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.     

Perioperative intravenous flurbiprofen reduces postoperative pain after abdominal hysterectomy

PURPOSE: To assess whether perioperative intravenous administration of flurbiprofen, a non-steroidal anti-inflammatory drug, reduced postoperative pain after abdominal hysterectomy. METHODS: Forty-five patients undergoing abdominal hysterectomy were randomly assigned to one of three groups of equal size. A control group (CONT) received a placebo 30 min before and at the end of surgery. The other two groups, PRE and POST, received 1 mg x kg(-1) flurbiprofen iv 30 min before and at the end of surgery, respectively. All patients received identical general and epidural anesthesia. Postoperatively, 50 mg diclofenac pr was given for pain relief on patient demand. One of the authors assessed pain using a 10 cm visual analog scale at rest and during coughing at the first request for diclofenac, and at 15, 24, 48, and 72 hr after surgery. The number of times diclofenac was required during the first 24 hr after surgery was also recorded. RESULTS: The number of diclofenac requests in the PRE (1.8 +/- 0.4) and POST groups (2.0 +/- 0.4) were less than in the CONT group (3.0 +/- 0.4). The PRE group showed lower visual analog scale at rest at 15 and 24 hr and on coughing at 24, 48, and 72 hr after surgery than the CONT and POST groups. CONCLUSION: Intravenous 1 mg x kg(-1) flurbiprofen administered during anesthesia reduces postoperative rescue analgesic requirement after abdominal hysterectomy. Moreover, flurbiprofen is more effective when given before than after surgery.     

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.     

Preemptive diclofenac reduces morphine use after remifentanil-based anaesthesia for tonsillectomy

BACKGROUND: We investigated the effect of preincisional rectal diclofenac on pain scores and postoperative morphine requirements of children undergoing tonsillectomy after remifentanil-propofol anaesthesia in a randomized clinical trial. METHODS: Induction and maintenance of anaesthesia were with remifentanil and propofol. Forty children were randomly assigned into two groups before incision. The diclofenac group (n=20) received diclofenac suppositories (approximately 1 mg x kg(-1)) and the control group (n=20) received no treatment. Following discontinuation of remifentanil, patient-controlled analgesia (PCA) with morphine (a loading dose 50 micro g x kg(-1), a background infusion 4 micro g x kg(-1) x h(-1) and a demand dose 20 micro g x kg(-1) with 5-min intervals) was started. We assessed pain score [verbal analogue scales (VAS), 0-10] and sedation level at 5-min intervals and recorded the total morphine consumption of the first hour in the PACU. Patients were discharged to the ward with a new PCA morphine programme (a demand dose 20 micro g.kg-1 with a lockout time of 30 min, for 4 h), and total morphine consumption was recorded. RESULTS: The mean VAS score of the diclofenac group was significantly lower than the control group on arrival in the PACU (2.85 +/- 0.77, 7.60 +/- 0.83, respectively, P < 0.01) and it remained significantly lower in the PACU stay of the children. The mean total morphine consumption of the diclofenac group was less than the control group in the PACU (130.33 +/- 11.26 and 169.92 +/- 9.22, respectively, P=0.012) and the ward (50.80 +/- 11.38 and 87.77 +/- 10.55, respectively, P=0.021). CONCLUSIONS: Preemptive diclofenac given rectally reduced pain intensity and morphine requirements of children anaesthetized with remifentanil for tonsillectomy.     

Caudal neostigmine,bupivacaine, and their combination for postoperative pain management after hypospadias surgery in children

In a randomized, double-blinded study, we examined the analgesic efficacy of caudal neostigmine, bupivacaine, or a mixture of both drugs in 60 children. After the induction of general anesthesia, children were allocated randomly into three groups (n = 20) to receive a caudal injection of either 0.25% bupivacaine 1 mL/kg, with or without neostigmine 2 micro g/kg, or neostigmine 2 micro g/kg in normal saline 1 mL/kg. Intraoperatively, children receiving caudal bupivacaine or a bupivacaine/neostigmine mixture maintained hemodynamic stability, required less inhaled anesthetics, and had a shorter recovery time compared with the caudal neostigmine alone. Postoperatively, the caudal bupivacaine/neostigmine mixture resulted in superior analgesia compared with the other two groups. Recovery to first rescue analgesic times were (mean +/- SD) 22.8 +/- 2.9 h, 8.1 +/- 5.9 h, and 5.2 +/- 2.1 h in the bupivacaine/neostigmine, bupivacaine, and neostigmine groups, respectively (P < 0.001). In addition, the bupivacaine and neostigmine groups received more doses of paracetamol than the bupivacaine/neostigmine group to maintain adequate analgesia in the first 24 postoperative h. Postoperative vomiting occurred in 25%, 10%, and 30% in the caudal bupivacaine/neostigmine, bupivacaine, and neostigmine groups, respectively (P < 0.01). We conclude that caudal neostigmine 2 micro g/kg provides postoperative analgesia comparable to caudal bupivacaine in children undergoing hypospadias repair surgery. IMPLICATIONS: Caudal neostigmine 2 micro g/kg provides postoperative analgesia comparable to caudal bupivacaine in children undergoing hypospadias repair surgery. Co-administration of the two drugs is associated with extended postoperative analgesia and reduced need for supplementary analgesics.     

Wound instillation with 0.25% bupivacaine as continuous infusion following hysterectomy

Postoperative pain relief was assessed by the effects of local anesthetic wound instillation on 100 patients who had undergone total abdominal hysterectomy with bilateral salpingo oophorectomy (TAH with BSO). Patients were divided into four groups of wound and non-wound instillation: Wound instillation Group A1 received diclofenac IM. Group A2 received diclofenac suppository. Non-wound instillation Group B1 received diclofenac IM. Group B2 received diclofenac suppository. A standard general anesthesia technique was administered. For would instillation, a multiholed (1 cm apart) 18G epidural catheter was placed above rectus sheath. This was connected to a pediatric regulated drip set with "Dial-a flo" to deliver 0.25% bupivacaine 10 ml/hour for 6 hours after a basal bolus of 10 ml. During first 6 hours after surgery rescue pentazocine 15 mg was administered to achieve VAS score < or = 30. Thereafter, rescue diclofenac was administered to patients. The requirement of rescue analgesic (pentazocine) was significantly less (P < 0.001) in wound instillation Groups A1 (13.80 mg +/- 13.64) and A2 (12.00 mg +/- 12.25) in comparison to non wound instillation Groups B1 (35.60 mg +/- 14.02) and B2 (31.80 mg +/- 15.80). Rescue diclofenac was not required in wound instillation groups as compared to 30 mg (B1) and 36 mg (B2) in non wound instillation groups. Nausea and vomiting was less in wound instillation groups. VAS score supine from 4th to 12th hours, VAS coughing during all time interval and VAS leg raising from 3rd to 12th hours was significantly lower (P < 0.001) in wound instillation group (A1, A2) in comparison to non wound instillation groups (B1, B2). We conclude that basal bolus infusion followed by continuous wound instillation of bupivacaine decreases analgesic requirement and pain scores in first 24 hours of postoperative period after TAH with BSO.     

Prophylactic Use of Epidural Mepivacaine/Morphine, Systemic Diclofenac, and Metamizole Reduces Postoperative Morphine Consumption after Major Abdominal Surgery

Background: Surgical trauma induces nociceptive sensitization leading to amplification and prolongation of postoperative pain. While preemptive analgesic treatment with numerous agents has been successful in experimental animals, results of human studies remain conflicting. The authors used a multimodal approach for preemptive analgesia before abdominal surgery: diclofenac and metamizole inhibit prostaglandin synthesis, thus influencing peripheral sensitization; epidural local anesthetics induce conduction block, epidural opioids inhibit nociceptive synaptic transmission, and metamizole induces descending inhibition. The interaction of these drugs might suppress spinal nociceptive sensitization and postoperative analgesic demand.

Methods: One hundred forty-two patients scheduled for major abdominal surgery were randomly assigned to one of three groups and studied prospectively. Epidural catheters in groups 1 and 2 were placed at interspaces T8-T10, the position of the catheter was confirmed by epidurography, and sensory testing after administration of 5 ml mepivacaine 1%. Group 1 received 75 mg intramuscular diclofenac, 1000 mg intravenous metamizole, 5.3+/-1 mg epidural morphine, and 15-20 ml mepivacaine 1% 85+/-41 min before skin incision. Epidural analgesia was maintained by injections of 0.1 ml *symbol* kg sup -1 *symbol* h sup -1 mepivacaine 1%. Group 2 patients received the balanced analgesia regimen before wound closure (221+/-86 min after skin incision). Group 3 patients did not receive any study substances. General anesthesia was induced with 5 mg/kg thiopental and 2 micro gram/kg fentanyl and maintained with enflurane and nitrous oxide. Postoperative analgesia consisted of patient-controlled intravenous morphine over 5 days.

Results: Median visual analog scale pain intensities were < 3 cm and did not differ among the groups. Morphine consumption per hour on postoperative day 2 was 0.8+/-0.1 mg/h (group 1) < 1.2+/- 0.1 mg/h (group 2) = 1.1+/-0.1 mg/h (group 3) and cumulative morphine consumption (in mg) on the morning of day 5 was 95+/-9 (group 1) < 111+/-11 (group 2) < 137+/-10 (group 3).     

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.     

Efficacy of ropivacaine, bupivacaine, and levobupivacaine for labor epidural analgesia

STUDY OBJECTIVE: To compare analgesic efficacy and intensity of motor block with continuous infusions of ropivacaine, bupivacaine, and levobupivacaine in combination with fentanyl for labor epidural analgesia. DESIGN: Prospective, randomized, double-blinded study. SETTING: Labor and delivery suite at Magee Womens Hospital, Pittsburgh, PA. PATIENTS: 162 ASA physical status I and II, full-term, primiparous women. INTERVENTIONS: All patients received epidural labor analgesia. Epidural medication consisted of an initial bolus of 8 mL local anesthetic with fentanyl (100 microg) followed by an infusion at 12 mL/h of local anesthetic with 2 microg/mL fentanyl. Patients were allocated to one of three groups, as follows: group 1 received bolus and infusion of bupivacaine 0.125%, group 2 received bolus and infusion of levobupivacaine 0.125%, and group 3 received a bolus of ropivacaine 0.2% and infusion of ropivacaine 0.1%. MEASUREMENTS: Maternal vital signs, pain visual analog scale (VAS) score, sensory levels, and motor block (Bromage score) were recorded every hour. Duration of first and second stage of labor and mode of delivery were also recorded. RESULTS: There were no statistically significant differences in pain VAS or Bromage motor scores among the three groups of patients at any of the measured time intervals. The time to achieve T10 sensory level and patient comfort was shorter in the ropivacaine (9.35 +/- 4.96 min) and levobupivacaine (9.56 +/- 4.71 min) groups than the bupivacaine (11.89 +/- 7.76 min) group, although this difference did not reach a statistically significant level (P = 0.06). The second stage was significantly shorter in the bupivacaine group, lasting 81.27 +/- 63.3 min, compared with the ropivacaine group (121.69 +/- 86.5 min) and the levobupivacaine (115.5 +/- 83.6 minutes) group (P = 0.04). CONCLUSION: There are no significant differences in pain VAS and Bromage scores between 0.1% ropivacaine, 0.125% bupivacaine, and 0.1% levobupivacaine given for labor epidural analgesia.     

Effects of epidural bupivacaine and epidural morphine on bowel function and pain after hysterectomy

A comparison was made of the effects of continuous epidural analgesia with bupivacaine and intermittent epidural morphine on bowel function after abdominal hysterectomy. The duration of postoperative ileus was assessed as the time from the end of operation to the first postoperative passage of flatus and feces. Twenty-two patients were randomly allocated to two equal groups. An "epidural morphine" group received general anesthesia and epidural morphine for postoperative pain relief, and an "epidural bupivacaine" group was given combined general anesthesia and epidural anesthesia with 0.5% bupivacaine intraoperatively and epidural analgesia with 0.25% bupivacaine postoperatively. Epidural morphine or bupivacaine was given for 42 h postoperatively. Pain intensity (visual analog scale) was low in both groups, but lower (P less than 0.05) in the epidural bupivacaine group. The time to first passage of flatus was 22 +/- 16 h in the epidural bupivacaine group and 56 +/- 22 h in the epidural morphine group (P less than 0.001). The time to first postoperative passage of feces was shorter (P less than 0.05) in the former than in the latter 57 +/- 44 h vs 92 +/- 22 h). The patients of the epidural bupivacaine group started intake of oral fluids earlier (P less than 0.01) and to a greater extent (P less than 0.05) than those in the epidural morphine group. It is concluded that the duration of postoperative ileus after hysterectomy is shorter when epidural bupivacaine is given for postoperative pain relief than when this is achieved by epidural morphine.     

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 [mu]g fentanyl. Patients were randomized to receive either saline or 75, 150, or 300 [mu]g 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-[mu]g neostigmine group only (P < 0.05), and postoperative sedation was increased by neostigmine in a dose-independent fashion (P < 0.05).     

Intrathecal neostigmine with bupivacaine for infants undergoing lower abdominal and urogenital procedures: dose response

Background: Intrathecal (IT) neostigmine produces dose-dependent analgesia in adults. However, the dose of spinal neostigmine has not been investigated in infants. The purpose of this study was to assess spinal anesthesia (SA) duration provided by four doses of spinal neostigmine added to bupivacaine for lower abdominal and urogenital procedures in infants.
Methods: Seventy-five infants were randomized into five groups. The control group B received IT plain 0.5% hyperbaric bupivacaine. Groups BN.25, BN.50, BN.75, and BN1.0 received bupivacaine with 0.25, 0.5, 0.75, and 1 μg/kg of neostigmine, respectively. The primary variable was the duration of anesthesia assessed by recovery of hip flexion. Postoperative pain with facial expression, leg activity, arm activity, crying and consolability scale score,and rescue analgesic requirements were the secondary variables measured, and the side effects were noted.
Results: Seventy-three infants completed the study. There was a significant linear increase in SA duration with IT neostigmine to 65.2 (4.3) min with 0.5 μg/kg ( P <0.01), 88.2 (5.1) with 0.75 μg/kg ( P <0.001) and 92 (4.3) with 1 μg/kg ( P <0.001) from 52.4 (4.3) min with bupivacaine alone. SA duration showed no significant difference between plain bupivacaine and BN.25 ( P =0.100) or between groups BN.75 and BN1.0 ( P =0.451). Groups BN.75 and BN1.0 had significantly reduced pain scores, and the median duration before the first dose rescue analgesic was requested prolonged significantly ( P <0.001) compared with the other three groups.
Conclusions: IT neostigmine at a dose of 0.75 μg/kg added to bupivacaine significantly prolonged SA duration with reduced postoperative pain scores and rescue analgesic requirements in infants undergoing lower abdominal and urogenital procedures. No additional benefits were provided on increasing it to 1 μg/kg.     

Epidural anaesthesia as a method of pre-emptive analgesia for abdominal hysterectomy

The effect of pre- versus postincisional epidural blockade without the use of systemic opioids was investigated in a randomised, double-blind study of two groups of 25 patients undergoing abdominal hysterectomy performed under general anaesthesia. The first group received, via a lumbar epidural catheter, 0.9% saline (16 ml) 15 min prior to surgical incision and 0.5% bupivacaine (15 ml) and fentanyl 50 μg (1 ml) 15 min prior to skin closure. The second group of 25 patients received the same amount of bupivacaine and fentanyl 15 min pre-incision and saline prior to skin closure. Visual analogue pain scores and patient-controlled morphine consumption were measured at specified times for 48 h. We were unable to detect any significant difference in either of the outcome measures for the two groups and thus were unable to demonstrate that epidural blockade using local anaesthetic and opioid has a pre-emptive effect.     

Effects of Intrathecal Neostigmine, Bupivacaine, and Their Combination on Sympathetic Nerve Activity in Rats

Background: Intrathecal injection of local anesthetic agents is associated frequently with hypotension. Conversely, intrathecal administration of neostigmine increases blood pressure by enhancing the accumulation of acetylcholine in the spinal cord. The current study examined directly the interaction of intrathecal injection of bupivacaine and neostigmine on splanchnic sympathetic efferent nerve activity.

Methods: Experiments were performed in rats with intrathecal catheters implanted for the long-term. Rats were anesthetized with ketamine (40 mg/kg, intramuscularly) and alpha-chloralose (60 mg/kg, intraperitoneally). The skin incision sites were infiltrated with 1% lidocaine. Sympathetic efferent activity was recorded from the left greater splanchnic nerve. Sympathetic nerve activity was measured continuously before and after intrathecal injection of saline, 430 nmol (140 micro gram) of bupivacaine, 25 nmol (7.6 micro gram) of neostigmine, and a combination of bupivacaine and neostigmine all in volumes of 5 micro liter. Each group consisted of six animals.

Results: Compared with baseline nerve activity, intrathecal injection of neostigmine increased splanchnic sympathetic nerve activity significantly by (mean +/- SEM) 112 +/- 29% after an onset latency of 6.8 +/- 0.9 min. In contrast, bupivacaine decreased splanchnic nerve activity significantly (-65 +/- 13%) after a latency of 3.3 +/- 0.5 min after intrathecal administration. Similar to the effect of saline, intrathecal coadministration of bupivacaine and neostigmine did not alter the splanchnic sympathetic nerve activity significantly.     

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.     

Patient-controlled epidural analgesia reduces analgesic requirements compared to continuous epidural infusion after major abdominal surgery

PURPOSE: To compare the quality of pain relief and incidence of side effects between 24-hr postoperative continuous epidural infusion (CEI) and subsequent patient-controlled epidural analgesia (PCEA) with different analgesics after major abdominal surgery. METHODS: Twenty-eight women undergoing extended gynecological tumour surgery received postoperative CEI with 0.15 mL x kg(-1) x hr(-1) 0.2% ropivacaine (R: n = 14) or 0.125% bupivacaine plus 0.5 micro g x mL(-1) sufentanil (BS: n = 14) during 24 postoperative hours. Twenty-four hours later, postoperative pain management was switched to PCEA without background infusion and 5 mL single bolus application of R or BS every 20 min at most. Visual analogue scales (VAS; 1-100 mm) were assessed by patients at rest and on coughing after 24 hr of CEI and PCEA. Side effects, doses of local anesthetics and opioids were recorded and plasma concentrations of total and unbound ropivacaine and bupivacaine were measured. RESULTS: Patients required lower doses of each respective analgesic medication with PCEA (R: 108 +/- 30 mL; BS: 110 +/- 28 mL) than with CEI (R: 234 +/- 40; BS: 260 +/- 45; P < 0.01). Ropivacaine plasma concentrations were lower 24 hr after PCEA when compared with CEI (P < 0.01). No patient after PCEA but two after CEI (n = 4; NS) presented motor block. PCEA with R provided better postoperative pain relief than CEI (37 +/- 32 vs 59+/-27, P < 0.05). No difference in parenteral opioid rescue medication between CEI and PCEA was seen. CONCLUSION: PCEA in comparison to preceding CEI provides equivalent analgesia with lower local anesthetic doses and plasma levels, and without motor blocking side effects, irrespective of the applied drug regimen.     

Comparison of ropivacaine 0.1%-fentanyl and bupivacaine 0.125% — fentanyl infusions for epidural labour analgesia

PURPOSE: To compare analgesic efficacies of ropivacaine-fentanyl and bupivacaine-fentanyl infusions for labour epidural analgesia. METHODS: In this double- blind, randomized study 100, term, nulliparous women were enrolled. Lumbar epidural analgesia (LEA) was started at cervical dilatation < 5 cm using either bupivacaine 0.25% followed by bupivacaine 0.125% + 2 microg x ml(-1) fentanyl infusion (n=50) or ropivacaine 0.2% followed by ropivacaine 0.1% + 2 microg x ml(-1) fentanyl infusion (n=50). Every hour maternal vital signs, visual analog scale (VAS) pain score, sensory levels, and motor block (Bromage score) were assessed. Data were expressed as mean +/-1 SD and analyzed using Chi -Squared and Mann-Whitney U tests at <0.05. RESULTS: The onset times were 10.62+/-4.9 and 11.3+/-4.7 min for the bupivacaine and ropivacaine groups respectively (P = NS). The median VAS scores were not different between the groups at any of the evaluation periods. However, at least 80% of patients in the ropivacaine group had no demonstrable motor block after the first hour compared with only 55% of patients given bupivacaine (P =0.01). CONCLUSIONS: Both bupivacaine and ropivacaine produce satisfactory labour analgesia. However, ropivacaine infusion is associated with less motor block throughout the first stage of labour and at 10 cm dilatation.     

The analgesic efficacy of patient-controlled bupivacaine wound instillation after total abdominal hysterectomy with bilateral salpingo-oophorectomy

To assess the effect of local anesthetic wound instillation on visceral and somatic pain, we studied 36 patients undergoing total abdominal hysterectomy and bilateral salpingo-oophorectomy. A standard general anesthetic was administered. On completion of the operation, a multiorifice 20-gauge epidural catheter was placed above the superficial abdominal fascia such that the tip was at the midpoint of the surgical wound. After surgery, either bupivacaine 0.25% (Bupivacaine group) or sterile water (Control group) was administered via a patient-controlled analgesia device programmed to deliver 9.0 mL with a 60-min lockout interval. During the first 6 h after surgery, rescue IV morphine (2 mg) was administered every 10 min until a visual analog scale score of <30 mm was achieved. Thereafter, on patient request, rescue meperidine 1 mg/kg IM was administered. When compared with the Control group, significantly (P < 0.001) less rescue analgesia was administered to patients in the Bupivacaine group. Rescue morphine administered during the first 6 h after surgery was 6 +/- 4 mg versus 12 +/- 6 mg (P < 0.001) for the Bupivacaine and Control groups, respectively. Rescue meperidine administered was 29 +/- 37 mg versus 95 +/- 36 mg (P < 0.001) for the Bupivacaine and Control groups, respectively. Nausea and antiemetic drug administration was significantly (P = 0.003) less in the Bupivacaine group. Pain scores were similar between the groups. Patient satisfaction was significantly (P = 0.04) more in the Bupivacaine group. We conclude that bupivacaine wound instillation decreases opioid requirements and nausea in the first 24 h after total abdominal hysterectomy with bilateral salpingo-oophorectomy. IMPLICATIONS: Bupivacaine instillation via an electronic patient-controlled analgesia device provides effective analgesia after total abdominal hysterectomy with bilateral salpingo-oophorectomy.     

Intraoperative intravenous ketamine in combination with epidural analgesia: postoperative analgesia after renal surgery

We designed this double-blinded, randomized, controlled study to evaluate the effect of small-dose ketamine IV in combination with epidural morphine and bupivacaine on postoperative pain after renal surgery. An epidural catheter was inserted, and the administration of morphine and bupivacaine was started before surgery. Forty patients were assigned to one of two groups (ketamine or control). The ketamine group was administered a ketamine bolus and infusion during surgery. The median visual analog pain scale (VAS) scores at rest were significantly lower in the ketamine group during the first 6 h (P < 0.01). VAS pain scores on coughing were also significantly lower in the ketamine group (P < 0.01). Cumulative postoperative total analgesic consumption was less in the ketamine group on Days 1 and 2 (P < 0.001). The first analgesic demand time was shorter in the control group (9.2 +/- 11.5 min) than in the ketamine group (22.3 +/- 17.1 min) (P < 0.0001). The incidence of nausea and pruritus was more frequent in the control group (P < 0.05). In conclusion, postoperative analgesia was more effective when spinal cord and brain sensitization were blocked by a combination of epidural morphine/bupivacaine and IV ketamine. IMPLICATIONS: Renal nociception conducted multisegmentally by both the spinal nerves (T10 to L1) and the vagus nerve cannot be blocked by epidural analgesia alone. We demonstrated that IV ketamine had an improved analgesic or opioid-sparing effect when it was combined with epidural bupivacaine and morphine after renal surgery.