesarean section under spinal anesthesia. Forty healthy parturients scheduled for elective Cesarean section using 80 mg of 5% lidocaine were randomly allocated to additionally 0.9% receive intrathecal fentanyl 15 or saline, as control. Characteristics of spinal block, intraoperative quality of spinal anesthesia, side effects, time of first feeling of pain (complete analgesia) and time to first request of analgesics (effective analgesia) were assessed. Duration of sensory block was prolonged in the fentanyl group (p < 0.05). The quality of intraoperative analgesia was also better. Incidence of side effects did not differ between groups. Duration of complete analgesia (140.2 +/- 29.06 minutes vs 77.90 +/- 20.21 minutes: P < 0.001) and effective analgesia (195.50 +/- 34.06 minutes vs 98.05 +/- 23.48 minutes: P < 0.001) were prolonged in fentanyl group. Adding fentanyl 15 microg to lidocaine 80 mg for spinal anesthesia for Cesarean section, improves the quality of intraoperative analgesia and increases the duration of analgesia in the early postoperative period without increasing maternal or neonatal side effects.