Anesthesia and analgesia
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Anesthesia and analgesia · Mar 1999
The effects of general anesthetics on excitatory and inhibitory synaptic transmission in area CA1 of the rat hippocampus in vitro.
It is unclear whether general anesthetics induce enhancement of neural inhibition and/or attenuation of neural excitation. We studied the effects of pentobarbital (5 x 10(-4) mol/L), propofol (5 x 10(-4) mol/L), ketamine (10(-3) mol/L), halothane (1.5 vol%), and isoflurane (2.0 vol%) on both excitatory and inhibitory synaptic transmission in rat hippocampal slices. Excitatory or inhibitory synaptic pathways were isolated using pharmacological antagonists. Extracellular microelectrodes were used to record electrically evoked CA1 neural population spikes (PSs). In the presence of the gamma-aminobutyric acid type A (GABA(A)) receptor antagonist (bicuculline), the inhibitory actions of pentobarbital and propofol were completely antagonized, whereas those of ketamine, halothane, and isoflurane were only partially blocked. To induce the N-methyl-D-aspartate (NMDA) receptor-mediated PS (NMDA PS), the non-NMDA and GABA(A) receptors were blocked in the absence of Mg2+. Ketamine, halothane, and isoflurane decreased the NMDA PS, and pentobarbital and propofol had no effect on the NMDA PS. The non-NMDA receptor-mediated PS (non-NMDA PS) was examined using the antagonists for the NMDA and GABA(A) receptors. Volatile, but not i.v., anesthetics reduced the non-NMDA PS. These findings indicate that pentobarbital and propofol produce inhibitory actions due to enhancement in the GABA(A) receptor; that ketamine reduces NMDA receptor-mediated responses and enhances GABA(A) receptor-mediated responses; and that halothane and isoflurane modulate GABA(A), NMDA, and non-NMDA receptor-mediated synaptic transmission. ⋯ Volatile anesthetics modulate both excitatory and inhibitory synaptic transmission of in vitro rat hippocampal pathways, whereas i.v. anesthetics produce more specific actions on inhibitory synaptic events. These results provide further support the idea that general anesthetics produce drug-specific and distinctive effects on different pathways in the central nervous system.
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Anesthesia and analgesia · Mar 1999
Randomized Controlled Trial Multicenter Study Clinical TrialA double-blinded evaluation of propacetamol versus ketorolac in combination with patient-controlled analgesia morphine: analgesic efficacy and tolerability after gynecologic surgery.
We assessed the relative morphine consumption in a combined analgesic regimen (on-demand morphine plus the nonopioids propacetamol or ketorolac) after gynecologic surgery. Two hundred women randomly received two i.v. doses of propacetamol 2 g or ketorolac 30 mg in a double-blinded, double-dummy trial. Patients were monitored for 12 h, and the following efficacy variables were assessed: total dose of morphine, pain intensity, and global efficacy. Safety and tolerability were evaluated by the occurrence of adverse events, especially the presence and intensity of gastrointestinal symptoms. Hemostatic variables were measured 30 and 60 min after the first infusion; arterial blood pressure, heart and respiratory rates, sedation scores, and renal and hepatic function were also assessed. Total morphine requirements were not significantly different between the propacetamol (10.6 +/- 4.8 mg) and ketorolac (10.2 +/- 4.4 mg) groups. The evolution of pain intensity and the global efficacy also showed similar patterns in the two groups: 70.2% of patients in the propacetamol group rated the efficacy as "good/ excellent" compared with 68.2% in the ketorolac group. There were no clinically significant changes in vital signs or laboratory values and no observed differences between the two groups, although ketorolac slightly, but not significantly, prolonged the bleeding time. Epigastric pain was present in 9% and 15% of patients receiving propacetamol and ketorolac, respectively. There were two adverse events in the propacetamol group and four in the ketorolac group. Propacetamol demonstrates an efficacy similar to that of ketorolac and has an excellent tolerability after gynecologic surgery. ⋯ Propacetamol and ketorolac, combined with patient-controlled analgesia morphine, show similar analgesic efficacy after gynecologic surgery. Morphine consumption and pain scores were comparable in the two studied groups. Propacetamol is as effective as ketorolac and has an excellent tolerability after gynecologic surgery.