Anesthesiology
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Comparative Study
Absorption characteristics of transdermally administered fentanyl.
Fentanyl was administered intravenously and transdermally to eight surgical patients to determine the systemic bioavailability and rate of absorption of the transdermally administered drug. Serum fentanyl concentrations reached a plateau approximately 14 h after placement of the transdermal fentanyl delivery system. This plateau was maintained until removal of the system at 24 h. ⋯ At the time of removal of the transdermal fentanyl system, 1.07 +/- 0.43 mg of drug remained in this depot. Systemic fentanyl bioavailability was found to be 0.92 +/- 0.33, with no evidence of significant cutaneous metabolism or degradation by the skin's bacterial flora. The transdermal administration of fentanyl produces relatively constant serum fentanyl concentrations for significant periods of time in the postsurgical patient requiring analgesic therapy.
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The toxicity of mepivacaine in chronically instrumented nonpregnant and pregnant sheep was evaluated, and compared with data from previous studies of the toxicity of other local anesthetics. Thirteen preparations were studied, seven nonpregnant (NP) and six pregnant (P). Mepivacaine 2 mg.kg-1.min-1 was infused at a constant rate into the femoral vein until toxic manifestations occurred, in the following sequence: convulsions, hypotension, respiratory arrest, and circulatory collapse. ⋯ In contrast, the proportion of bound bupivacaine was 73% in NP and 51% in P, a significant difference. These protein binding data suggest that, although lethal concentrations of bupivacaine, determined in the previous study, were higher in NP than in P animals, concentrations of free drug were similar. Thus, the difference between the two drugs may be related to gestational increases in the availability of free drug in the case of bupivacaine.
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Randomized Controlled Trial Clinical Trial
Prolongation of succinylcholine block by metoclopramide.
Laboratory and clinical evidence of the inhibition of plasma cholinesterase by metoclopramide was demonstrated. When succinylcholine is used as the substrate and the product choline assayed by choline oxidase-peroxidase-quinone dye colorimetry, the rate of the choline production as optical density change was reduced to 50% by 19.5 X 10(-6) M metoclopramide at 20 degrees C. Prolongation of neuromuscular blockade produced by concurrent administration of succinylcholine and metoclopramide was studied in 22 patients aged between 18 and 40 years undergoing elective gynecological surgery. ⋯ Recovery times were again measured and found to be prolonged in patients receiving metoclopramide compared with those not receiving metoclopramide (P less than 0.05). Metoclopramide has no intrinsic neuromuscular blocking activity, but its ability to inhibit plasma cholinesterase probably is the mechanism by which it prolongs succinylcholine block. Reducing the dose of succinylcholine may be appropriate when metoclopramide is given concurrently.