Anesthesia and analgesia
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Anesthesia and analgesia · Feb 2004
Randomized Controlled Trial Clinical TrialRapid onset of cutaneous anesthesia with EMLA cream after pretreatment with a new ultrasound-emitting device.
In this randomized, double-blinded, placebo-controlled, crossover trial of 42 human subjects, we examined the speed of onset of cutaneous anesthesia by eutectic mixture of local anesthetics (EMLA) cream after brief (approximately 10-s) pretreatment of the underlying skin with low-frequency (55 kHz) ultrasound. Four treatments were compared: ultrasound pretreatment followed by application of 1 g EMLA or placebo cream for 5 min, 10 min, 15 min, and 60 min without ultrasound pretreatment as positive control. Pain was tested by pricks with a 20 g needle. Pain scores and patient preference for EMLA or placebo cream were measured at each time point. Based on both pain scores and patient preference, cutaneous anesthesia was achieved in the EMLA groups as compared with placebo at all time points. After ultrasound pretreatment and then 5, 10, or 15 min after EMLA cream application, pain scores and overall preference were statistically indistinguishable from EMLA cream application for 60 min (without ultrasound pretreatment). There were no significant adverse effects. Low-frequency ultrasound pretreatment appears to be safe and effective in producing rapid onset of EMLA cream in this model, with results as early as 5 min. ⋯ A prospective, randomized, double-blinded, placebo-controlled clinical trial demonstrated rapid onset of cutaneous anesthesia by pretreatment of the skin with ultrasound before application of EMLA cream.
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Anesthesia and analgesia · Feb 2004
Randomized Controlled Trial Clinical TrialThe effects of remifentanil and gabapentin on hyperalgesia in a new extended inflammatory skin pain model in healthy volunteers.
We tested the responsiveness of measures of hyperalgesia in a model of UVB-induced inflammatory hyperalgesia with remifentanil, gabapentin, and the combination of both drugs in a double-blinded, active placebo-controlled, 4-way-crossover design in 16 volunteers. A circular skin area was irradiated with UVB-light 20 h before the application of gabapentin (600 mg) and 2 h later remifentanil (0.08 microg.kg(-1).min(-1), 40 min). In the sunburn spots we observed stable decreases of the heat pain perception thresholds (HPPT, mean difference, 4.45 degrees C; 95% confidence interval [CI], 3.32 degrees -5.59 degrees ) and heat pain tolerance thresholds (HPTT; mean difference, 5.43 degrees C; 95% CI, 4.50 degrees -6.35 degrees ) compared with normal skin. Further, large areas of mechanical hyperalgesia to pinprick adjacent to the erythema spots developed in all subjects. Overall remifentanil increased the HPPT (mean increase, 2.47 degrees C; 95% CI, 1.86 degrees -3.09 degrees, P < 0.001) and HPTT (mean increase, 3.18 degrees C; 95% CI, 2.65 degrees -3.71 degrees, P < 0.001) and reduced the area of secondary hyperalgesia by 59% (mean decrease, 5326 mm(2); 95% CI, 4233-6419 mm(2), P < 0.001) compared with placebo. In the sunburn remifentanil markedly increased the HPTT by 86% compared with normal skin (additional increase, 2.57 degrees C; 95% CI, 1.71 degrees -3.43 degrees). This different effect was not seen in the HPPT. With the exception of a small increase of HPTT in the sunburn (P = 0.02) gabapentin had no noticeable effect on either hyperalgesia. In conclusion, opioid analgesia was reliably demonstrated in this new extended pain model. ⋯ Opioid analgesia was reliably demonstrated in a new inflammatory model of primary and secondary hyperalgesia. Gabapentin showed no antihyperalgesic and no opioid-enhancing effect in this model.
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Anesthesia and analgesia · Feb 2004
Randomized Controlled Trial Comparative Study Clinical TrialEpidural levobupivacaine 0.1% or ropivacaine 0.1% combined with morphine provides comparable analgesia after abdominal surgery.
Ropivacaine appears attractive for epidural analgesia because it produces less motor block than racemic bupivacaine. The potential benefits of levobupivacaine with regard to motor blockade require further investigations. In this study, we compared the efficacy, dose requirements, side effects, and motor block observed with epidural levobupivacaine and ropivacaine when given in combination with small-dose morphine for 60 h after major abdominal surgery. Postoperatively, 50 patients were randomly allocated, in a double-blinded manner, to patient-controlled epidural analgesia with the same settings and without basal infusion, using 0.1% levobupivacaine or 0.1% ropivacaine. Both were combined with an epidural infusion of 0.1 mg/h morphine. Pain scores, side effects, motor block, and local anesthetic consumption were measured for 60 h. Pain scores measured on a 100-mm visual analog scale were approximately 20 mm at rest and 40 mm during mobilization in both groups. Bromage scores were 1 for all patients after the fourth postoperative hour. Consumption of levobupivacaine and ropivacaine were similar: 344 +/- 178 mg levobupivacaine versus 347 +/- 199 mg ropivacaine 48 h postoperatively. On postoperative day 2, 19 patients in the ropivacaine group versus 12 in the levobupivacaine group were able to ambulate (P < 0.05). No difference was noted concerning incidence of side effects. We conclude that when used as patient-controlled epidural analgesia and combined with small-dose epidural morphine, 0.1% levobupivacaine and 0.1% ropivacaine produce comparable postoperative analgesia with a similar incidence of side effects. ⋯ Small concentrations (0.1%) of epidural levobupivacaine and ropivacaine combined with morphine (0.1 mg/h) produce comparable analgesia and have similar side effects for similar dose requirements.
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Anesthesia and analgesia · Feb 2004
Randomized Controlled Trial Clinical TrialA placebo-controlled randomized crossover trial of the N-methyl-D-aspartic acid receptor antagonist, memantine, in patients with chronic phantom limb pain.
In the present study we investigated the effect of the N-methyl-D-aspartic acid (NMDA) receptor antagonist memantine (30 mg/d) on the intensity of chronic phantom limb pain (PLP) and cortical reorganization. In 8 patients with chronic PLP, memantine was tested in a placebo-controlled double-blinded crossover trial of 4 wk duration per trial. The intensity of PLP was rated hourly by the patients on a visual analog scale during baseline and both treatment periods. At the same time points, the functional organization of the primary somatosensory cortex (SI) was determined by neuromagnetic source imaging. In comparison to baseline and placebo, the NMDA receptor antagonist had no effect on the intensity of chronic PLP. In none of the periods were significant changes in the functional organization of SI observed. Although the conclusions regarding the clinical effect are limited because of the small sample size, the data indicate that in the studied dosage the NMDA receptor antagonist memantine is ineffective in the treatment of chronic PLP and is also ineffective for the reduction of associated neural plasticity in the primary SI. ⋯ NMDA receptors play a substantial role in central nervous system changes underlying neuropathic pain. In a placebo-controlled double-blinded study we tested the effect of 30 mg memantine on chronic phantom limb pain and pain-associated cortical reorganization.
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Anesthesia and analgesia · Feb 2004
Randomized Controlled Trial Clinical TrialThe median effective dose of nefopam and morphine administered intravenously for postoperative pain after minor surgery: a prospective randomized double-blinded isobolographic study of their analgesic action.
The aim of this study was to characterize the nature of analgesic interaction between nefopam and morphine administered i.v. for postoperative pain after minor surgery. To do so, we defined the median effective analgesic dose (ED(50)) for each drug and also the median ED(50) of their combination and compared them using the isobolographic method. Determination of median effective doses was performed by the up-and-down sequential drug administration in a two-stage study. First, in a prospective, randomized, double-blinded study, we enrolled 60 patients with mild to moderate pain after minor surgery; this was followed by an open study enrolling 30 patients. The end-point was a pain score less than 3 on a Numerical Pain Scale (0-10). Initial doses were 16 mg in group N, 5 mg in group M, and 7.5 mg of N combined with 2.5 mg of M in group N+M. The testing interval was 2 mg in group N, 1 mg in group M, and 1.5 mg of N combined with 0.5 mg of M in group N+M. ED(50) (95% confidence interval) was 5 mg (4-6 mg) for morphine, 18 mg (16-18 mg) for nefopam, and 4 mg (3.5-4.5 mg) with 12 mg (10.5-13.5 mg) for the combination of morphine and nefopam administered at a 3:1 dose ratio. Isobolographic analysis demonstrated a significant infra-additive interaction. The incidence of side effects did not differ significantly among morphine, nefopam, and their combination. These findings suggest that the combination of nefopam and morphine does not offer any advantage compared to each drug administered i.v. or alone after minor surgery. This study is the first to define the ED(50) of nefopam and morphine in postoperative patients. In conclusion, the addition of nefopam has a morphine-sparing effect, but the combination is infra-additive. ⋯ Pharmacologic interaction between nefopam and morphine shows infra-additivity but their combination may be clinically useful as morphine consumption is decreased in postoperative patients.