Comparison of clonidine, morphine or placebo mixed with bupivacaine during continuous spinal anaesthesia

Purpose

To compare intraoperative anaesthetic and haemodynamic effects of clonidine-bupivacaine, morphine-bupivacaine and placebo-bupivacaine combinations during continuous spinal anaesthesia.

Methods

Thirty six geriatric patients, undergoing knee replacement using continuous spinal anaesthesia were randomly assigned to: Placebo (n = 12), clonidine (n = 12) and morphine (n = 12), where I ml saline, 0.15 mg clonidine or 0.15 mg morphine were mixed with 10 mg bupivacaine 0.5%. Anaesthetic variables studied were maximal sensory level and degree of motor block, duration of surgical analgesia and duration of anaesthesia. Changes in systolic arterial pressure and vasopressor requirements were evaluated.

Results

Maximal sensory level and degree of motor block were comparable among the groups. Before surgery two patients in the placebo group, three in the donidine and one in the morphine group received one additional ml bupivacaine 0.5% because of inadequate anaesthesia and were not considered for determination of duration of surgical analgesia. In the remainder, 1/9 in the donidine group, 8/10 in placebo and 8/11 in morphine (P < 0.05) received reinjection of bupivacaine for surgical pain. These injections were given about 2 1/2 hr after the initial intrathecal injection, the duration of anaesthesia being about four hours. During the first 30 min after the initial injection the decrease in systolic pressure was greater in the donidine and morphine than in the placebo group (P < 0.05).Thereafter, vasopressor requirements were higher only in the donidine group (P < 0.05).

Conclusion

In elderly patients 0.15 mg donidine but not 0.15 mg morphine prolonged surgical analgesia when added to 10 mg plain bupivacaine.     

Postoperative analgesia for outpatient arthroscopic knee surgery with intraarticular clonidine and/or morphine

Both clonidine, an alpha(2) agonist, and morphine, an opioid agonist, provide enhanced patient analgesia after arthroscopic knee surgery when administered via the intraarticular (IA) route. Clonidine potentiates morphine analgesia in the animal model. We designed this study to determine whether clonidine or morphine results in better analgesia and whether their combination would provide superior analgesia to either drug alone. We evaluated 60 patients undergoing arthroscopic knee meniscus repair under local anesthesia with sedation. After surgery, patients were randomized into four IA groups: Group B received 30 mL 0.25% bupivacaine; Group BC received 30 mL 0.25% bupivacaine and clonidine 1 microg/kg; Group BM received 30 mL 0.25% bupivacaine and morphine 3 mg; and Group BCM received 30 mL 0.25% bupivacaine, clonidine 1 microg/kg, and morphine 3 mg. This study revealed a significant benefit from the individual IA administration of both clonidine and morphine. The combination of these drugs resulted in decreased postoperative pain and analgesic use, as well as an increased analgesic duration compared with either drug alone. We conclude that IA clonidine and morphine improved comfort compared with either drug alone in patients undergoing knee arthroscopy.     

Comparison of morphine alone with morphine plus clonidine for postoperative patient-controlled analgesia

Background. Clonidine is an     

Comparison of morphine alone with morphine plus clonidine for postoperative patient-controlled analgesia

Editor—We were interested to read the article by Jeffsand colleagues¹ on the addition of clonidine to morphine PCAdevices, and would like to make some comments. First, the medianpain score in the morphine group for the first 12 h wasgiven as 3 with a range of 1–4, although it was stated     

Intraoperative clonidine enhances postoperative morphine patient-controlled analgesia

In this prospective study, the postoperative analgesic effects of intraoperative iv clonidine were evaluated. Two hundred consecutive patients undergoing major abdominal surgery were randomly assigned to either balanced anaesthesia with iv clonidine (Group 1) or balanced anaesthesia alone (Group 2). A PCA infuser was connected immediately after tracheal extubation. It was programmed to deliver morphine "on demand" iv boluses at doses of 1 mg for patients greater than 65 yr and 1.5 mg for women or 2 mg for men less than 65 yr old. A blinded observer assessed postoperative analgesia by recording the analgesic demands (both met and unmet), patient pain scores, sedation scores, and any side effects during the first 36 hr after surgery. Intraoperative clonidine reduced the number of analgesic demands during the observation period (45 +/- 27 demands in Group 1 vs 81 +/- 60 in Group 2, P = 0.0001). This resulted in a reduction in morphine delivered (55.4 +/- 30.6 mg vs 67.1 +/- 45.1 mg, P less than 0.05), mainly during the first 12 hr (19.7 +/- 11.1 mg vs 27.6 +/- 18.1, mg P less than 0.001) and the unmet demand rate was also reduced at all time intervals (P less than 0.01). Clonidine did not exacerbate sedation or side effects. However, clonidine provided better analgesia in men and in patients less than 65 yr of age. Intraoperative iv clonidine enhances morphine analgesia after abdominal surgery.     

Intra-articular morphine and clonidine produce comparable analgesia but the combination is not more effective

Both intra-articular morphine and clonidine produce analgesia. This study was designed to compare the analgesic effects of the two drugs, used separately and in combination. We studied 90 patients undergoing arthroscopy of the knee under general anaesthesia. Patients were allocated randomly to receive 20 ml of intra-articular isotonic saline solution containing morphine 2 mg, clonidine 150 micrograms or both. Pain was assessed on an visual analogue scale after operation and time for rescue medication was measured. There was no difference in VAS scores between the three groups and the time for rescue analgesic was comparable. We conclude that intra-articular morphine and clonidine have comparable analgesic effects in the doses used. The combination of both drugs did not seem to increase analgesia.      

Fast-track coronary artery bypass grafting surgery under general anesthesia with remifentanil and spinal analgesia with morphine and clonidine

OBJECTIVE: Effective postoperative analgesia is a critical part of fast-track cardiac surgery. This study compared the postoperative analgesic effect of fast-track anesthesia with remifentanil and spinal morphine and clonidine with that of sufentanil anesthesia followed by patient-controlled administration of intravenous morphine. DESIGN: Prospective, blinded, randomized study. SETTING: Single private institution. PARTICIPANTS: Forty patients selected for coronary artery bypass graft surgery allocated randomly into 2 groups. INTERVENTIONS: General anesthesia was performed with etomidate, isoflurane, cisatracurium, and either remifentanil (0.10-0.25 microg/kg/min) or sufentanil (up to 3.5 microg/kg). In the remifentanil group, patients received spinal morphine (4 microg/kg) and clonidine (1 microg/kg) before induction. Postoperatively, patients in both groups were connected to an intravenous patient-controlled analgesia (PCA) morphine pump that delivered a 1-g bolus with a 7-minute lockout interval. MEASUREMENTS AND MAIN RESULTS: Patients were evaluated for pain on a visual analog scale (VAS), at rest and on deep breathing, and for intravenous PCA morphine consumption during 24 hours. The intravenous PCA morphine 24-hour cumulative dose was lower in the fast-track than in the control group (15.8+/-12.6 v 32.7+/-22.3 mg, p<0.05). Before extubation, VAS scores were higher in the fast-track group, but after they were lower both at rest and during deep breathing. Extubation delay was shorter in the fast-track group (156.5+/-46.1 v 272+/-116.4 minutes, p<0.05). CONCLUSION: The combination of anesthesia with remifentanil and spinal analgesia with morphine and clonidine produces effective analgesia after coronary artery surgery and a rapid extubation time.     

The antinociceptive effect of the combination of spinal morphine with systemic morphine or buprenorphine.

We sought to analyze the mode of interaction of spinal morphine with systemic morphine or buprenorphine, administered in a wide range of antinociceptive doses. The study was performed on Sprague-Dawley rats by using a plantar stimulation test and isobolographic and fractional analyses of drug interaction. The isobolographic and fractional analyses demonstrated that intrathecal morphine interacted with subcutaneous morphine in a synergistic manner while producing a 50% or 75% antinociceptive effect. The sum of D(75) fractions was more than that for 50% antinociception, suggesting a less dramatic interaction. The combination with a maximal relative dose of systemic morphine (0.66:1) showed a maximal degree of supraadditivity. The interaction between spinal morphine and systemic buprenorphine was similar to that of morphine/morphine, although the supra-additivity was not as pronounced. For the doses that produced a 50% antinociceptive effect, a synergistic interaction was observed only for the combination with a morphine/buprenorphine ratio of 1.33:1. When the relative amount of intrathecal morphine was decreased or increased, the effect became additive. At the doses that produced 75% antinociception, both combinations of morphine and buprenorphine demonstrated supraadditive interaction. Implications: Spinal morphine interacts with systemic morphine or buprenorphine in asupraadditive manner. This mode of interaction most probably results from the simultaneous activation of spinal and supraspinal antinociceptive systems.Supraspinal structures played a more important role in the antinociceptive effect of experimental combinations than structures of the spinal cord.     

Pre-emptive analgesia with epidural morphine or morphine and bupivacaine

Studies of preemptive analgesia in humans have shown conflicting results. The study design, patient population and the duration of assessment of postoperative pain are important in the evaluation of preemptive analgesia. We carried out a prospective, randomized, double-blind controlled study in 80 patients of physical status ASA 1-3 undergoing upper abdominal and thoracic surgery. Patients received two epidural injections, one 20 minutes before induction and the other at the end of surgery. Study solution was either morphine (50 micrograms/kg), with or without 0.1% bupivacaine in 10 ml of normal saline, or normal saline alone. The study groups (Pre M, Pre MB) were given either morphine or morphine-bupivacaine before induction and saline at the end of surgery. The control groups (Post M, Post MB) were given saline before induction and morphine or morphine-bupivacaine at the end of surgery. Postoperative pain was assessed with a Visual Analogue Scale (VAS) during coughing and deep breathing at six-hourly intervals for five days. Epidural morphine was given if the VAS exceeded 4. Pre MB compared to Post MB had a significantly increased interval between the analgesic top-ups (P < 0.01) and decreased total postoperative morphine requirements (P < 0.0001) and number of top-ups (P < 0.001). Pre M and Post M were comparable. Pre MB compared to Pre M had significantly decreased total postoperative morphine requirements (P < 0.0001) and number of top-ups (P < 0.0001). Epidural morphine plus bupivacaine is effective as a preemptive analgesic. Morphine plus bupivacaine has better efficacy than morphine given alone before the induction of anaesthesia.     

Oral clonidine premedication enhances postoperative analgesia by epidural morphine

This study was designed to evaluate the effects of oral clonidine premedication on postoperative analgesia by epidural morphine in a prospective, randomized, double-blinded design. Sixty consenting patients, scheduled for total abdominal hysterectomy, were randomly assigned to one of three groups (n = 20 each); the clonidine-morphine group received oral clonidine 5 microg/kg 90 min before arriving in the operating room and epidural morphine 2 mg before induction of general anesthesia, the clonidine-placebo group received oral clonidine 5 microg/kg and no epidural morphine, and the placebo-morphine group received no clonidine and epidural morphine 2 mg. An epidural catheter was placed at the L1-2 or L2-3 interspace, and 1.5% lidocaine was used for surgical anesthesia in all patients. General anesthesia was then induced with propofol, and maintained with a continuous infusion of propofol and 67% nitrous oxide in oxygen during surgery. Four patients were subsequently withdrawn from the study. After surgery, patient-controlled analgesia using IV morphine was used to assess analgesic requirement. Morphine consumptions determined every 6 h after surgery in the clonidine-morphine and placebo-morphine groups were significantly less than the clonidine-placebo group until 12 h after surgery, whereas those of the clonidine-morphine group were significantly less than the placebo-morphine group from 13 to 42 h after surgery. Visual analog (pain) scale (VAS) scores in the clonidine-morphine group were significantly lower than the placebo-morphine group at 48 h at rest, and at 1, 24, 36, and 48 h with movement. Similarly, VAS scores in the clonidine-morphine group were significantly lower than the clonidine-placebo group at 1 and 6 h both at rest and with movement, whereas VAS scores in the clonidine-placebo group were significantly lower than the placebo-morphine group at 24, 36, and 48 h at rest and with movement. The incidence of nausea and pruritus was similar between groups. We conclude that the combination of oral clonidine and epidural morphine produces more potent and longer lasting postoperative analgesia than either drug alone without increasing the incidence of adverse effects after major gynecologic surgeries. IMPLICATIONS: A small dose of epidural morphine is often used for postoperative analgesia. We found that oral clonidine premedication 5 microg/kg improves the analgesic efficacy of epidural morphine without increasing the incidence of adverse side effects.     

Neostigmine combined with bupivacaine, clonidine, and sufentanil for spinal labor analgesia.

We previously found that spinal clonidine prolongs labor analgesia when combined with spinal bupivacaine and sufentanil. We sought to determine whether the addition of spinal neostigmine to these drugs would further enhance labor analgesia. By use of a combined spinal/epidural technique, 36 patients were randomized to receive a hyperbaric spinal injection of bupivacaine 2.5 mg plus clonidine 50 microg and sufentanil 10 microg with or without neostigmine 10 microg. Pain, maternal hemodynamics, fetal heart rate, nausea, pruritus, sedation, motor block, sensory levels to pinprick, and maternal oxygen saturation were assessed at regularly specified intervals after spinal injection until additional analgesia was requested. The duration of spinal analgesia was similar between groups (215 +/- 60 min in the Control group versus 205 +/- 62 min in the Neostigmine group). Likewise, pain scores, the duration of labor, Apgar scores, and side effects were similar between groups except that patients administered neostigmine experienced significantly more nausea and vomiting (53% vs 7%, P = 0.01). We conclude that spinal neostigmine 10 microg produces severe nausea and does not potentiate the duration of spinal analgesia in laboring women from spinal bupivacaine, clonidine, and sufentanil. IMPLICATIONS: Spinal neostigmine 10 microg as an adjunct to spinal bupivacaine, clonidine, and sufentanil produces severe nausea and fails to potentiate analgesia in laboring women.     

A randomized, double-blinded comparison of intrathecal morphine, sufentanil and their combination versus IV morphine patient-controlled analgesia for postthoracotomy pain

We compared the analgesic effect of lumbar intrathecal (IT) 0.5 mg morphine (Group M, n = 10), 50 microg sufentanil (Group S, n = 10), and their combination (Group S-M, n = 10) given before general anesthesia and patient-controlled analgesia with IV morphine (Group C, n = 19) in a randomized, double-blinded study performed in patients undergoing thoracotomy. Pain visual analog scale (VAS) and morphine consumption were assessed for 24 h. In Group S-M the number of patients initially titrated with IV morphine was less than in group C (30 vs 84%, P < 0.05). Morphine requirement was higher in Group C (71 +/- 30 mg) than in Groups S (46 +/- 34 mg, P < 0.05), M (38 +/- 31 mg, P < 0.05) and S-M (23 +/- 16 mg, P < 0.01). VAS scores were significantly decreased during the first 0-11 postoperative h at rest and during the first 0-8 postoperative h on coughing in Groups M and S-M rather than in Group C. The incidence of side effects was infrequent except for urinary retention. Preoperative IT morphine or combined sufentanil and morphine could be given as a booster to achieve rapidly effective analgesia in the immediate postoperative period. Implications: As compared with IV patient-controlled analgesia, intrathecal morphine or combined sufentanil and morphine provided superior postoperative pain relief both at rest (11 h) and on coughing (8 h) than did IV patient-controlled analgesia morphine alone. IV morphine requirement was decreased during the first postoperative day after posterolateral thoracotomy.     

Spinal clonidine produces less urinary retention than spinal morphine

We have conducted a double-blind, randomized study in two groups of 20 patients each, undergoing hip surgery during spinal anaesthesia, to compare the incidence of urinary retention after spinal morphine or clonidine. Patients received 0.5% spinal bupivacaine 15 mg combined with either clonidine 75 micrograms or morphine 0.2 mg. After operation, patients were examined for micturition, bladder distension, or both; when they failed to void, they received naloxone 0.2 mg, and if bladder distension persisted, a catheter was inserted. At 12 h, all patients in the morphine group but only five in the clonidine group had bladder distension, and at 24 h this was present in seven and one patient in the morphine and clonidine groups, respectively (P < 0.001). Naloxone was given in 16 and one, and a catheter was placed in one and six patients in the morphine and clonidine groups, respectively (P < 0.001). We conclude that spinal clonidine impaired bladder function to a lesser extent than morphine.      

Caudal bupivacaine supplemented with morphine or clonidine,or supplemented with morphine plus clonidine in children undergoing infra-umbilical urological and genital procedures: a prospective,randomized and double-blind study

Purpose  

We aimed to evaluate postoperative analgesia of morphine, or clonidine, or morphine plus clonidine, added to caudal bupivacaine in children undergoing infra-umbilical urological and genital procedures.     

Ketorolac and spinal morphine for postcesarean analgesia

This study was designed to compare spinal morphine (SM), ketorolac (K), and a combination of the two drugs with respect to analgesic efficacy and side effects in postcesarean patients. Forty-eight parturients having bupivacaine spinal anesthesia for cesarean delivery randomly received in a double-blind manner either: SM: 0.1 mg or SM: 0.2 mg (but no K); SM: 0.1 mg plus K 60 mg intravenously (i.v.) one hour after spinal injection, and 30 mg i.v. every 6 h for three doses or i.v. K dosed as previously described (but no SM). Analgesia and side effects were evaluated during the first 20 h. Forty-eight women were studied. There were no significant differences in analgesia among the groups, although patients receiving SM: 0.1 mg tended to have less satisfactory intraoperative analgesia. Pruritus was common in all patients receiving SM whereas patients who received K had the lowest overall scores for severity of side effects. No serious complications occurred and all groups expressed similarly high satisfaction at the 24 h visit. We conclude that there is no advantage to combining SM and K, and that K provides satisfactory postcesarean analgesia with few side effects.     

大鼠脊髓株网膜下腔吗啡耐药时可乐定的镇痛效应

目的 研究大鼠脊髓部位吗啡耐药时可乐定的镇痛效应。方法 大鼠蛛网膜下腔埋管,以甩尾法测痛,建立大鼠蛛网膜下腔吗啡耐药动物模型。大鼠耐药后蛛网膜下腔分别注射吗啡和可乐定测痛。结果 蛛网膜下腔注吗啡１５ｕｇ,镇痛效应百分比（％ＭＰＥ）由耐药前的８２．４％下降到耐药后的１８．６％（Ｐ〈０．０１）;蛛网膜下腔注可乐定４０ｕｇ,％ＭＰＥ在耐药前为４６．５％,耐药后为４８．１％（Ｐ〉０．０５）。结论 脊髓部位产生吗啡耐药后,蛛网膜下腔注吗啡的镇痛作用显著减弱,但对可乐定的镇痛作用无明显影响。