Anesthesia and analgesia
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Anesthesia and analgesia · Jul 2000
Randomized Controlled Trial Clinical TrialGabapentin enhances the analgesic effect of morphine in healthy volunteers.
The most effective group of drugs for the treatment of severe pain is opioid analgesics. Their use, however, is limited by decreased effects in neuropathic and chronic pain as a result of increased pain and development of tolerance. Gabapentin (GBP) is effective in both experimental models of chronic pain and clinical studies of neuropathic pain. Therefore, we investigated, in a randomized, placebo-controlled, double-blinded study, the pharmacodynamic and pharmacokinetic interaction of GBP and morphine in 12 healthy male volunteers. Morphine (60 mg, controlled release) or placebo was administered at 8:00 AM, and GBP (600 mg) or placebo was administered at 10:00 AM, thus comparing the analgesic effect of placebo + GBP (600 mg) with placebo + placebo and morphine (60 mg) + GBP in comparison to morphine plus placebo by using the cold pressor test. The duration and intensity of the side effects were assessed by using visual analog scales. The analgesic effect was evaluated by the change in the area under the curve (h x %; 0% baseline before Medication 1) of pain tolerance. Placebo + GBP (18.9% x h, 95% confidence interval [CI]: -2.5 to 40.3) did not present any significant analgesic effect compared with placebo + placebo (4.7% x h, 95% CI: -16.7 to 26.1). A significant increase in pain tolerance was observed comparing the combination of morphine and GBP (75.5% x h, 95% CI: 54.0-96.9) with morphine + placebo (40.6% x h, 95% CI: 19. 2-62.0). The observed adverse events after placebo + GBP were not significantly different compared with placebo + placebo. Morphine + placebo led to the expected opioid-mediated side effects. They were significantly more pronounced compared with placebo + placebo but did not differ significantly compared with the combination of morphine + GBP. Concerning the pharmacokinetic variables of morphine and its glucuronides, no significant difference between morphine + placebo and morphine + GBP was observed, whereas the area under the curve of GBP (43.9 +/- 5.3 vs 63.4 +/- 16.2 microg. h(-1). mL(-1), P < 0.05) significantly increased, and apparent oral clearance (230.8 +/- 29.4 mL/min vs 178 +/- 97.9 mL/min, P = 0.06) and apparent renal clearance (86.9 +/- 20.6 vs 73.0 +/- 24.2 mL/min, P = 0.067) of GBP decreased when morphine was administered concomitantly. These results suggest two different sites for the pharmacokinetic interaction-one at the level of absorption and the other at the level of elimination. Our study reveals both a pharmacodynamic and pharmacokinetic interaction between morphine and GBP, leading to an increased analgesic effect of morphine + GBP. These results and the good tolerability of GBP should favor clinical trials investigating the clinical relevance of the combination of morphine and GBP for treating severe pain. ⋯ In a randomized, placebo-controlled, double-blinded trial with 12 healthy volunteers, we studied the interaction of morphine and gabapentin using the cold pressor test. The anticonvulsant gabapentin enhanced the acute analgesic effect of morphine. Furthermore, the plasma concentration of gabapentin was increased when morphine was administered concomitantly. Therefore, the well tolerated combination of gabapentin and morphine may improve pain therapy, especially in pain states, like chronic and neuropathic pain, which respond poorly to opioids.
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Anesthesia and analgesia · Jul 2000
Randomized Controlled Trial Clinical TrialThe effect of timing of dexamethasone administration on its efficacy as a prophylactic antiemetic for postoperative nausea and vomiting.
We evaluated the timing effect of a 10-mg IV administration of dexamethasone on its efficacy as a prophylactic antiemetic on postoperative nausea and vomiting (PONV). One hundred twenty women (n = 40 in each of three groups) undergoing abdominal total hysterectomy under general anesthesia were enrolled in this randomized, double-blinded, placebo-controlled study. Group 1 received dexamethasone before the induction of anesthesia, Group 2 received dexamethasone at the end of anesthesia, and Group 3 received placebo (saline). The incidence of PONV was evaluated. During the postoperative period of 0-2 h, patients in Group 1 reported a less frequent incidence of PONV (15%) than those in Groups 2 and 3 (45% and 53%, respectively). Patients in Group 1 also requested less rescue antiemetic (8%) than those in Groups 2 and 3 (30% and 35%, respectively). During the postoperative period of 2-24 h, patients in both Groups 1 and 2 reported less frequent incidences of PONV (25% and 28%) and requested fewer rescue antiemetics (13% and 15%) than those in Group 3 (55% and 38%, respectively). In conclusion, the prophylactic IV administration of dexamethasone immediately before the induction, rather than at the end of anesthesia, was more effective in preventing PONV. ⋯ We evaluated the effect of timing of dexamethasone administration on its efficacy as a prophylactic antiemetic on postoperative nausea and vomiting. We found that dexamethasone, when given immediately before the induction of anesthesia, was more effective than when given at the end of anesthesia.
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Anesthesia and analgesia · Jul 2000
Randomized Controlled Trial Comparative Study Clinical TrialThe recovery of cognitive function after remifentanil-nitrous oxide anesthesia is faster than after an isoflurane-nitrous oxide-fentanyl combination in elderly patients.
We tested the hypothesis that remifentanil-nitrous oxide (N(2)O) anesthesia shortens postoperative emergence and recovery compared with an isoflurane-N(2)O-fentanyl combination in elderly patients undergoing spinal surgery. A total of 60 patients (>65 yr old) were randomly assigned to one of two groups for maintenance of anesthesia. After the induction with 3.6 +/- 1.2 mg/kg IV thiopental and endotracheal intubation facilitated with 1.4 +/- 0.5 mg/kg succinylcholine, patients were maintained with either 0.5%-1.5% isoflurane, 70% N(2)O, and up to 7 microg/kg fentanyl (iso/fent group) or 48 +/- 11 microg/kg remifentanil and 70% N(2)O (remi group). A mini-mental status examination was used to assess cognitive ability preoperatively, at 15, 30, and 60 min after arrival at the postanesthesia care unit and again 12-24 h postoperatively. The time from the conclusion of anesthesia to spontaneous respiration was similar in both groups. Times to eye opening (4.8 +/- 2.6 vs 2.3 +/- 1.1 min), extubation (6.8 +/- 3.8 vs 3.2 +/- 2.1 min), and verbalization (9.9 +/- 6.2 vs 3.9 +/- 2.6 min) were significantly shorter for the remi group (P < 0.05). Postoperative mini-mental status examination scores were significantly lower in the iso/fent group at 15 (16.3 +/- 5.8 vs 23. 7 +/- 3.3), 30 (20.2 +/- 5.2 vs 26.3 +/- 2.7), and 60 min (23.5 +/- 4.4 vs 27.5 +/- 2.0) (P < 0.001); however, the scores equalized after 12 h. Requirements for postoperative analgesics were similar in the two groups. More patients in the remi group were treated with antiemetics (21 vs 7, P = 0.06). Use of remifentanil-N(2)O for maintenance did not shorten the overall length of stay in the postanesthesia care unit; a stay is often related to multiple administrative issues, rather than cognitive recovery. ⋯ Maintenance of anesthesia with remifentanil-nitrous oxide (N(2)O), compared with isoflurane-N(2)O-fentanyl, can safely shorten postoperative recovery of cognitive function in a geriatric population. Earlier recovery may facilitate postoperative neurological assessment. Use of remifentanil-N(2)O for maintenance did not shorten the overall length of stay in the postanesthesia care unit, a stay often related to multiple administrative issues, rather than cognitive recovery.
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Anesthesia and analgesia · Jul 2000
Randomized Controlled Trial Comparative Study Clinical TrialCaruncle single injection episcleral (Sub-tenon) anesthesia for cataract surgery: mepivacaine versus a lidocaine-bupivacaine mixture.
We compared the quality of anesthesia provided by mepivacaine 2% or a mixture of lidocaine 2%-bupivacaine 0.5%, both with hyaluronidase, in caruncle single-injection episcleral (sub-Tenon) anesthesia. Sixty patients undergoing cataract surgery were included in this randomized, double-blinded study. The time to the onset of blockade, maximal akinesia, need for supplemental injection, and time to recovery were recorded. With mepivacaine, the time to onset was slightly shorter, and the akinesia score higher, than with the mixture. Although statistically significant, these differences are small. With mepivacaine, the time to recovery was shorter. We conclude that the reproducible short duration of the block may be an advantage in outpatient surgery. ⋯ We compared the classic mixture of lidocaine 2% plus bupivacaine 0.5% to mepivacaine 2% for caruncle episcleral (sub-Tenon) anesthesia for cataract surgery. Mepivacaine provided a more efficient block with a quicker onset and a quicker recovery. However, these differences were very small and were of little clinical interest.
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Anesthesia and analgesia · Jul 2000
Randomized Controlled Trial Comparative Study Clinical TrialExtended "three-in-one" block after total knee arthroplasty: continuous versus patient-controlled techniques.
This prospective, randomized, double-blinded study assessed the efficacy of patient-controlled analgesia (PCA) techniques for extended "3-in-1" block after total knee arthroplasty. A total of 45 patients were divided into three groups of 15. Over 48 h, all patients received 0.125% bupivacaine with 1 microg/mL clonidine via a femoral nerve sheath catheter in the following manner: as a continuous infusion at 10 mL/h in Group 1; as a continuous infusion at 5 mL/h plus PCA boluses (2.5 mL/30 min) in Group 2; or as PCA boluses only (10 mL/60 min) in Group 3. Pain scores, sensory block, supplemental analgesia, bupivacaine consumption, side effects, and satisfaction scores were recorded. Pain scores and supplemental analgesia were comparable in the three groups. Bupivacaine consumption was significantly less in Groups 2 and 3 than in Group 1 (P < 0.01), and in Group 3 than in Group 2 (P < 0.01). Side effects and satisfaction were comparable in the three groups. We conclude that extended "3-in-1" block provides efficient pain relief after total knee arthroplasty and that, compared with a continuous infusion, PCA techniques reduce the local anesthetic consumption without compromise in patient satisfaction or visual analog scale scores. Of the two PCA techniques tested, PCA boluses (10-mL lockout; time, 60 min) of 0.125% bupivacaine with 1 microg/mL clonidine was associated with the smallest local anesthetic consumption, and is, therefore, the recommended extended "3-in-1" block technique. ⋯ We demonstrated that, after total knee arthroplasty, an extended "3-in-1" block consisting of patient-controlled analgesia boluses (10 mL/60 min) of 0.125% bupivacaine with 1 microg/mL clonidine provides efficient postoperative analgesia and significantly minimizes local anesthetic consumption.