Anesthesia and analgesia
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Anesthesia and analgesia · Aug 2005
The long term myotoxic effects of bupivacaine and ropivacaine after continuous peripheral nerve blocks.
Compared with bupivacaine, acute myotoxicity of ropivacaine is less severe. Thus, in this study we compared the long term myotoxic effects of both drugs in a clinically relevant setting. Femoral nerve catheters were inserted in anesthetized pigs, and either 20 mL of bupivacaine (5 mg/mL) or ropivacaine (7.5 mg/mL) was injected. Subsequently, bupivacaine (2.5 mg/mL) and ropivacaine (3.75 mg/mL) were continuously infused (8 mL/h) over 6 h. Control animals were treated with corresponding volumes of normal saline. After 7 and 28 days, respectively, muscle samples were dissected at the former injection sites, and histological patterns of muscle damage were blindly scored (0 = no damage to 3 = marked lesions/myonecrosis) and compared. No morphological tissue changes were detected in control animals. In the observed period, both local anesthetics induced morphologically identical patterns of calcific myonecrosis, formation of scar tissue, and a marked rate of fiber regeneration. However, bupivacaine's effects were constantly more pronounced than those of ropivacaine. These data show that both drugs induce irreversible skeletal muscle damage in a clinically relevant model, and confirm the exceeding rate of myotoxicity of bupivacaine. However, the clinical impact of these long term myotoxic effects still has to be assessed. ⋯ In a period of 4 wk after peripheral nerve block, both long-acting local anesthetics, bupivacaine and ropivacaine, produced calcific myonecrosis suggestive of irreversible skeletal muscle damage. In comparison with ropivacaine, however, the extent of bupivacaine-induced muscle lesions was significantly larger.
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Anesthesia and analgesia · Aug 2005
The impact of acoustic stimulation on the AEP monitor/2 derived composite auditory evoked potential index under awake and anesthetized conditions.
The AEP Monitor/2 features an auditory evoked potential (AEP) and electroencephalogram (EEG)-derived hybrid index of the patient's hypnotic state. The composite AEP index (AAI) is preferably calculated from the AEP, but in case of low signal quality it is based entirely on the spontaneous EEG. We investigated the impact of auditory input on the AAI in 16 patients with correctly positioned headphones for acoustic stimulation and headphones disconnected from the patient's ears under awake and anesthetized conditions. The AAI and the Narcotrend Index (NI), another EEG-based measure of hypnotic depth, were recorded simultaneously. AAI values under awake and anesthetized conditions were higher with correctly positioned headphones than with headphones disconnected from the patient's ears (P < 0.05) but remained within the range indicating the patient's actual hypnotic state as given by the manufacturer of the monitor. Under awake conditions with correctly positioned headphones we observed frequent fluctuations between AEP-derived and EEG-derived AAI, whereas with headphones disconnected from the patient's ears the AAI calculation was completely EEG based. Acoustic stimulation had no impact on the Narcotrend Index. Although relevant misinterpretations of the patient's hypnotic state as a consequence of a turnover from AEP-derived to EEG-derived AAI values should not occur, an improved harmonization of the two methods of indexing would be desirable. ⋯ The AEP Monitor/2 generates an Index (AAITM) indicating the patient's hypnotic state by analyzing either auditory evoked potentials (AEP) or spontaneous electroencephalographic (EEG) activity. We demonstrate that, though significantly different under AEP-derived or EEG-derived conditions, AAI values remain within the range indicating the patient's actual hypnotic state as given by the manufacturer of the device.
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Several anesthetic drugs are nicotinic antagonists at or below levels used for anesthesia, including ketamine and volatile anesthetics. In contrast, propofol does not inhibit nicotinic receptors. To determine the potential behavioral ramifications of nicotinic inhibition by ketamine, we determined the doses of ketamine required to induce immobility, impair the righting reflex, and cause analgesia in the absence and presence of several nicotinic ligands. Propofol was used as a control in similar experiments. When used as a sole anesthetic drug, 383 +/- 22 mg/kg ketamine intraperitoneally (IP) was required for immobility and 180 +/- 17 mg/kg IP impaired righting reflex. Propofol, 371 +/- 34 mg/kg IP, induced immobility whereas 199 mg/kg IP inhibited the righting reflex. Nicotinic antagonists had no effect on the dose of propofol or ketamine required for either end-point. When nociceptive responses were tested at subhypnotic doses, no pronociceptive or antinociceptive phase was identified for propofol, whereas analgesia was induced at ketamine doses larger than 60 mg/kg IP. The broad-spectrum nicotinic antagonist mecamylamine enhanced the analgesic action of ketamine. These findings are different than those seen with volatile anesthetics, where nicotinic inhibition is thought to be responsible for a pronociceptive action. Such a phase is possibly obscured by analgesia induced as a result of N-methyl-d-aspartic acid antagonism by ketamine. ⋯ Ketamine and volatile anesthetics, but not propofol, inhibit neuronal nicotinic acetylcholine receptors in clinically relevant concentration ranges. Nicotinic inhibition by ketamine is not related to its immobilizing or sedating effects but may play a role in ketamine's analgesic action.
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Anesthesia and analgesia · Aug 2005
The inhibitory effects of sevoflurane on angiotensin II- induced, p44/42 mitogen-activated protein kinase-mediated contraction of rat aortic smooth muscle.
Sevoflurane dilates blood vessels and reduces arterial blood pressure in a dose-dependent manner. Angiotensin II (Ang II) is one of the primary regulators of vascular tension and arterial blood pressure, and the p44/42 mitogen-activated protein kinases (p44/42 MAPK) are involved in Ang II-mediated vascular smooth muscle contraction. We designed this study to examine the effects of sevoflurane on Ang II-induced, p44/42 MAPK-mediated contraction of rat aortic smooth muscle. The effects of the p44/42 MAPK kinase (MEK1/2) inhibitor, PD 098059 (10(-5) molar [M], 5 x 10(-5) M and 10(-4) M), and sevoflurane (1.7%, 3.4%, and 5.1%) on Ang II-induced contraction and p44/42 MAPK phosphorylation were tested in rat aortic smooth muscle, using isometric force measurement and Western blot analysis, respectively. Ang II induced both a transient contractile response and phosphorylation of p44/42 MAPK, which were significantly attenuated by PD 098059 (P < 0.05-0.01). Sevoflurane inhibited Ang II-induced contractile response in a dose-dependent manner (P < 0.05 and 0.01 in response to 3.4% and 5.1% sevoflurane, respectively). Sevoflurane also dose-dependently depressed Ang II-elicited p44/42 MAPK phosphorylation (P < 0.01 in response to 3.4% and 5.1% sevoflurane). These results suggest that the inhibitory effect of sevoflurane on Ang II-induced vasoconstriction is, at least in part, caused by the inhibition of the p44/42 MAPK-mediated signaling pathway. ⋯ The present study demonstrates that sevoflurane can dose-dependently inhibit both angiotensin II (Ang II)-induced contraction and p44/42 MAPK phosphorylation of rat aortic smooth muscle. These data suggest that sevoflurane-produced inhibition of Ang II-induced vasoconstriction is, at least in part, caused by depression of the p44/42 MAPK-mediated signaling pathway.
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Anesthesia and analgesia · Aug 2005
A novel technique for experimental stellate ganglion block in rats.
A stellate ganglion block (SGB) is routinely performed in a clinical setting for the treatment of sympathetically maintained pain syndromes. However, the cardiovascular effects of SGB have not been well defined. The purpose of the present study was to develop a new technique of SGB in a rat model. Our new technique of SGB is a posterior percutaneous approach and uses the cartilaginous process of the C7 spinous process as a landmark. Twenty-six Sprague-Dawley female rats were divided into six groups. Group I (n = 4) underwent right sided SGB, Group II (n = 5) underwent left-sided SGB, and Group III (n = 5) underwent bilateral SGB using bupivacaine 0.25%. Three additional sham groups (n = 4 in each group) served as controls to each of the three treatment groups. Ipsilateral eyelid droop (ptosis) was observed in all animals that underwent SGB with bupivacaine. Heart rate decreased significantly for up to 45 min after bilateral SGB compared with control groups. However, this value did not change in rats after unilateral SGB. In 9 additional rats, we evaluated the accuracy of SGB by injecting methylene blue to stain the right (n = 3), left (n = 3), and bilateral SGB (n = 3). At autopsy, 11 of 12 SG were stained post-methylene blue injection. We conclude from our study that our new approach, posterior percutaneous SGB is a reliable technique that can be used for further studies. ⋯ We describe a new technique for stellate ganglion block in rats that may be used in future studies to investigate the role of cervical sympathetic nervous system (especially the stellate ganglion) in regulating sympathetically maintained pain and myocardial function.