Locoregional versus general anesthesia in carotid surgery: is there an impact on perioperative myocardial ischemia? Results of a prospective monocentric randomized trial.
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PURPOSE: The incidence of cardiac morbidity and mortality in patients who undergo carotid surgery ranges from 0.7% to 7.1%, but it still represents almost 50% of all perioperative complications. Because no data are available in literature about the impact of the anesthetic technique on such complications, a prospective randomized monocentric study was undertaken to evaluate the role of local anesthesia (LA) and general anesthesia (GA) on cardiac outcome. METHODS: From November 1995 to February 1998, 107 patients were classified by the cardiologist as cardiac patients (IHD; history of myocardial infarction, previous myocardial revascularization procedures, or myocardial ischemia documented by means of positive electrocardiogram [ECG] stress test results) or noncardiac patients (NIHD; no history of chest pain or negative results for an ECG stress test). The patients were operated on after the randomization for the type of anesthesia (general or local). Continuous computerized 12-lead ECG was performed during the operative procedure and 24 hours postoperatively. The end points of the study were ECG modifications (upsloping or downsloping more than 2 mm) of the sinus tachycardia (ST) segment. RESULTS: Fifty-five patients were classified as IHD, and 52 were classified as NIHD. Twenty-seven of the 55 IHD patients (49%) and 24 of 52 NIHD patients (46%) were operated on under GA. Thirty-six episodes of myocardial ischemia occurred in 22 patients (20.5%). Episodes were slightly more frequent (58%) and longer in the postoperative period (intraoperative, 10 +/- 5 min; postoperative, 60 +/- 45 min; P <. 001). As expected, the prevalence of myocardial ischemia was higher in the group of cardiac patients than in noncardiac group (15 of 55 patients [27%] vs 7 of 52 patients [13%]; P <.02). By comparing the two anesthetic techniques in the overall population, we found a similar prevalence of patients who had myocardial ischemia (GA, 12 of 52 [23%]; LA, 10 of 55 [18%]; P = not significant) and a similar number of ischemic episodes per patient (GA, 1.5 +/- 0.4; LA, 1.8 +/- 0.6; P = not significant). Episodes of myocardial ischemia were similarly distributed in intraoperative and postoperative periods in both groups. It is relevant that under GA, IHD patients represent most of the population who suffered myocardial ischemia (83%). On the contrary, in the group of patients operated on under LA, the prevalence was equally distributed in the two subpopulations. CONCLUSION: The results confirm the different hemodynamic impact of the two anesthetic techniques. Patients who received LA had a rate of myocardial ischemia that was half that of patients who had GA. The small number of cardiac complications do not permit us to make any definitive conclusion on the impact of the two anesthetic techniques on early cardiac morbidity, but the relationship between perioperative ischemic burden and major cardiac events suggests that LA can be used safely, even in high-risk patients undergoing carotid endarterectomy. (+info)
Local anesthetic anchoring to cardiac sodium channels. Implications into tissue-selective drug targeting.
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Local anesthetics inhibit Na+ channels in a variety of tissues, leading to potentially serious side effects when used clinically. We have created a series of novel local anesthetics by connecting benzocaine (BZ) to the sulfhydryl-reactive group methanethiosulfonate (MTS) via variable-length polyethylether linkers (L) (MTS-LX-BZ [X represents 0, 3, 6, or 9]). The application of MTS-LX-BZ agents modified native rat cardiac as well as heterologously expressed human heart (hH1) and rat skeletal muscle (rSkM1) Na+ channels in a manner resembling that of free BZ. Like BZ, the effects of MTS-LX-BZ on rSkM1 channels were completely reversible. In contrast, MTS-LX-BZ modification of heart and mutant rSkM1 channels, containing a pore cysteine at the equivalent location as cardiac Na+ channels (ie, Y401C), persisted after drug washout unless treated with DTT, which suggests anchoring to the pore via a disulfide bond. Anchored MTS-LX-BZ competitively reduced the affinity of cardiac Na+ channels for lidocaine but had minimal effects on mutant channels with disrupted local anesthetic modification properties. These results establish that anchored MTS-LX-BZ compounds interact with the local anesthetic binding site (LABS). Variation in the linker length altered the potency of channel modification by the anchored drugs, thus providing information on the spatial relationship between the anchoring site and the LABS. Our observations demonstrate that local anesthetics can be anchored to the extracellular pore cysteine in cardiac Na+ channels and dynamically interact with the intracellular LABS. These results suggest that nonselective agents, such as local anesthetics, might be made more selective by linking these agents to target-specific anchors. (+info)
Intracranial pressure changes with different doses of lignocaine under general anaesthesia.
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The effect of intravenous lignocaine on intracranial pressure (ICP) was studied on thirty patients of either sex, aged above 5 years and scheduled for elective ventriculoperitoneal shunt surgery. The patients were randomly divided into 3 groups, which received intravenous lignocaine in the dose of 1 mg, 1.5 mg and 2 mg/kg body weight respectively. Intracranial pressure, heart rate, ECG, arterial pressure and arterial blood gases were monitored at various intervals for a period of 30 minutes. Maximum decrease in ICP was seen at 2 minutes after IV lignocaine in all the three groups (p<0. 001). The fall in ICP was significantly more in group II and group III (35.65% and 37.5% respectively) as compared to group I (17.47%) (p<0.001). This fall in ICP in all the three groups persisted below the basal level, throughout the study period. None of the groups showed any significant change in the heart rate, but a statistically significant fall in arterial pressure was observed in group III (p<0. 05). In conclusion intravenous lignocaine, in a dose of 1.5 mg/kg, causes significant fall in ICP without causing any untoward cardiovascular effects and is recommended for routine clinical use. (+info)
Basolateral amygdala is involved in modulating consolidation of memory for classical fear conditioning.
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Previous findings indicate that the basolateral amygdala complex of nuclei (BLC) is involved in modulating (i.e., enhancing or impairing) memory consolidation for aversive training such as inhibitory avoidance. The present study examined whether the BLC also modulates the consolidation of memory for classical fear conditioning in which a specific context is paired with footshock. Adult male rats with bilateral cannulae targeting the BLC were allowed, first, to habituate in a Y maze that had differently shaped and textured arms. On the next day the rats were placed in one maze arm (shock arm), and they received four unsignaled footshocks. In Experiment 1, immediately after the training some rats received BLC inactivation with lidocaine (10 microgram/0.2 microliter per side), and control rats received buffered saline. In Experiment 2, rats received immediate post-training intra-BLC infusions of the muscarinic receptor agonist oxotremorine (10 ng/0.2 microliter per side) or saline. On a 24 hr retention test each rat was placed in a "safe" arm of the maze and allowed to access all maze arms. Lidocaine-treated rats had impaired memory for the classical fear conditioning when they were compared with the saline-treated controls: they spent less time freezing, entered the shock arm more readily and more often, and spent more time in it. In contrast, oxotremorine-treated rats had a stronger memory for the context-footshock association as assessed by all measures of memory. Thus, post-training treatments affecting BLC function modulate memory for Pavlovian contextual fear conditioning in a manner similar to that found with other types of training. (+info)
Point mutations at N434 in D1-S6 of mu1 Na(+) channels modulate binding affinity and stereoselectivity of local anesthetic enantiomers.
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Voltage-gated Na(+) channels are the primary targets of local anesthetics (LAs). Amino acid residues in domain 4, transmembrane segment 6 (D4-S6) form part of the LA binding site. LAs inhibit binding of the neurotoxin batrachotoxin (BTX). Parts of the BTX binding site are located in D1-S6 and D4-S6. The affinity of BTX-resistant Na(+) channels mutated in D1-S6 (mu1-N434K, mu1-N437K) toward several LAs is significantly decreased. We have studied how residue mu1-N434 influences LA binding. By using site-directed mutagenesis, we created mutations at mu1-N434 that vary the hydrophobicity, aromaticity, polarity, and charge and investigated their influence on state-dependent binding and stereoselectivity of bupivacaine. Wild-type and mutant channels were transiently expressed in human embryonic kidney 293t cells and investigated under whole-cell voltage-clamp. For resting channels, bupivacaine enantiomers showed a higher potency in all mutant channels compared with wild-type channels. These changes were not well correlated with the physical properties of the substituted residues. Stereoselectivity was small and almost unchanged. In inactivated channels, the potency of bupivacaine was increased in mutations containing a quadrupole of an aromatic group (mu1-N434F, mu1-N434W, mu1-N434Y), a polar group (mu1-N434C), or a negative charge (mu1-N434D) and was decreased in a mutation containing a positive charge (mu1-N434K). In mutation mu1-N434R, containing the positively charged arginine, the potency of S(-)-bupivacaine was selectively decreased, resulting in a stereoselectivity (stereopotency ratio) of 3. Similar results were observed with cocaine but not with RAC 109 enantiomers. We propose that in inactivated channels, residue mu1-N434 interacts directly with the positively charged moiety of LAs and that D1-S6 and D4-S6 form a domain-interface site for binding of BTX and LAs in close proximity. (+info)
No enhancement of sensory and motor blockade by neostigmine added to mepivacaine axillary plexus block.
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BACKGROUND: Intrathecal neostigmine induces analgesia but also several side effects. Recently, 500 microg neostigmine administered intraarticularly was shown to produce postoperative analgesia without side effects. The authors' goal was to determine whether 500 microg neostigmine added to mepivacaine in axillary plexus block prolongs postoperative analgesia. In addition, they wanted to determine the incidence of side effects in patients undergoing hand surgery. METHODS: Sixty-nine outpatients scheduled for carpal tunnel syndrome repair with axillary plexus block were randomly assigned to one of three groups that received saline solution in the axillary plexus and subcutaneously (group 1), 500 microg neostigmine in the axillary plexus and saline solution subcutaneously (group 2), or saline solution in the axillary plexus and 500 microg neostigmine subcutaneously (group 3). Sensory and motor block in the four hand nerve distributions were assessed every 5 min for 30 min The duration of the sensory and motor blocks were assessed after operation. Side effects were also recorded. RESULTS: Neostigmine had no effect on sensory and motor block in any of the four nerve distributions, nor did it increase the median duration of sensory block (215 min; range, 120-330 min) compared with group 1 (247 min; range, 190-287 min) or group 3 (236 min; range, 160-280 min). Motor block was slightly shorter (P = 0.045) in group 3 (190 min; range, 135-285 min) compared with group 1 (218 min; range, 145257 min) and group 2 (215 min; range, 105-343 min). Gastrointestinal side effects occurred in 30% of patients in both neostigmine groups but not in group 1 (P < 0.05). CONCLUSIONS: This study suggests that 500 microg neostigmine added to mepivacaine in axillary plexus block does not prolong postoperative sensory block, but it does cause a relatively high incidence of side effects. These two findings raise doubts about the use of neostigmine associated with local anesthetics for plexus neural block. (+info)
Bupivacaine augments intrathecal fentanyl for labor analgesia.
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BACKGROUND: fentanyl has been shown to be an effective analgesic for labor; this study investigated the analgesic effect of low-dose bpivacaine added to intrathecal fentanyl for labor analgesia METHODS: Ninety parturients in active labor who requested regional analgesia were randomized to receive an intrathecal injection of either fentanyl, 25 microg; bupivacaine, 1.25 mg, with fentanyl, 25 microg; or bupivacaine, 2.5 mg, with fentanyl, 25 microg, as part of a combined spinal-epidural technique. Visual analog pain scores were recorded before and at intervals after injection until the patient requested further analgesia. Maternal blood pressure and fetal heart rate were recorded before and at intervals after injection. Lower-extremity muscle strength was tested before and 30 min after injection; anesthetic level to cold sensation and the presence and severity of pruritus were recorded. RESULTS: Duration of analgesia was longer in the group receiving bupivacaine, 2.5 mg, and fentanyl, 25 microg, than the group receiving plain fentanyl (108 vs. 92 min; P < 0.05). Onset of analgesia was faster in both groups receiving bupivacaine compared with plain fentanyl (P < 0.05). No differences in muscle strength after injection were found in any group, although anesthetic levels to cold were documented in all patients in the bupivacaine groups, and 21 of 30 in the plain fentanyl group. Baseline fetal heart rates did not change after injection in any group, and maternal blood pressure was unchanged. CONCLUSIONS: The addition of 2.5 mg isobaric bupivacaine to 25 microg fentanyl for intrathecal labor analgesia modestly increases duration and speeds onset of analgesia compared with plain intrathecal fentanyl. (+info)
Relative potencies of bupivacaine and ropivacaine for analgesia in labour.
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We have used the technique of randomized, double-blind sequential allocation to compare the minimum local analgesic concentrations (MLAC) of epidural bupivacaine and ropivacaine for women in the first stage of labour. The test bolus was 20 ml of local anaesthetic solution. The concentration was determined by the response of the previous woman to a higher or lower concentration of local anaesthetic, according to up-down sequential allocation. Efficacy was assessed using a 100-mm visual analogue pain score (VAPS). The test solution had to achieve a VAPS of 10 mm or less to be judged effective. For bupivacaine, MLAC was 0.093 (95% CI 0.076-0.110)% w/v, and for ropivacaine, 0.156 (95% CI 0.136-0.176)%w/v (P < 0.0001, 95% CI difference 0.036-0.090). The analgesic potency of ropivacaine was 0.60 (0.47-0.75) relative to bupivacaine. Claims for reduced toxicity and motor block must be considered with differences in analgesic potency in mind. (+info)