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PubMed1991

Anesthetics affect membrane heterogeneity.

A computer-simulation study is performed on a simple but general molecular model of the interaction of general and local anesthetics with lipid membranes. In the neighborhood of the gel-to-fluid membrane phase transition it is found that anesthetics have a strong effect on the heterogeneity of the membrane-inducing regions of locally high anesthetics concentration. This leads to a broadening of the specific heat peak and a maximum in the membrane/water partition coefficient. These results are in accordance with available experimental data for volatile general anesthetics like halothane and local anesthetics like cocaine derivatives.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed1998

Gating kinetics of Shaker K+ channels are differentially modified by general anesthetics.

The ShakerB K+ channel was used as a model voltage-gated channel to probe the interaction of volatile general anesthetics with gating mechanisms. The effects of three anesthetics, chloroform (CHCl3), isoflurane, and halothane, were studied using recombinant native and mutant Shaker channels expressed in Xenopus oocytes. Gating currents and macroscopic ionic currents were recorded with the cut-open oocyte voltage-clamp technique. The effects of CHCl3 and isoflurane on gating kinetics of noninactivating mutants were opposite, whereas halothane had no effect. The effects on ionic currents were also agent dependent: CHCl3 and halothane produced a reduction of the macroscopic conductance, whereas isoflurane increased it. The results indicate that the gating machinery of the channel is mostly insensitive to the anesthetics during activation until near the open state. The effects on the conductance are mainly due to changes in the transitions in and out of the open state. The data give support to direct protein-anesthetic interactions. The magnitude and nature of the effects invite reconsideration of Shaker-like K+ channels as important sites of action of general anesthetics.

Amino Acid Substitution↗

PubMed2003

Hemispheric synchronized sounds and intraoperative anesthetic requirements.

Hemispheric synchronization is currently promoted as a treatment for preoperative anxiety and for reduction of intraoperative anesthetic and analgesic consumption. We designed this study to examine the effect of Hemisync sounds on anesthetic hypnotic depth. After obtaining informed consent, we randomized subjects undergoing general anesthesia and outpatient surgery into two groups: the treatment group received Hemisync sounds (n = 31), and the control group received a blank cassette tape (n = 29). Both groups received the intervention in the preoperative area and during the surgical procedure. Subjects underwent a propofol-based anesthetic regimen, and propofol doses required for the induction and maintenance of anesthesia were recorded. A bispectral index monitor was used to ensure that the hypnotic component of the anesthetic state was the same in all patients. We found no differences in the amount of propofol used during the induction of anesthesia (2.49 +/- 0.59 mg/kg versus 2.60 +/- 0.59 mg/kg; P = 0.48) or the maintenance of anesthesia (0.141 +/- 0.02 mg x kg(-1) x min(-1) versus 0.146 +/- 0.04 mg x kg(-1) x min(-1); P = 0.62) between the Hemisync and control groups. We also found no differences between the Hemisync group and the control group for participants with high state anxiety (P = not significant). We conclude that Hemisync sounds do not reduce the hypnotic component of the anesthetic state of patients undergoing general anesthesia and surgery.

Acoustic Stimulation↗

PubMed1997

New non-cocaine-containing topical anesthetics compared with tetracaine-adrenaline-cocaine during repair of lacerations.

OBJECTIVE: To compare the effectiveness of three new topical anesthetics that do not contain cocaine (prilocaine-phenylephrine, tetracaine-phenylephrine [tetraphen], and tetracaine-lidocaine-phenylephrine) to that of tetracaine-adrenaline-cocaine (TAC) during laceration repair in children. DESIGN: Prospective, randomized, double-blind clinical trial. SETTING: The emergency department of an urban children's hospital. PARTICIPANTS: Children 1 year of age or older with a laceration </= 5 cm in length that required suturing. Intervention. A total of 240 children were randomly assigned to one of four treatment groups. OUTCOME MEASURES: Pain felt during suturing was scored by suture technicians, research assistants, parents, and patients >/= 5 years of age using a visual analogue scale (VAS). Suture technicians, research assistants, and parents also scored pain using a seven-point Likert scale. In addition, suture technicians completed an anesthetic effectiveness scale. RESULTS: There was consistently no difference demonstrated between the effectiveness of tetraphen and that of TAC for each outcome measure of each observer group. A statistically significant difference was seen among anesthetics when comparing VAS and Likert scale scores of suture technicians and Likert scale scores of research assistants. Based on post hoc analyses, these statistically significant differences were between TAC and prilocaine-phenylephrine (suture technician VAS and Likert scale) and between TAC and tetracaine-lidocaine-phenyl-ephrine (suture technician Likert scale), but not between TAC and tetraphen. When power analyses were performed using alpha = 0.05 and beta = 0.20, it was possible to detect a difference of 1.2 VAS units for each of the observer groups. Based on anesthetic effectiveness scale scores, the three new topical preparations collectively performed significantly better on the face and scalp than on the extremities (relative risk = 1.83; 95% confidence interval 1.20 < relative risk < 2.79). CONCLUSION: This study demonstrated the effectiveness and safety of three new non-cocaine-containing topical anesthetics. Consistently, there was no statistical difference demonstrated between the effectiveness of tetraphen and that of TAC for each outcome measure of each observer group. Tetraphen offers an effective alternative to TAC during laceration repair in children.

Adolescent↗

PubMed2005

[Anesthetic management of a patient in whom one-lung ventilation occurred due to an incorrectly positioned stent].

Stents are inserted for severe stenosis of the trachea owing to malignant tumors, but an incorrectly positioned stent can cause airway obstruction. Here, we report the anesthetic management of a patient undergoing removal of an incorrectly positioned stent. A 56-year-old man had a stent inserted in the trachea for stenosis caused by a tumor. One month later, he was scheduled for reinsertion of a stent for tracheal stenosis owing to growth of the tumor, but the stent was inserted in the left main bronchus interfering ventilation to the right lung. Therefore, removal of the stent under general anesthesia was scheduled. As the stent was to be removed from an incision in the cricoid, we had to maintain deep anesthesia to maintain immobility, keeping spontaneous respiration in case we could not ventilate during surgery. Since inhaled anesthetics are insufficient to maintain deep anesthesia, we anesthetized the patient with an intravenous anesthetic, sevoflurane and continuous propofol infusion. Propofol allows spontaneous respiration better than opioids. With this method we were able to anesthetize the patient maintaining spontaneous respiration and oxygenation with stable vital signs during surgery.

Anesthesia, General↗

PubMed2006

[Comparison of the painless effect of four anesthetic methods during pulpal treatment].

OBJECTIVE: To compare the painless effect of four anesthetic methods during opening pulp cavity and undergoing pulpectomy for acute or chronic pulpitis. METHODS: 80 teeth of 80 patients were randomly allocated into four groups. Each group had 20 teeth. Anesthetic methods applied four different groups included block anesthesia of nerve, supraperiosteal infiltration, periodontal membrane injection and intrapulpal injection. Anesthesia doses were recorded and the pierced points, the zones of pain, the time of anesthesia action, the time of anesthesia persistence and the degrees of anesthesia were evaluated with four levels synthetic evaluation standard of anesthesia. RESULTS: Compared with periodontal membrane injection and intrapulpal injection, block anesthesia of nerve and supraperiosteal infiltration had the later time of anesthesia action and the longer time of anesthesia persistence (P<0.05). In four anesthetic methods, block anesthesia of nerve had the best painless effect (P<0.05). CONCLUSION: Four anesthetic methods have their own superiorities, and we should select proper anesthetic methods in clinical work.

Adult↗

PubMed1989

[Applied pharmacology of anesthetics].

Inhalation anesthetics, intravenously applied anesthetics, opiates, muscle relaxants and local anesthetics are the most commonly used anesthetic drugs. From the direct anesthetic effects interactions with other organ systems and functions, especially those involved in vital functions such as the pulmonary and cardio-vasculary systems, must be distinguished. Although the safety-margins for individual drugs vary, side effects are minimal on appropriate dosage and use. Substance-related complications, such as severe hepatic damage or malignant hyperthermia, are rare. Procedure-related differences (general or local anesthesia) were not found for post-operative morbidity and mortality, nor was there a detectable impairment of concentration and mnestic performance.

Anesthesia, Inhalation↗

PubMed1997

Anesthetic effects of tiletamine-zolazepam, alone or in combination with butorphanol, in goats.

OBJECTIVE: To evaluate anesthetic effects of tiletamine-zolazepam (TZ), alone or in combination with butorphanol, in goats undergoing laparotomy for embryo collection. DESIGN: Randomized clinical trial with crossover design. ANIMALS: 9 adult female goats. PROCEDURE: Goats were anesthetized twice: once with TZ (5.5 mg/kg [2.5 mg/lb] of body weight, i.v.) and once with tiletamine-zolazepam and butorphanol (0.1 mg/kg [0.045 mg/lb], i.v.). Additional doses of TZ (0.5 to 1.0 mg/kg [0.23 to 0.45 mg/lb], i.v.] were administered as needed to maintain a surgical anesthetic plane. Time to sternal recumbency was recorded, and quality of induction was scored. Arterial pressures, heart rate, respiratory rate, and rectal temperature were recorded every 5 minutes; arterial blood samples were collected every 30 minutes. Oxygen was insufflated if estimated saturation of hemoglobin in peripheral arterial blood with oxygen was < 90%; intermittent positive-pressure ventilation was performed if goats became apneic. Muscle relaxation, quality of anesthesia, and eye signs were scored every 15 minutes during anesthesia. Anesthesia time was recorded, and quality of recovery and degree of postoperative analgesia were scored. Plasma cortiso concentration was measured before induction, immediately after extubation, and 2 hours after extubation. RESULTS: Induction was rapid and smooth. Five goats regurgitated, 3 required supplemental oxygen, and 1 required intermittent positive-pressure ventilation, but none of the goats became hypotensive. Muscle relaxation and quality of anesthesia were adequate. Goats recovered from anesthesia without complications. We did not detect any significant differences between anesthetic regimens for any of the variables measured, except bicarbonate concentration and base excess. CLINICAL IMPLICATIONS: TZ at a dose of 5.5 mg/kg was satisfactory for anesthetic induction in goats; additional doses can be given to extend anesthesia time, but addition of butorphanol at a dose of 0.1 mg/kg to this regimen does not seem to provide any measurable benefit. An oxygen source and a means of assisting ventilation should be available.

Analgesics, Opioid↗

PubMed1977

Neural blockade by local anesthetics.

Local anesthetics block nerve impulse propagation by occluding transmembrane sodium channels, so preventing depolarization. First, the uncharged lipid-soluble anesthetic base pentrates the membrane; then the positively charged cation binds to anionic components of the sodium channel's internal axoplasmic mouth. Though primarily a carrier, the base contributes to blockade by causing the membrane to swell, so pinching the sodium channels. Dissolved in water, local anesthetic salt crystals dissociate into anesthetic cation and base-proportional to the drug's fixed pKa and the tissue's variable pH. The cation-base concentration ration is critical to optimal neural blockade. If there is too little base, few anesthetic molecules will penetrate to the neural target; if too little cation, few sodium channels will be plugged.

Anesthetics, Local↗

PubMed2005

Local anesthetic sympathetic blockade for complex regional pain syndrome.

BACKGROUND: Local anesthetic blockade of the sympathetic chain is widely used to treat reflex sympathetic dystrophy (RSD) and causalgia. These two pain syndromes are now conceptualized as variants of a single entity: complex regional pain syndrome (CRPS). A recent meta-analysis of the topic has been published. However, this study only evaluated studies in English language and therefore it could have overlooked some randomized controlled trials. OBJECTIVES: This systematic review had three objectives: to determine the likelihood of pain alleviation after sympathetic blockade with local anesthetics in the patient with CRPS; to assess how long any benefit persists; and to evaluate the incidence of adverse effects of the procedure. SEARCH STRATEGY: We searched the Cochrane Pain, Palliative and Supportive Care Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, LILACS, and conference abstracts of the World Congresses of the International Association for the Study of Pain. Bibliographies from retrieved articles were also searched for additional studies. SELECTION CRITERIA: We considered for inclusion randomized controlled trials that evaluated the effect of sympathetic blockade with local anesthetics in children or in adult patients to treat RSD, causalgia, or CRPS. DATA COLLECTION AND ANALYSIS: The outcomes of interest were the number of patients who obtained at least 50% of pain relief shortly after sympathetic blockade (30 minutes to 2 hours) and 48 hours or later. We also assessed the presence of adverse effects in each treatment arm. A random effects model was used to combine the studies. MAIN RESULTS: Two small randomized double blind cross over studies that evaluated 23 subjects were found. The combined effect of the two trials produced a relative risk (RR) to achieve at least 50% of pain relief 30 minutes to 2 hours after the sympathetic blockade of 1.17 (95% CI 0.80-1.72). It was not possible to determine the effect of sympathetic blockade on long-term pain relief because the authors of the two studies evaluated different outcomes. AUTHORS' CONCLUSIONS: This systematic review revealed the scarcity of published evidence to support the use of local anesthetic sympathetic blockade as the 'gold standard' treatment for CRPS. The two randomized studies that met inclusion criteria had very small sample sizes, therefore, no conclusion concerning the effectiveness of this procedure could be drawn. There is a need to conduct randomized controlled trials to address the value of sympathetic blockade with local anesthetic for the treatment of CRPS.

Adult↗

PubMed1990

Cardiac catheterization in the patient with history of allergy to local anesthetics.

Patients with a history of allergic reactions to local anesthetic drugs present a difficult problem during evaluation for cardiac catheterization procedures. In the worst cases the procedure may be deferred, or even performed without local anesthesia. In the vast majority of patients an acceptable agent for safe local anesthetic use can be found. Skin testing beginning with very dilute solutions of preservative-free local anesthetic agent may be administered easily. This report describes the practical aspects of skin testing and local anesthetic agent selection in patients with a history of allergic reaction to local anesthetic drugs.

Adult↗

PubMed1980

Effects of anesthetics on sulfate transport in the red cell.

We measured the effect of anesthetics on sulfate transport in the human erythrocyte and have found that a wide variety of chemical classes of anesthetics, including the anesthetic steroid alphaxalone, inhibit sulfate transport in human erythrocytes at concentrations paralleling the concentrations that block nerve conduction. These experiments suggest that anesthetics act through a general mechanism and that the sulfate transport system in the red blood cell is a good model for studying the mechanism of action of anesthetics.

Anesthetics↗

PubMed1991

Interfacial dehydration by anesthetics: an electrocapillary study of surface charge density of adsorbed monolayer.

We have proposed that anesthetics destruct the hydration shell of macromolecules irrespective of lipid membranes or proteins. These macromolecular structures are supported by the hydrogen-bonded matrix of water molecules. A loss of this support destabilizes the membranes and proteins. The disordered structures are suboptimal for the assigned biological functions, and anesthesia may ensue. We postulated that the dehydration is prompted mainly by the decrease in the interactions of the surface charges with the water dipole. To prove or disprove the above hypothesis, this study measured the effect of volatile anesthetics (chloroform, halothane, and enflurane) on the surface charge density in adsorbed monolayers by an electrocapillary method. The oil phase was methylisobutylketone (MIBK) with cetyltrimethylammonium chloride (CTAC). The aqueous phase was 0.1 M NaCl. The anesthetics decreased the surface charge density, and the effect paralleled the clinical anesthetic potency. At concentrations that induce surgical stage anesthesia in 50% of the population, these anesthetics reduced the surface charge density by 5%.

Adsorption↗

PubMed1996

Characterization of the cerebral distribution of general anesthetics in vivo by two-dimensional 19F chemical shift imaging.

The distribution of two fluorinated anesthetics, halothane and isoflurane, in rabbit brain was mapped during the course of their uptake using 19F NMR chemical shift imaging techniques. Use of a short phase-encoding time and free induction decay acquisition minimized T2-related signal losses in two-dimensional chemical shift imaging. Localization of the brain and exclusion of surrounding tissues was achieved by the use of a surface coil. The spatial distribution of halothane and isoflurane in the brain was nonuniform and both anesthetics were detected predominantly in the cerebral cortex. During the early stages of uptake, anesthetic concentration in the brain was extremely low, but it continued to increase for several hours with sustained anesthetic delivery. Time-dependent variations in anesthetic concentration were observed in different brain regions.

Anesthetics, Inhalation↗

PubMed2006

A succession of anesthetic endpoints in the Drosophila brain.

General anesthetics abolish behavioral responsiveness in all animals, and in humans this is accompanied by loss of consciousness. Whether similar target mechanisms and behavioral endpoints exist across species remains controversial, although model organisms have been successfully used to study mechanisms of anesthesia. In Drosophila, a number of key mutants have been characterized as hypersensitive or resistant to general anesthetics by behavioral assays. In order to investigate general anesthesia in the Drosophila brain, local field potential (LFP) recordings were made during incremental exposures to isoflurane in wild-type and mutant flies. As in higher animals, general anesthesia in flies was found to involve a succession of distinct endpoints. At low doses, isoflurane uncoupled brain activity from ongoing movement, followed by a sudden attenuation in neural correlates of perception. Average LFP activity in the brain was more gradually attenuated with higher doses, followed by loss of movement behavior. Among mutants, a strong correspondence was found between behavioral and LFP sensitivities, thereby suggesting that LFP phenotypes are proximal to the anesthetic's mechanism of action. Finally, genetic and pharmacological analysis revealed that anesthetic sensitivities in the fly brain are, like other arousal states, influenced by dopaminergic activity. These results suggest that volatile anesthetics such as isoflurane may target the same processes that sustain wakefulness and attention in the brain. LFP correlates of general anesthesia in Drosophila provide a powerful new approach to uncovering the nature of these processes.

Anesthetics, General↗

PubMed1996

Investigations of hypesthesia: using anesthetics to explore relationships between consciousness, learning, and memory.

This paper discusses the ways in which anesthetic agents can be used to investigate the role of awareness in learning and memory. It reviews research into learning during light, subclinical anesthesia, termed hypesthesia. This research suggests that the effects of anesthetics on implicit and explicit memory are roughly comparable, although implicit memory for simple stimuli may resist the effects of very low doses of anesthetic. In addition, this paper reports experimental data demonstrating that long-term retention of information is prevented by doses of anesthetic that are low enough to permit awareness and even shortterm memory of auditory stimuli. Overall, these findings are consistent with the hypothesis (e.g., Caseley-Rondi, 1996) that frontal lobe function is particularly sensitive to anesthetics. They raise theoretical and practical questions about the necessity of consciousness for learning and about interpretation of the evidence for learning during surgery under general anesthesia.

Anesthesia, General↗

PubMed2000

Toward a unified theory of narcosis: brain imaging evidence for a thalamocortical switch as the neurophysiologic basis of anesthetic-induced unconsciousness.

A unifying theory of general anesthetic-induced unconsciousness must explain the common mechanism through which various anesthetic agents produce unconsciousness. Functional-brain-imaging data obtained from 11 volunteers during general anesthesia showed specific suppression of regional thalamic and midbrain reticular formation activity across two different commonly used volatile agents. These findings are discussed in relation to findings from sleep neurophysiology and the implications of this work for consciousness research. It is hypothesized that the essential common neurophysiologic mechanism underlying anesthetic-induced unconsciousness is, as with sleep-induced unconsciousness, a hyperpolarization block of thalamocortical neurons. A model of anesthetic-induced unconsciousness is introduced to explain how the plethora of effects anesthetics have on cellular functioning ultimately all converge on a single neuroanatomic/neurophysiologic system, thus providing for a unitary physiologic theory of narcosis related to consciousness.

Adolescent↗

PubMed1996

The comparative genotoxicological study of new local anesthetics, 3-(2-alkoxyphenylcarbamoyloxy)quinuclidium chlorides, on Salmonella typhimurium, Saccharromyces cerevisiae, Vicia faba, Hordeum vulgare and Drosophila melanogaster.

Potential gentoxicity of five new local anesthetics, derivatives of phenylcarbamic acid differing in the length of the alkyl chain of the alkoxy substituent, was studied on five test systems. There was a direct relationship with increased toxic effect in bacteria and yeast as a function of the elongation of the alkyl chain of the alkoxy substituents of the phenylcarbamic acid esters. On the other hand, no structure-toxicity relationship was found after application of 3-(2-alkoxyphenylcarbamoyloxy)-quinuclidium chlorides on plants and Drosophila. All anesthetics were nonmutagenic to Salmonella typhimurium strains TA97, TA98, TA100, and TA102 in the absence and in the presence of S9 mix. Pentyloxy and heptyloxy derivatives increased rates of genetic changes in Saccharomyces cerevisiae, mainly revertants at the isoleucine locus. Pentyloxy and hexyloxy derivatives increased the frequency of chromosome aberrations in Vicia faba root-tip meristems. No chlorophyll mutations were detected after treatment of Hordeum vulgare with pentyloxy, hexyloxy and heptyloxy derivatives. No sex-linked recessive lethals were scored in Drosphila melanogaster males. The rates of aneuploids induced in their germ cells were significantly increased after treatment with butoxy and octyloxy derivatives. However, the local toxic and genotoxic effects of test anesthetics on the microorganisms of the anesthetized tissues may be of some importance. In particular, the genotoxic effect exhibited in fungi by the heptyloxy derivative, a potent local anesthetic, was remarkable.

Anesthetics, Local↗