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 Comparative Study Clinical TrialFast-tracking after immersion lithotripsy: general anesthesia versus monitored anesthesia care.
Both monitored anesthesia care (MAC) and general anesthesia (GA) offer advantages over epidural anesthesia for immersion lithotripsy. We compared propofol-based MAC and desflurane-based GA techniques for outpatient lithotripsy. After receiving midazolam 2 mg IV, 100 subjects were randomly assigned to one of two anesthetic treatment groups. In the MAC group, propofol 50-100 microg. kg(-1). min(-1) IV was titrated to maintain an observer's assessment of alertness/sedation score of 2-3 (5 = awake/alert to 1 = asleep). Remifentanil 0.05 microg.kg(-1). min(-1) IV supplemented with 0.125 microg/kg IV boluses, was administered for pain control. In the GA group, anesthesia was induced with propofol 1.5 mg/kg IV and remifentanil 0.125 microg/kg IV and maintained with desflurane (2%-4% inspired) and nitrous oxide (60%). Tachypnea (respiratory rate >20 breaths/min) was treated with remifentanil 0.125 microg/kg IV boluses. In the GA group, droperidol (0.625 mg IV) was administered as a prophylactic antiemetic. Recovery times and postoperative side effects were assessed up to 24 h after the procedure. Compared with MAC, the use of GA reduced the opioid requirement and decreased movements and episodes of desaturation (<90%) during the procedure. Although the GA group took longer to return to an observer's assessment of alertness/sedation score of 5, discharge times were similar in both groups. We conclude that GA can provide better conditions for outpatient immersion lithotripsy than MAC sedation without delaying discharge. ⋯ A desflurane-based general anesthetic technique using the cuffed oropharyngeal airway device was found to be a highly acceptable alternative to propofol-based monitored anesthesia care sedation for outpatient immersion lithotripsy.
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Anesthesia and analgesia · Jul 2000
Randomized Controlled Trial Clinical TrialThe effects of the single or multiple injection technique on the onset time of femoral nerve blocks with 0.75% ropivacaine.
We evaluated the effect of the injection technique on the onset time and efficacy of femoral nerve block performed with 0.75% ropivacaine. A total of 30 patients undergoing arthroscopic knee surgery were randomly allocated to receive femoral nerve blockade with 0.75% ropivacaine by using either a single injection (Single group, n = 15) or multiple injection (Multiple group, n = 15). Nerve blocks were placed by using a short-beveled, Teflon-coated, stimulating needle. The stimulation frequency was set at 2 Hz, and the intensity of stimulating current, initially set at 1 mA, was gradually decreased to <0.5 mA after each muscular twitch was observed. In the Single group, 12 mL of 0.75% ropivacaine was slowly injected, as soon as the first muscular twitch was observed. In the Multiple group, the stimulating needle was inserted and redirected, eliciting each of the following muscular twitches: contraction of vastus medialis, vastus intermedius, and vastus lateralis. At each muscular twitch, 4 mL of the study solution was injected. Placing the block required 4.2 +/- 1.7 min (median, 5 min; range, 2-8 min) in the Multiple group and 3.4 +/- 2.2 min (median, 3 min; range, 1-5 min) in the Single group (P = 0.02). Onset of nerve block (complete loss of pinprick sensation in the femoral nerve distribution with concomitant inability to elevate the leg from the operating table with the hip flexed) required 10 +/- 3.7 min in the Multiple group (median, 10 min; range, 5-20 min) and 30 +/- 11 min in the Single group (median, 30 min; range, 10-50 min) (P < 0.0005). Propofol sedation was never required to complete surgery; although 0.1 mg fentanyl at trocar insertion was required in two patients of the Multiple group (13%) and nine patients of the Single group (60%) (P = 0.02). We conclude that searching for multiple muscular twitches shortened the onset time and improved the quality of femoral nerve block performed with small volumes of 0.75% ropivacaine. ⋯ This prospective, randomized, blinded study was conducted to evaluate the effect of searching for multiple muscular twitches when performing femoral nerve block with small volumes of 0. 75% ropivacaine. Our results demonstrated that multiple injections markedly shortened the onset time and improved the quality of nerve blockade. This technique-related effect must be carefully considered when different clinical studies evaluating the use of new local anesthetic solutions for peripheral nerve blocks are compared.
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Anesthesia and analgesia · Jul 2000
Randomized Controlled Trial Clinical TrialKetorolac suppresses postoperative bladder spasms after pediatric ureteral reimplantation.
We evaluated the efficacy of ketorolac in suppressing postoperative bladder spasms after ureteroneocystostomy (ureteral reimplantation). Twenty-four pediatric patients undergoing intravesical ureteroneocystostomy were enrolled prospectively to receive either ketorolac or placebo via double-blinded randomization. Twelve patients in each group shared similar preoperative characteristics. All were maintained on an epidural infusion of bupivacaine (0.1%) with fentanyl (2 microg/mL) throughout the study. Patients were given either ketorolac (0.5 mg. kg(-1). dose(-1)) or placebo (equivalent volume saline) IV after surgery and every 6 h thereafter for 48 h. Parents were instructed to record bladder spasm episodes prospectively by using a standardized time-flow diary. Three patients (25%) in the ketorolac group experienced bladder spasms, compared with 10 patients (83%) in the placebo group (two-sided P < 0.05). The median severity score for the ketorolac group was 1.2 (mild = 1.0, severe = 3.0), compared with 2.6 for the placebo group (P = 0.003). We conclude that IV ketorolac reduces the frequency and severity of postoperative bladder spasms after intravesical ureteroneocystostomy. ⋯ We studied the efficacy of ketorolac, a prostaglandin synthesis inhibitor, in the treatment of bladder spasm after ureteroneocystostomy (antireflux operation). Patients were randomized in a double-blinded manner to receive either ketorolac or placebo after the surgery. We demonstrate that ketorolac reduces the frequency and severity of postoperative bladder spasm.
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Anesthesia and analgesia · Jul 2000
Randomized Controlled Trial Clinical TrialProphylactic intravenous ondansetron reduces the incidence of intrathecal morphine-induced pruritus in patients undergoing cesarean delivery.
Pruritus is a common side effect of intrathecal morphine injection for postoperative pain control. Its incidence is especially high in patients undergoing cesarean delivery. We investigated the effectiveness of ondansetron in preventing intrathecal morphine-induced pruritus in such patients. We included 60 consecutive nonbreastfeeding women who were scheduled for elective cesarean delivery. After the administration of spinal anesthesia with bupivacaine and intrathecal morphine 0.15 mg injection, the patients were randomly divided into three groups. Group 1 received placebo (normal saline) IV injection, Group 2 diphenhydramine 30 mg IV injection, and Group 3 ondansetron 0.1 mg/kg IV injection. The incidence of pruritus was significantly lower in the ondansetron group (25%) when compared with that in the placebo group (85%) and in the diphenhydramine group (80%) (both P < 0.05). The postoperative pain score and time to flatus passage were not significantly different among the three groups. There were no headache or extrapyramidal signs associated with ondansetron use. In conclusion, ondansetron prophylaxis significantly reduced the incidence of intrathecal morphine-induced pruritus in patients undergoing cesarean delivery. ⋯ Ondansetron prophylaxis significantly decreases the incidence of pruritus, a common side effect of intrathecal morphine used to treat postcesarean delivery pain.