SEARCH · PubMed Health

Results for “ANESTHETICS”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 883 records · Page 49Linked to original sources

PubMed2000

Comparison of volatile anesthetic effects on actin-myosin cross-bridge cycling in neonatal versus adult cardiac muscle.

BACKGROUND: The neonatal myocardium is more sensitive to volatile anesthetics compared with adults. The greater myocardial sensitivity of neonates may be attributable to greater anesthetic effect on force regulation at the level of the cross-bridge. In the current study, the authors compared the effects of 1 and 2 minimum alveolar concentration (MAC) halothane and sevoflurane on cardiac muscle from 0- to 3-day-old (neonate) and 84-day-old (adult) rats. METHODS: Triton X-100-skinned muscle strips were maximally activated at pCa (negative logarithm of the Ca2+ concentration) of 4.0, and the following were measured in the presence or absence of anesthetic: Rate of force redevelopment after rapid shortening and restretching (ktr) and isometric stiffness at maximal activation and in rigor. The fraction of attached cross-bridges (alphafs) and apparent rate constants for cross-bridge attachment (fapp) and detachment (gapp) were calculated assuming a two-state model for cross-bridge cycling. Anesthetic-induced changes in the mean stiffness per cross-bridge were also estimated from values in rigor versus maximum activation in the presence or absence of anesthetic. RESULTS: Neonatal cardiac muscle displayed significantly smaller alphafs slower ktr and slower fapp compared with adult cardiac muscle; however, gapp was not significantly different. Halothane, and sevoflurane to a significantly lesser extent, decreased alphafs, fapp, and the mean force per cross-bridge and increased gapp to a greater extent in neonates. CONCLUSIONS: These data indicate that weaker force production in neonatal cardiac muscle involves, at least in part, less efficient cross-bridge cycling kinetics. The authors conclude that the greater myocardial sensitivity of neonates to volatile anesthetics reflects, at least in part, a direct inhibition of cross-bridge cycling, especially the rates of cross-bridge attachment and detachment.

Actins↗

PubMed2000

Anesthetic effects on cerebral metabolic rate predict histologic outcome from near-complete forebrain ischemia in the rat.

BACKGROUND: Although reduction of cerebral metabolic rate is thought to contribute to anesthetic neuroprotection, histologic evidence to support this concept has not been provided. In this study, histologic outcome was evaluated in rats subjected to different durations of severe forebrain ischemia while anesthetized with volatile anesthetics that have substantially different effects on cerebral metabolic rate. METHODS: Normothermic rats that underwent fasting were anesthetized with 0.75 minimum alveolar concentration (MAC) isoflurane-60% nitrous oxide (N2O) or 0.75 MAC halothane-60% N2O. Ischemia was induced with use of a combination of bilateral carotid occlusion and controlled hypotension. Rats in the isoflurane group were subjected to 6.5 min or 8.0 min ischemia, whereas the halothane group received 6.5 min ischemia. Histologic damage was assessed 4 days later. RESULTS: With 6.5 min ischemia, mean +/- SD, hippocampal CA1 percent of dead (% dead) neurons was reduced with isoflurane-N2O (45 +/- 18) versus halothane-N2O (60 +/- 23, P = 0. 023). Eight minutes of ischemia increased % dead neurons in the isoflurane-N2O group (60 +/- 17, P = 0.017). There was no difference between the isoflurane 8.0-min and halothane 6.5-min groups (P = 0. 935). A similar pattern was observed in hippocampal CA4 and the neocortex. Striatal damage was not affected by anesthetic or ischemic duration. CONCLUSIONS: At 6.5 min ischemia, isoflurane provided improved outcome versus halothane. Previous research has shown that 0.75 MAC isoflurane-N2O increases the time to onset of ischemic depolarization by 1.5 min and reduces cerebral metabolic rate by 42% versus 0.75 MAC halothane-N2O. In the current study, when the duration of ischemia was increased by 1.5 min in the isoflurane-N2O group, histologic outcome became similar to that in halothane-N2O-anesthetized rats. These results provide evidence that cerebral metabolic rate reduction has an advantageous effect on outcome from severe brain ischemia, but also suggest that such benefit is likely to be small.

Anesthetics, Inhalation↗

PubMed2001

Anesthetic properties of 4-iodopropofol: implications for mechanisms of anesthesia.

BACKGROUND: Positive modulation of gamma-aminobutyric acid type A (GABAA) receptor function is recognized as an important component of the central nervous system depressant effects of many general anesthetics, including propofol. The role for GABAA receptors as an essential site in the anesthetic actions of propofol was recently challenged by a report that the propofol analog 4-iodopropofol (4-iodo-2,6-diisopropylphenol) potentiated and directly activated GABAA receptors, yet was devoid of sedative-anesthetic effects in rats after intraperitoneal injection. Given the important implications of these findings for theories of anesthesia, the authors compared the effects of 4-iodopropofol with those of propofol using established in vivo and in vitro assays of both GABAA receptor-dependent and -independent anesthetic actions. METHODS: The effects of propofol and 4-iodopropofol were analyzed on heterologously expressed recombinant human GABAA alpha1beta2gamma2 receptors, evoked population spike amplitudes in rat hippocampal slices, and glutamate release from rat cerebrocortical synaptosomes in vitro. Anesthetic potency was determined by loss of righting reflex in Xenopus laevis tadpoles, in mice after intraperitoneal injection, and in rats after intravenous injection. RESULTS: Like propofol, 4-iodopropofol enhanced GABA-induced currents in recombinant GABAA receptors, inhibited synaptic transmission in rat hippocampal slices, and inhibited sodium channel-mediated glutamate release from synaptosomes, but with reduced potency. After intraperitoneal injection, 4-iodopropofol did not produce anesthesia in mice, but it was not detected in serum or brain. However, 4-iodopropofol did produce anesthesia in tadpoles (EC50 = 2.5 +/- 0.5 microM) and in rats after intravenous injection (ED50 = 49 +/- 6.2 mg/kg). CONCLUSIONS: Propofol and 4-iodopropofol produced similar actions on several previously identified cellular and molecular targets of general anesthetic action, and both compounds induced anesthesia in tadpoles and rats. The failure of 4-iodopropofol to induce anesthesia in rodents after intraperitoneal injection is attributed to a pharmacokinetic difference from propofol rather than to major pharmacodynamic differences.

Anesthetics, Intravenous↗

PubMed2001

Local anesthetic inhibition of voltage-activated potassium currents in rat dorsal root ganglion neurons.

BACKGROUND: Local anesthetic actions on the K+ channels of dorsal root ganglion (DRG) and dorsal horn neurons may modulate sensory blockade during neuraxial anesthesia. In dorsal horn neurons, local anesthetics are known to inhibit transient but not sustained K+ currents. The authors characterized the effects of local anesthetics on K+ currents of isolated DRG neurons. METHODS: The effects of lidocaine, bupivacaine, and tetracaine on K+ currents in isolated rat DRG neurons were measured with use of a whole cell patch clamp method. The currents measured were fast-inactivating transient current (I(Af)), slow-inactivating transient current (I(As)), and noninactivating sustained current (I(Kn)). RESULTS: One group of cells (type 1) expressed I(Af) and I(Kn). The other group (type 2) expressed I(As) and I(Kn). The diameter of type 2 cells was smaller than that of type 1 cells. Lidocaine and bupivacaine inhibited all three K+ currents. Tetracaine inhibited I(As) and I(Kn) but not I(Af) For bupivacaine, the concentration for half-maximal inhibition (IC50) of I(Kn) in type 2 cells was lower than that for I(Kn) in type 1 cells (57 vs. 121 microM). Similar results were obtained for tetracaine (0.6 vs. 1.9 mM) and for lidocaine (2.2 vs. 5.1 mM). CONCLUSIONS: Local anesthetics inhibited both transient and sustained K+ currents in DRG neurons. Because K+ current inhibition is known to potentiate local anesthetic-induced impulse inhibition, the lower IC50 for I(Kn) of small type 2 cells may reflect preferential inhibition of impulses in nociceptive neurons. The overall modulatory actions of local anesthetics probably are determined by their differential effects on presynaptic (DRG) and postsynaptic (dorsal horn neurons) K+ currents.

Anesthetics, Local↗

PubMed2002

Transcutaneous electrical stimulation of an auricular acupuncture point decreases anesthetic requirement.

BACKGROUND: German anesthesiologists have long used transcutaneous electrical stimulation of an acupuncture point near the tragus to reduce anesthetic requirement in unblinded and uncontrolled trials. This is known as auricular electrically stimulated analgesia. The authors therefore tested the hypothesis that auricular electrically stimulated analgesia reduces anesthetic requirement. METHODS: In a randomized, double-blind, crossover trial, volunteers were anesthetized twice with desflurane. Electrical stimulation of an auricular acupuncture point in the vicinity of the tragus was used on 1 randomly assigned day, and no electrical stimulation of the same point was used on the other study day. Treatment consisted of bilateral electrical stimulation of the lateralization control point, 3 cm anterior to the tragus. The 10-mA current was set to 299 Hz on the dominant side of the face and to 149 Hz on the contralateral side. Anesthetic requirement was determined by the Dixon up-and-down method and was defined by the average desflurane concentration required to prevent purposeful movement of the extremities in response to noxious electrical stimulation. RESULTS: Ten men and 10 women completed the protocol. Electrical stimulation of the lateralization control point reduced anesthetic requirement by 11 +/- 7% (P < 0.001), with the reduction being similar in women and men. Women required more desflurane to prevent movement on the control day than the men (5.5 +/- 1.0 vs. 4.6 +/- 0.6 vol%; P = 0.028). CONCLUSION: This double-blinded trial with an objective outcome demonstrates that electrical stimulation of the lateralization control point significantly reduces anesthetic requirement.

Acupuncture Points↗

PubMed2002

Distribution of local anesthetic in axillary brachial plexus block: a clinical and magnetic resonance imaging study.

BACKGROUND: There is an unsettled discussion about whether the distribution of local anesthetic is free or inhibited when performing brachial plexus blocks. This is the first study to use magnetic resonance imaging (MRI) to help answer this question. METHODS: Thirteen patients received axillary block by a catheter-nerve stimulator technique. After locating the median nerve, a total dose of 50 ml local anesthetic was injected via the catheter in four divided doses of 1, 4, 15, and 30 ml. Results of sensory and motor testing were compared with the spread of local anesthetic as seen by MRI scans taken after each dose. The distribution of local anesthetic was described with reference to a 20-mm diameter circle around the artery. RESULTS: Thirty minutes after the last dose, only two patients demonstrated analgesia or anesthesia in the areas of the radial, median, and ulnar nerve. At that time, eight of the patients had incomplete spread of local anesthetic around the artery, as seen by MRI. Their blocks were significantly poorer than those of the five patients with complete filling of the circle, although incomplete blocks were also present in the latter group. CONCLUSION: This study demonstrated that MRI is useful in examining local anesthetic distribution in axillary blocks because it can show the correlation between MRI distribution pattern and clinical effect. The cross-sectional spread of fluid around the brachial-axillary artery was often incomplete-inhibited, and the clinical effect often inadequate.

Adult↗

PubMed2002

Differential effects of anesthetics on mitochondrial K(ATP) channel activity and cardiomyocyte protection.

BACKGROUND: Mitochondrial adenosine triphosphate-sensitive potassium (mitoK(ATP)) channels play a pivotal role in mediating cardiac preconditioning. The effects of intravenous anesthetics on this protective channel have not been investigated so far, but would be of importance with respect to experimental as well as clinical medicine. METHODS: Live cell microscopy was used to visualize and measure autofluorescence of flavoproteins, a direct reporter of mitoK(ATP) channel activity, in response to the direct and highly selective mitoK(ATP) channel opener diazoxide, or to diazoxide following exposure to various anesthetics commonly used in experimental and clinical medicine. A cellular model of ischemia with subsequent hypoosmolar trypan blue staining served to substantiate the effects of the anesthetics on mitoK(ATP) channels with respect to myocyte viability. RESULTS: Diazoxide-induced mitoK(ATP) channel opening was significantly inhibited by the anesthetics R-ketamine, and the barbiturates thiopental and pentobarbital. Conversely, urethane, 2,2,2-trichloroethanol (main metabolite of alpha-chloralose and chloral hydrate), and the opioid fentanyl potentiated the channel-opening effect of diazoxide, which was abrogated by coadministration of chelerythrine, a specific protein kinase C inhibitor. S-ketamine, propofol, xylazine, midazolam, and etomidate did not affect mitoK(ATP) channel activity. The significance of these modulatory effects of the anesthetics on mitoK(ATP) channel activity was substantiated in a cellular model of simulated ischemia, where diazoxide-induced cell protection was mitigated by R-ketamine and the barbiturates, while urethane, 2,2,2-trichloroethanol, and fentanyl potentiated myocyte protection. CONCLUSIONS: These results suggest distinctive actions of individual anesthetics on mitoK(ATP) channels and provide evidence that the choice of background anesthesia may play a role in cardiac protection in both experimental and clinical medicine.

Adenosine Triphosphate↗

PubMed2002

General anesthetics do not affect release of the neuropeptide cholecystokinin from isolated rat cortical nerve terminals.

BACKGROUND: General anesthetics inhibit evoked release of classic neurotransmitters. However, their actions on neuropeptide release in the central nervous system have not been well characterized. METHODS: The effects of representative intravenous and volatile anesthetics were studied on the release of sulfated cholecystokinin 8 (CCK8s), a representative excitatory neuropeptide, from isolated rat cerebrocortical nerve terminals (synaptosomes). Basal, elevated KCl depolarization-evoked and veratridine-evoked release of CCK8s from synaptosomes purified from rat cerebral cortex was evaluated at 35 degrees C in the absence or presence of extracellular Ca2+. CCK8s released into the incubation medium was determined by enzyme-linked immunoassay after filtration. RESULTS: Elevation of extracellular KCl concentration (to 15-30 mM) or veratridine (10-20 microm) stimulated Ca2+ -dependent CCK8s release. Basal, elevated KCl- or veratridine-evoked CCK8s release was not affected significantly by propofol (12.5-50 microm), pentobarbital (50 and 100 microm), thiopental (20 microm), etomidate (20 microm), ketamine (20 microm), isoflurane (0.6-0.8 mM), or halothane (0.6-0.8 mMm). CONCLUSIONS: Clinically relevant concentrations of several classes of general anesthetics did not affect basal, KCl-evoked, or veratridine-evoked CCK8s release from isolated rat cortical nerve terminals. This is in contrast to the demonstrable effects of certain general anesthetics on the release of amino acid and catecholamine transmitters. These transmitter-specific presynaptic effects of general anesthetics suggest that anesthetic-sensitive presynaptic targets are not common to all transmitter classes.

Anesthetics, General↗

PubMed2003

Role of protein kinase C, Ca2+/calmodulin-dependent protein kinase II, and mitogen-activated protein kinases in volatile anesthetic-induced relaxation in newborn rabbit pulmonary artery.

BACKGROUND: This study examined the responsiveness of skinned pulmonary arteries from newborn rabbit to volatile anesthetics and the role of protein kinase C (PKC), Ca2+/calmodulin-dependent protein kinase II (CaMKII), and the downstream effectors, mitogen-activated protein kinases (ERK1/2 and p38). METHODS: Pulmonary arterial strips from 9- to 12-day-old rabbits were mounted on force transducers and treated with saponin ("skinned" strips). The skinned strips were activated by pCa 6.3 until force reached a steady state (control). Isoflurane or halothane was then administered. The result (test) was expressed as a percentage of the control. Inhibitors included bisindolylmaleimide (Ca2+-dependent and -independent PKC), Gö6976 (Ca2+-dependent PKC), CKIINtide (CaMKII), KN-93 (CaMKII), PD98059 (MEK/ERK1/2), and SB203580 (p38). RESULTS: The anesthetics dose-dependently decreased pCa-induced force (4-32% for 1-5% isoflurane; 17-76% for 1-3% halothane). The inhibitors of PKC (bisindolylmaleimide and Gö6976) and MEK/ERK1/2 (PD98059) completely prevented the relaxation induced by 3% isoflurane and partially prevented that induced by 2% and 3% halothane with the same effective inhibitor concentrations. In contrast, the effective concentration of CaMKII inhibitors was a direct function of the anesthetic concentration for different inhibitors (KN-93 for isoflurane and CKIINtide for halothane), and that of the p38 inhibitor (SB20358) was a direct function of both anesthetics. CONCLUSIONS: In Ca2+-clamped skinned pulmonary arterial strips from newborn rabbits, the anesthetics induce relaxation, which is prevented by the PKC inhibitors MEK/ERK/12, CaMKII, and p38. It is proposed that the anesthetic-induced relaxation is via cPKC/MEK/ERK1/2 and CaMKII/p38 pathways and, in addition, via CaMKII-p/MLCK-p(-)/MLC-p(-) for halothane.

Anesthetics, Inhalation↗

PubMed2003

Calreticulin mediates anesthetic sensitivity in Drosophila melanogaster.

BACKGROUND: Various species, e.g., Caenorhabditis elegans, Drosophila melanogaster, and mice, have been used to explore the mechanisms of action of general anesthetics in vivo. The authors isolated a Drosophila mutant, ethas311, that was hypersensitive to diethylether and characterized the calreticulin (crc) gene as a candidate of altered anesthetic sensitivity. METHODS: Molecular analysis of crc included cloning and sequencing of the cDNA, Northern blotting, and in situ hybridization to accomplish the function of the gene and its mutation. For anesthetic phenotype assay, the 50% anesthetizing concentrations were determined for ethas311, revertants, and double-mutant strains (wild-type crc transgene plus ethas311). RESULTS: Expression of the crc 1.4-kb transcript was lower in the mutant ethas311 than in the wild type at all developmental stages. The highest expression at 19 h after pupation was observed in the brain of the wild type but was still low in the mutant at that stage. The mutant showed resistance to isoflurane as well as hypersensitivity to diethylether, whereas it showed the wild phenotype to halothane. Both mutant phenotypes were restored to the wild type in the revertants and double-mutant strains. CONCLUSION: ethas311 is a mutation of low expression of the Drosophila calreticulin gene. The authors demonstrated that hypersensitivity to diethylether and resistance to isoflurane are associated with low expression of the gene. In Drosophila, calreticulin seems to mediate these anesthetic sensitivities, and it is a possible target for diethylether and isoflurane, although the predicted anesthetic targets based on many studies in vitro and in vivo are the membrane proteins, such as ion channels and receptors.

Anesthetics↗

PubMed2005

Anesthetics inhibit membrane receptor coupling to the Gq/11 heterotrimeric G protein in airway smooth muscle.

BACKGROUND: Some anesthetics relax airway smooth muscle in part by inhibiting acetylcholine-induced increases in Ca2+ sensitivity, an effect associated with inhibition of guanosine nucleotide exchange at the alpha subunit of the Gq/11 (Galphaq/11) heterotrimeric G protein. This study tested the hypothesis that these anesthetic effects are not unique to the muscarinic receptor but are a general property of the heptahelical receptors that increase Ca2+ sensitivity in airway smooth muscle. METHODS: Anesthetic effects on agonist-induced increases in Ca2+ sensitivity were measured in porcine airway smooth muscle strips permeabilized with S. aureus alpha-toxin. Anesthetic effects on basal (without agonist stimulation) and agonist-promoted Galphaq/11 guanosine nucleotide exchange were determined in crude membranes prepared from porcine airway smooth muscle. The nonhydrolyzable, radioactive form of guanosine 5'-triphosphate was used as the reporter for nucleotide exchange at Galphaq/11. RESULTS: Acetylcholine, endothelin-1, and histamine caused a concentration-dependent increase in Ca2+ sensitivity. Halothane (0.67 +/- 0.07 mM) and hexanol (10 mM) significantly inhibited the increase in Ca2+ sensitivity induced by each agonist. Each agonist also caused a time- and concentration-dependent increase in Galphaq/11 nucleotide exchange. Neither anesthetic had an effect on basal Galphaq/11 nucleotide exchange, whereas halothane and hexanol significantly inhibited the increase in Galphaq/11 nucleotide exchange promoted by each agonist. CONCLUSION: These data suggest that inhibition of agonist-promoted guanosine nucleotide exchange at Galphaq/11 by some anesthetics may be a general property of heptahelical receptors involved cellular processes mediated by Galphaq/11, including muscarinic, endothelin-1, and histamine receptor activation of Ca2+ sensitivity.

Acetylcholine↗

PubMed2006

New insights into the mechanism of methoxyflurane nephrotoxicity and implications for anesthetic development (part 1): Identification of the nephrotoxic metabolic pathway.

BACKGROUND: Methoxyflurane nephrotoxicity results from biotransformation; inorganic fluoride is a toxic metabolite. Concern exists about potential renal toxicity from volatile anesthetic defluorination, but many anesthetics increase fluoride concentrations without consequence. Methoxyflurane is metabolized by both dechlorination to methoxydifluoroacetic acid (MDFA, which may degrade to fluoride) and O-demethylation to fluoride and dichloroacetatic acid. The metabolic pathway responsible for methoxyflurane nephrotoxicity has not, however, been identified, which was the aim of this investigation. METHODS: Experiments evaluated methoxyflurane metabolite formation and effects of enzyme induction or inhibition on methoxyflurane metabolism and toxicity. Rats pretreated with phenobarbital, barium sulfate, or nothing were anesthetized with methoxyflurane, and renal function and urine methoxyflurane metabolite excretion were assessed. Phenobarbital effects on MDFA metabolism and toxicity in vivo were also assessed. Metabolism of methoxyflurane and MDFA in microsomes from livers of pretreated rats was determined in vitro. RESULTS: Phenobarbital pretreatment increased methoxyflurane nephrotoxicity in vivo (increased diuresis and blood urea nitrogen and decreased urine osmolality) and induced in vitro hepatic microsomal methoxyflurane metabolism to inorganic fluoride (2-fold), dichloroacetatic acid (1.5-fold), and MDFA (5-fold). In contrast, phenobarbital had no influence on MDFA renal effects in vivo or MDFA metabolism in vitro or in vivo. MDFA was neither metabolized to fluoride nor nephrotoxic. Barium sulfate diminished methoxyflurane metabolism and nephrotoxicity in vivo. CONCLUSIONS: Fluoride from methoxyflurane anesthesia derives from O-demethylation. Phenobarbital increases in methoxyflurane toxicity do not seem attributable to methoxyflurane dechlorination, MDFA toxicity, or MDFA metabolism to another toxic metabolite, suggesting that nephrotoxicity is attributable to methoxyflurane O-demethylation. Fluoride, one of many metabolites from O-demethylation, may be toxic and/or reflect formation of a different toxic metabolite. These results may have implications for interpreting anesthetic defluorination, volatile anesthetic use, and methods to evaluate anesthetic toxicity.

Anesthetics, Inhalation↗

PubMed2006

New insights into the mechanism of methoxyflurane nephrotoxicity and implications for anesthetic development (part 2): Identification of nephrotoxic metabolites.

BACKGROUND: Methoxyflurane nephrotoxicity results from its metabolism, which occurs by both dechlorination (to methoxydifluoroacetic acid [MDFA]) and O-demethylation (to fluoride and dichloroacetic acid [DCAA]). Inorganic fluoride can be toxic, but it remains unknown why other anesthetics, commensurately increasing systemic fluoride concentrations, are not toxic. Fluoride is one of many methoxyflurane metabolites and may itself cause toxicity and/or reflect formation of other toxic metabolite(s). This investigation evaluated the disposition and renal effects of known methoxyflurane metabolites. METHODS: Rats were given by intraperitoneal injection the methoxyflurane metabolites MDFA, DCAA, or sodium fluoride (0.22, 0.45, 0.9, or 1.8 mmol/kg followed by 0.11, 0.22, 0.45, or 0.9 mmol/kg on the next 3 days) at doses relevant to metabolite exposure after methoxyflurane anesthesia, or DCAA and fluoride in combination. Renal histology and function (blood urea nitrogen, urine volume, urine osmolality) and metabolite excretion in urine were assessed. RESULTS: Methoxyflurane metabolite excretion in urine after injection approximated that after methoxyflurane anesthesia, confirming the appropriateness of metabolite doses. Neither MDFA nor DCAA alone had any effects on renal function parameters or necrosis. Fluoride at low doses (0.22, then 0.11 mmol/kg) decreased osmolality, whereas higher doses (0.45, then 0.22 mmol/kg) also caused diuresis but not significant necrosis. Fluoride and DCAA together caused significantly greater tubular cell necrosis than fluoride alone. CONCLUSIONS: Methoxyflurane nephrotoxicity seems to result from O-demethylation, which forms both fluoride and DCAA. Because their co-formation is unique to methoxyflurane compared with other volatile anesthetics and they are more toxic than fluoride alone, this suggests a new hypothesis of methoxyflurane nephrotoxicity. This may explain why increased fluoride formation from methoxyflurane, but not other anesthetics, is associated with toxicity. These results may have implications for the interpretation of clinical anesthetic defluorination, use of volatile anesthetics, and the laboratory methods used to evaluate potential anesthetic toxicity.

Anesthesiology↗

PubMed1994

General anesthetic techniques.

General anesthesia is the most common form of anesthetic management for ambulatory surgery. Patients, in general, prefer general anesthesia because it is less anxiety provoking. During the last decade, the availability of several short-acting agents with high clearance has made general anesthetic techniques much safer and more predictable for outpatients. Besides, general anesthesia today is associated with a quick and full recovery with minimal postoperative side effects. Proper preanesthetic psychological and, when necessary, pharmacological preparation as well as proper selection of anesthetic agents are the keys to the success of general anesthetic technique for ambulatory surgery. Although both TIVA and total inhalation anesthetic techniques have their advocates, balanced anesthesia is most popular. The introduction of several new agents (e.g., propofol, desflurane, vecuronium, atracurium, mivacurium, rocuronium, alfentanil, ondansetron, ketorolac) has made ambulatory general anesthesia less challenging and more interesting. In the future, the new anesthetic sevoflurane, and the new opioid remifentanil, may prove useful for ambulatory anesthesia. The LMA has all but revolutionized airway management during general anesthesia for ambulatory surgery.

Ambulatory Surgical Procedures↗

PubMed2005

Comparison of topical lidocaine/prilocaine anesthetic cream and local infiltration of 2% lidocaine for episioplasty in mares.

Local anesthesia and tissue inflammation associated with lidocaine infiltration and lidocaine/prilocaine topical anesthetic cream for episioplasty in mares were compared. Twenty-two mares were randomly assigned to lidocaine or lidocaine/prilocaine topical anesthetic cream treatment groups. Perineum and vulva were cleaned, 8-12 g (approximately 1 g/cm per side of vulva) of topical anesthetic cream was applied, and the area was covered by plastic wrap 30 min prior to beginning procedure. Alternately, lidocaine was injected (1 mL) every centimeter just prior to the procedure. Episioplasty was conducted using standard methods, but employing simple interrupted sutures. Horses were not sedated and use of a twitch was recorded. Four millimeter punch biopsies were harvested 1, 3, and 10 days following episioplasty and scored for degree of inflammation by a blinded pathologist. Clinical inflammation scores were assigned when biopsies were obtained. Seven of 11 horses receiving lidocaine infiltration required twitching, but none of the horses that received the anesthetic cream required twitching. Six of 11 and seven of 11 of the lidocaine and anesthetic cream groups, respectively, required twitching for episioplasty. Except for the clinical scores on day 3, no statistical differences for clinical and histopathologic scores between samples from the two treatment groups for a given day were identified. Use of lidocaine/prilocaine topical anesthetic cream was as effective as lidocaine infiltration in providing local anesthesia when performing episioplasty in mares. Its use decreased the need for twitching horses as well as the risk of deformation of the labia caused by lidocaine infiltration.

Administration, Cutaneous↗

PubMed1995

Long-term evaluation of usefulness of skin and incremental challenge tests in patients with history of adverse reaction to local anesthetics.

A variety of adverse reactions to local anesthetics has been described, some of which are thought to be allergic. Different protocols of prick and intradermal skin tests as well as subcutaneous challenge tests are used to select a local anesthetic which can safely be used. Their long-term effectiveness has not yet been assessed. Twenty-eight patients with a history of adverse reaction to local anesthetics were evaluated over a 3-year period. Loss of consciousness occurred in eight patients, skin reaction in nine, and vagal symptoms in eight. Various reactions were recorded in the remaining three patients. Rapid spontaneous recovery was the rule, suggesting that immediate allergic reaction and, in particular, anaphylactic reaction were unlikely. Investigation allowed the selection of a tolerated anesthetic in all cases. Reexposure occurred in 19 patients 16-50 months after evaluation and 6.8 +/- 5.5 years after the first reaction. No patient presented a second reaction. In conclusion, adverse reactions to local anesthetics seem to be, in most cases, not allergic in nature. Evaluation protocols are effective in selecting an agent susceptible to tolerance, but are time consuming. However, they probably contribute to an important reassurance effect that is likely to increase tolerance to subsequent local anesthetic administration. Simplification of the protocols and better patient selection are proposed.

Adult↗

PubMed1987

Choice of anesthetic alters the circulatory shock pattern as gauged by conscious rat endotoxemia.

A standardized rat endotoxin shock model was used to assess the differential effects of four commonly used anesthetics upon hemodynamics before and during endotoxin shock. Forty-nine male Sprague-Dawley rats weighing 307 +/- 4 g were divided into five groups:freely-moving conscious, enflurane (2%), isoflurane (1.4%), pentobarbital (6 mg.kg-1.h-1 i.v.), and ketamine (45 mg.kg-1.h-1 i.v.). Anesthetic doses were chosen as 1.0 MAC equivalent. Anesthetized rats were intubated and ventilated with oxygen. The right carotid artery was cannulated with a thermocouple-catheter for aortic blood pressure, heart rate, and thermodilution cardiac output measurements. The right jugular vein was cannulated for measurement of central venous pressure and for i.v. injections. Data were collected over a 30-min baseline period and for 4 h after an i.v. bolus of endotoxin (40 mg.kg-1, LD100 within 24 h). Gross small intestinal pathology was rated on a 0-4 scale. Anesthetic effects were judged in terms of significant deviations from the awake data on each parameter. Despite differing patterns, total deviations were similar for enflurane, ketamine, and pentobarbital, although the latter drug was the least preferable due to particularly high systemic vascular resistance. Significantly less hemorrhagic small intestinal pathology occurred with enflurane. Ketamine offered no advantage over the inhalation anesthetics. Among the four anesthetics tested, results were closest to the awake pattern with isoflurane anesthesia, thus making it the logical choice for hemodynamic studies in experimental shock research.

Anesthetics↗

PubMed1997

Effects of volatile anesthetics on the calcium ionophore A23187-mediated alterations in hepatic flow and metabolism in the perfused liver in fasted rats.

Alterations in intracellular calcium homeostasis have been implicated in heptic injury. Volatile anesthetics modulate the homeostasis of intracellular calcium. The effects of volatile anesthetics on the hemodynamic and metabolic alterations induced by the calcium ionophore A23187 were studied using isolated liver perfusion in fasted rats. The liver was isolated from 24 hr-fasted male Sprague-Dawley rats, and perfused through the portal vein at a constant pressure of 1.2 kPa in a recirculating perfusion-aeration system. Halothane, isoflurane and sevoflurane were administered at 2%, 3% and 4.4%, respectively. All volatile anesthetics maintained basal hepatic flow, reduced oxygen consumption, and transiently enhanced net lactate production. A23187 at initial concentrations of 0.8 to 3.2 microM decreased hepatic flow and oxygen consumption in a dose-dependent manner, and enhanced lactate production. All anesthetics significantly attenuated the decreases in hepatic flow and oxygen consumption after administration of A23187 at 1.6 microM. None of the anesthetics significantly influenced the A23187-induced enhancement of net lactate production. Volatile anesthetics may attenuate the hepatic vasoconstriction and oxygen debt induced by intracellular calcium overload.

Anesthetics, Inhalation↗