Lipid emulsions enhance the norepinephrine-mediated reversal of local anesthetic-induced vasodilation at toxic doses.

PubMed

Lee, Soo Hee; Sung, Hui-Jin; Ok, Seong-Ho; Yu, Jongsun; Choi, Mun-Jeoung; Lim, Jin Soo; Sohn, Ju-Tae

2013-11-01

Intravenous lipid emulsions have been used to treat the systemic toxicity of local anesthetics. The goal of this in vitro study was to examine the effects of lipid emulsions on the norepinephrine-mediated reversal of vasodilation induced by high doses of levobupivacaine, ropivacaine, and mepivacaine in isolated endothelium-denuded rat aorta, and to determine whether such effects are associated with the lipid solubility of local anesthetics. The effects of lipid emulsions (0.30, 0.49, 1.40, and 2.61%) on norepinephrine concentration-responses in high-dose local anesthetic (6×10(-4) M levobupivacaine, 2×10(-3) M ropivacaine, and 7×10(-3) M mepivacaine)-induced vasodilation of isolated aorta precontracted with 60 mM KCl were assessed. The effects of lipid emulsions on local anesthetic- and diltiazem-induced vasodilation in isolated aorta precontracted with phenylephrine were also assessed. Lipid emulsions (0.30%) enhanced norepinephrine-induced contraction in levobupivacaine-induced vasodilation, whereas 1.40 and 2.61% lipid emulsions enhanced norepinephrine-induced contraction in both ropivacaine- and mepivacaine-induced vasodilation, respectively. Lipid emulsions (0.20, 0.49 and 1.40%) inhibited vasodilation induced by levobupivacaine and ropivacaine, whereas 1.40 and 2.61% lipid emulsions slightly attenuated mepivacaine (3×10(-3) M)-induced vasodilation. In addition, lipid emulsions attenuated diltiazem-induced vasodilation. Lipid emulsions enhanced norepinephrine-induced contraction in endothelium-denuded aorta without pretreatment with local anesthetics. Taken together, these results suggest that lipid emulsions enhance the norepinephrine-mediated reversal of local anesthetic-induced vasodilation at toxic anesthetic doses and inhibit local anesthetic-induced vasodilation in a manner correlated with the lipid solubility of a particular local anesthetic.

Randomized clinical trial of local anesthetic versus a combination of local anesthetic with self-hypnosis in the management of pediatric procedure-related pain.

PubMed

Liossi, Christina; White, Paul; Hatira, Popi

2006-05-01

A prospective controlled trial was conducted to compare the efficacy of an analgesic cream (eutectic mixture of local anesthetics, or EMLA) with a combination of EMLA with hypnosis in the relief of lumbar puncture-induced pain and anxiety in 45 pediatric cancer patients (age 6-16 years). The study also explored whether young patients can be taught and can use hypnosis independently as well as whether the therapeutic benefit depends on hypnotizability. Patients were randomized to 1 of 3 groups: local anesthetic, local anesthetic plus hypnosis, and local anesthetic plus attention. Results confirmed that patients in the local anesthetic plus hypnosis group reported less anticipatory anxiety and less procedure-related pain and anxiety and that they were rated as demonstrating less behavioral distress during the procedure. The level of hypnotizability was significantly associated with the magnitude of treatment benefit, and this benefit was maintained when patients used hypnosis independently. 2006 APA, all rights reserved

21 CFR 346.10 - Local anesthetic active ingredients.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Local anesthetic active ingredients. 346.10... (CONTINUED) DRUGS FOR HUMAN USE ANORECTAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 346.10 Local anesthetic active ingredients. The active ingredient of the product consists of any of...

21 CFR 346.10 - Local anesthetic active ingredients.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Local anesthetic active ingredients. 346.10... (CONTINUED) DRUGS FOR HUMAN USE ANORECTAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 346.10 Local anesthetic active ingredients. The active ingredient of the product consists of any of...

21 CFR 346.10 - Local anesthetic active ingredients.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Local anesthetic active ingredients. 346.10... (CONTINUED) DRUGS FOR HUMAN USE ANORECTAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Active Ingredients § 346.10 Local anesthetic active ingredients. The active ingredient of the product consists of any of...

21 CFR 346.10 - Local anesthetic active ingredients.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Local anesthetic active ingredients. 346.10 Section 346.10 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... § 346.10 Local anesthetic active ingredients. The active ingredient of the product consists of any of...

21 CFR 346.10 - Local anesthetic active ingredients.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Local anesthetic active ingredients. 346.10 Section 346.10 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... § 346.10 Local anesthetic active ingredients. The active ingredient of the product consists of any of...

Interaction of Local Anesthetics with Biomembranes Consisting of Phospholipids and Cholesterol: Mechanistic and Clinical Implications for Anesthetic and Cardiotoxic Effects

PubMed Central

2013-01-01

Despite a long history in medical and dental application, the molecular mechanism and precise site of action are still arguable for local anesthetics. Their effects are considered to be induced by acting on functional proteins, on membrane lipids, or on both. Local anesthetics primarily interact with sodium channels embedded in cell membranes to reduce the excitability of nerve cells and cardiomyocytes or produce a malfunction of the cardiovascular system. However, the membrane protein-interacting theory cannot explain all of the pharmacological and toxicological features of local anesthetics. The administered drug molecules must diffuse through the lipid barriers of nerve sheaths and penetrate into or across the lipid bilayers of cell membranes to reach the acting site on transmembrane proteins. Amphiphilic local anesthetics interact hydrophobically and electrostatically with lipid bilayers and modify their physicochemical property, with the direct inhibition of membrane functions, and with the resultant alteration of the membrane lipid environments surrounding transmembrane proteins and the subsequent protein conformational change, leading to the inhibition of channel functions. We review recent studies on the interaction of local anesthetics with biomembranes consisting of phospholipids and cholesterol. Understanding the membrane interactivity of local anesthetics would provide novel insights into their anesthetic and cardiotoxic effects. PMID:24174934

Clinical concentrations of chemically diverse general anesthetics minimally affect lipid bilayer properties.

PubMed

Herold, Karl F; Sanford, R Lea; Lee, William; Andersen, Olaf S; Hemmings, Hugh C

2017-03-21

General anesthetics have revolutionized medicine by facilitating invasive procedures, and have thus become essential drugs. However, detailed understanding of their molecular mechanisms remains elusive. A mechanism proposed over a century ago involving unspecified interactions with the lipid bilayer known as the unitary lipid-based hypothesis of anesthetic action, has been challenged by evidence for direct anesthetic interactions with a range of proteins, including transmembrane ion channels. Anesthetic concentrations in the membrane are high (10-100 mM), however, and there is no experimental evidence ruling out a role for the lipid bilayer in their ion channel effects. A recent hypothesis proposes that anesthetic-induced changes in ion channel function result from changes in bilayer lateral pressure that arise from partitioning of anesthetics into the bilayer. We examined the effects of a broad range of chemically diverse general anesthetics and related nonanesthetics on lipid bilayer properties using an established fluorescence assay that senses drug-induced changes in lipid bilayer properties. None of the compounds tested altered bilayer properties sufficiently to produce meaningful changes in ion channel function at clinically relevant concentrations. Even supra-anesthetic concentrations caused minimal bilayer effects, although much higher (toxic) concentrations of certain anesthetic agents did alter lipid bilayer properties. We conclude that general anesthetics have minimal effects on bilayer properties at clinically relevant concentrations, indicating that anesthetic effects on ion channel function are not bilayer-mediated but rather involve direct protein interactions.

Clinical concentrations of chemically diverse general anesthetics minimally affect lipid bilayer properties

PubMed Central

Herold, Karl F.; Sanford, R. Lea; Lee, William; Andersen, Olaf S.; Hemmings, Hugh C.

2017-01-01

General anesthetics have revolutionized medicine by facilitating invasive procedures, and have thus become essential drugs. However, detailed understanding of their molecular mechanisms remains elusive. A mechanism proposed over a century ago involving unspecified interactions with the lipid bilayer known as the unitary lipid-based hypothesis of anesthetic action, has been challenged by evidence for direct anesthetic interactions with a range of proteins, including transmembrane ion channels. Anesthetic concentrations in the membrane are high (10–100 mM), however, and there is no experimental evidence ruling out a role for the lipid bilayer in their ion channel effects. A recent hypothesis proposes that anesthetic-induced changes in ion channel function result from changes in bilayer lateral pressure that arise from partitioning of anesthetics into the bilayer. We examined the effects of a broad range of chemically diverse general anesthetics and related nonanesthetics on lipid bilayer properties using an established fluorescence assay that senses drug-induced changes in lipid bilayer properties. None of the compounds tested altered bilayer properties sufficiently to produce meaningful changes in ion channel function at clinically relevant concentrations. Even supra-anesthetic concentrations caused minimal bilayer effects, although much higher (toxic) concentrations of certain anesthetic agents did alter lipid bilayer properties. We conclude that general anesthetics have minimal effects on bilayer properties at clinically relevant concentrations, indicating that anesthetic effects on ion channel function are not bilayer-mediated but rather involve direct protein interactions. PMID:28265069

Occurrence of paresthesia after dental local anesthetic administration in the United States.

PubMed

Garisto, Gabriella A; Gaffen, Andrew S; Lawrence, Herenia P; Tenenbaum, Howard C; Haas, Daniel A

2010-07-01

Several studies have suggested that the likelihood of paresthesia may depend on the local anesthetic used. The purpose of this study was to determine if the type of local anesthetic administered had any effect on reports of paresthesia in dentistry in the United States. The authors obtained reports of paresthesia involving dental local anesthetics during the period from November 1997 through August 2008 from the U.S. Food and Drug Administration Adverse Event Reporting System. They used chi(2) analysis to compare expected frequencies, on the basis of U.S. local anesthetic sales data, with observed reports of oral paresthesia. During the study period, 248 cases of paresthesia occurring after dental procedures were reported. Most cases (94.5 percent) involved mandibular nerve block. The lingual nerve was affected in 89.0 percent of cases. Reports involving 4 percent prilocaine and 4 percent articaine were 7.3 and 3.6 times, respectively, greater than expected (chi(2), P < .0001) on the basis of local anesthetic use by U.S. dentists. These data suggest that paresthesia occurs more commonly after use of 4 percent local anesthetic formulations. These findings are consistent with those reported in a number of studies from other countries. Until further research indicates otherwise, dentists should consider these results when assessing the risks and benefits of using 4 percent local anesthetics for mandibular block anesthesia.

Preventive Analgesia by Local Anesthetics: The Reduction of Postoperative Pain by Peripheral Nerve Blocks and Intravenous Drugs

PubMed Central

Barreveld, Antje; Witte, Jürgen; Chahal, Harkirat; Durieux, Marcel E.; Strichartz, Gary

2012-01-01

The use of local anesthetics to reduce acute postoperative pain has a long history, but recent reports have not been systematically reviewed. In addition, the need to include only those clinical studies that meet minimum standards for randomization and blinding must be adhered to. In this review we have applied stringent clinical study design standards to identify publications on the use of perioperative local anesthetics. We first examined several types of peripheral nerve blocks, covering a variety of surgical procedures, and second, for effects of intentionally administered IV local anesthetic (lidocaine) for suppression of postoperative pain. Thirdly, we have examined publications in which vascular concentrations of local anesthetics were measured at different times after peripheral nerve block procedures, noting the incidence when those levels reached ones achieved during intentional IV administration. Importantly, the very large number of studies using neuraxial blockade techniques (epidural, spinal) has not been included in this review but will be dealt with separately in a later review. The overall results showed a strongly positive effect of local anesthetics, by either route, for suppressing postoperative pain scores and analgesic (opiate) consumption. In only a few situations were the effects equivocal. Enhanced effectiveness with the addition of adjuvants was not uniformly apparent. The differential benefits between drug delivery before, during, or immediately after a surgical procedure are not obvious, and a general conclusion is that the significant antihyperalgesic effects occur when the local anesthetic is present during the acute postoperative period, and its presence during surgery is not essential for this action. PMID:23408672

Local anesthetic systemic toxicity: update on mechanisms and treatment.

PubMed

Wolfe, John W; Butterworth, John F

2011-10-01

With increases in use of regional anesthesia, local anesthetic systemic toxicity (LAST) has been a topic of interest and debate. Despite many years of research, the exact cause and best treatment of LAST (particularly local anesthetic cardiotoxicity) remain unclear. This review will summarize what is known and what remains uncertain about LAST and its treatment, including information published in the past 12-18 months. Several authorities, including the American Society of Regional Anesthesia and Pain Medicine, have published guidelines on prevention and treatment of LAST. Experimental data continue to add to better understanding of LAST and its treatment. The data are not entirely consistent, but themes include continued evidence to support the ideas that LAST cardiotoxicity occurs primarily at sodium channels, lipid emulsion is a reasonably well tolerated and effective treatment, and there may be qualitative differences in cardiotoxicity caused by low and high-potency local anesthetics. Regarding mechanism(s) of LAST, the evidence remains mixed, but it is likely that local anesthetic cardiotoxicity primarily arises from a blockade of sodium channels. As for treatment, in addition to ventilation, oxygenation, and chest compressions, lipid emulsion therapy should be a primary element in the treatment of cardiovascular LAST. The use of epinephrine and vasopressin should be tailored to specifics of an episode of LAST, and doses should be kept as low as possible while still achieving the desired effects.

An Uncommon Complication With Use of Topical Local Anesthetic Agents: Methemoglobinemia.

PubMed

Panikkath, Ragesh; Panikkath, Deepa; Wischmeyer, Jason

Although the use of topical local anesthetics is generally safe, several potentially fatal complications have been reported. Methemoglobinemia is a rare but potentially fatal complication. Methemoglobin is a naturally occurring oxidized metabolite of hemoglobin, and physiologic levels (<1%) are normal. Methemoglobinemia can be congenital or acquired. Several drugs including topical anesthetic agents like benzocaine can induce this condition. Sudden appearance of cyanosis, with a disproportionately better oxygen saturation of 85% after use of local anesthetics can be a helpful for diagnosis.

The effects of local anesthetics on postoperative pain.

PubMed

Roberge, C W; McEwen, M

1998-12-01

This study was performed to determine if intraoperative local anesthesia improved control of postoperative pain after inguinal herniorrhaphy and to compare the effects of two commonly used local anesthetics on pain management. The Gate Control Theory of Pain formed the theoretical basis for this study. A retrospective nonexperimental study in an ex post facto design was used. Data were collected from 1990 through 1997 on 120 patient charts. The use of local anesthetic intraoperatively significantly decreased patients' lengths of stay postoperatively (P = 0.00) and need for postoperative narcotics (P = 0.00). Bupivacaine was found to be superior to lidocaine in decreasing the need for postoperative narcotic analgesia. Researchers concluded that many patients would benefit from intraoperative injection of local anesthesia. This information can affect patient care outcomes through decreasing recovery time, reducing postoperative pain, and reducing health care costs.

Local anesthetics disrupt energetic coupling between the voltage-sensing segments of a sodium channel.

PubMed

Muroi, Yukiko; Chanda, Baron

2009-01-01

Local anesthetics block sodium channels in a state-dependent fashion, binding with higher affinity to open and/or inactivated states. Gating current measurements show that local anesthetics immobilize a fraction of the gating charge, suggesting that the movement of voltage sensors is modified when a local anesthetic binds to the pore of the sodium channel. Here, using voltage clamp fluorescence measurements, we provide a quantitative description of the effect of local anesthetics on the steady-state behavior of the voltage-sensing segments of a sodium channel. Lidocaine and QX-314 shifted the midpoints of the fluorescence-voltage (F-V) curves of S4 domain III in the hyperpolarizing direction by 57 and 65 mV, respectively. A single mutation in the S6 of domain IV (F1579A), a site critical for local anesthetic block, abolished the effect of QX-314 on the voltage sensor of domain III. Both local anesthetics modestly shifted the F-V relationships of S4 domain IV toward hyperpolarized potentials. In contrast, the F-V curve of the S4 domain I was shifted by 11 mV in the depolarizing direction upon QX-314 binding. These antagonistic effects of the local anesthetic indicate that the drug modifies the coupling between the voltage-sensing domains of the sodium channel. Our findings suggest a novel role of local anesthetics in modulating the gating apparatus of the sodium channel.

Membrane permeable local anesthetics modulate NaV1.5 mechanosensitivity

PubMed Central

Beyder, Arthur; Strege, Peter R.; Bernard, Cheryl; Farrugia, Gianrico

2012-01-01

Voltage-gated sodium selective ion channel NaV1.5 is expressed in the heart and the gastrointestinal tract, which are mechanically active organs. NaV1.5 is mechanosensitive at stimuli that gate other mechanosensitive ion channels. Local anesthetic and antiarrhythmic drugs act upon NaV1.5 to modulate activity by multiple mechanisms. This study examined whether NaV1.5 mechanosensitivity is modulated by local anesthetics. NaV1.5 channels wereexpressed in HEK-293 cells, and mechanosensitivity was tested in cell-attached and excised inside-out configurations. Using a novel protocol with paired voltage ladders and short pressure pulses, negative patch pressure (-30 mmHg) in both configurations produced a hyperpolarizing shift in the half-point of the voltage-dependence of activation (V1/2a) and inactivation (V1/2i) by about -10 mV. Lidocaine (50 µM) inhibited the pressure-induced shift of V1/2a but not V1/2i. Lidocaine inhibited the tonic increase in pressure-induced peak current in a use-dependence protocol, but it did not otherwise affect use-dependent block. The local anesthetic benzocaine, which does not show use-dependent block, also effectively blocked a pressure-induced shift in V1/2a. Lidocaine inhibited mechanosensitivity in NaV1.5 at the local anesthetic binding site mutated (F1760A). However, a membrane impermeable lidocaine analog QX-314 did not affect mechanosensitivity of F1760A NaV1.5 when applied from either side of the membrane. These data suggest that the mechanism of lidocaine inhibition of the pressure-induced shift in the half-point of voltage-dependence of activation is separate from the mechanisms of use-dependent block. Modulation of NaV1.5 mechanosensitivity by the membrane permeable local anesthetics may require hydrophobic access and may involve membrane-protein interactions. PMID:22874086

Computer simulations of local anesthetic mechanisms: Quantum chemical investigation of procaine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, Jeremy C; Bondar, A.N.; Suhai, Sandor

2007-02-01

A description at the atomic level of detail of the interaction between local anesthetics, lipid membranes and membrane proteins, is essential for understanding the mechanism of local anesthesia. The importance of performing computer simulations to decipher the mechanism of local anesthesia is discussed here in the context of the current status of understanding of the local anesthetics action. As a first step towards accurate simulations of the interaction between local anesthetics, proteins, lipid and water molecules, here we use quantum mechanical methods to assess the charge distribution and structural properties of procaine in the presence and in the absence ofmore » water molecules. The calculations indicate that, in the absence of hydrogen-bonding water molecules, protonated procaine strongly prefers a compact structure enabled by intramolecular hydrogen bonding. In the presence of water molecules the torsional energy pro?le of procaine is modified, and hydrogen bonding to water molecules is favored relative to intra-molecular hydrogen bonding.« less

Lipid Emulsion in Treatment of Local Anesthetic Toxicity.

PubMed

Collins, Shawn; Neubrander, Judy; Vorst, Zachary; Sheffield, Brad

2015-08-01

Epidural, spinal, regional, local, and intravenous administration of local anesthetics (LAs) is a cornerstone of anesthetic practice. LA toxicity is a grave consequence that is of great significance to anesthesia providers. Outcomes of LA toxicity range from inconvenient symptoms such as tinnitus, twitching, and hypotension to seizures; cardiovascular or respiratory collapse; and death. Lipid emulsion has emerged as a potential "magic bullet" in treating LA toxicity. This literature review provides background information and proposed mechanisms of action for LAs and lipid emulsion as well as animal experiments and a case report that speak to the effectiveness of lipid emulsion in the face of LA toxicity. Copyright © 2015 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.

Local anesthetic lidocaine delivery system: chitosan and hyaluronic acid-modified layer-by-layer lipid nanoparticles.

PubMed

Zhang, Laizhu; Wang, Jianguo; Chi, Huimin; Wang, Shilei

2016-11-01

Transdermal local anesthesia is one of the most applied strategies to avoid systemic adverse effects; there is an appealing need for a prolonged local anesthetic that would provide better bioavailability and longer pain relief with a single administration. Layer-by-layer (LBL) technique was used in this study to explore a nanosized drug delivery system for local anesthetic therapy. LBL-coated lidocaine-loaded nanostructured lipid nanoparticles (LBL-LA/NLCs) were prepared and characterized in terms of particle size (PS), zeta potential, drug encapsulation efficiency (EE), in vitro skin permeation and in vivo local anesthetic studies. Evaluation of the in vitro skin permeation and in vivo anesthesia effect illustrated that LBL-LA/NLCs can enhance and prolong the anesthetic effect of LA. LBL-LA/NLCs could function as a promising drug delivery strategy for overcoming the barrier function of the skin and could deliver anesthetic through the skin with sustained release behavior for local anesthetic therapy.

History of T-cain: a local anesthetic developed and manufactured in Japan.

PubMed

Tobe, Masaru; Saito, Shigeru

2015-10-01

In many anesthesia textbooks written in English, lidocaine, tetracaine, bupivacaine, ropivacaine, and chloroprocaine are listed as useful local anesthetics for spinal anesthesia. In contrast, T-cain is not included in these lists, even though it has been reported to be suitable for spinal anesthesia in Japan. T-cain was developed as a local anesthetic in the early 1940s by Teikoku Kagaku Sangyo Inc. in Itami, Japan, by replacing a methyl group on tetracaine (Pantocaine(®)) with an ethyl group. T-cain was clinically approved for topical use in Japan in November 1949, and a mixture of dibucaine and T-cain (Neo-Percamin S(®)) was approved for spinal use in May 1950. Simply because of a lack of foreign marketing strategy, T-cain has never attracted global attention as a local anesthetic. However, in Japan, T-cain has been used topically or intrathecally (as Neo-Percamin S(®)) for more than 60 years. Other than the side effects generally known for all local anesthetics, serious side effects have not been reported for T-cain. In fact, several articles have reported that T-cain decreases the neurotoxicity of dibucaine. In this historical review, the characteristics of T-cain and its rise to become a major spinal anesthetic in Japan are discussed.

Computer-controlled local anesthetic delivery for painless anesthesia: a literature review

PubMed Central

Kwak, Eun-Jung; Pang, Nan-Sim; Cho, Jin-Hyung; Jung, Bock-Young; Kim, Kee-Deog

2016-01-01

Local anesthesia is administered to reduce pain during dental treatments, but may itself cause pain and contribute to increased dental fear. Computer-controlled local anesthetic delivery (CCLAD) is one the method to reduce patient pain during local anesthesia; it is a device that slowly administers anesthetics by using a computerized device to control the injection speed. This literature review aims to provide an objective assessment of the usefulness of CCLAD for controlling pain by reviewing papers published to date that have used CCLAD. PMID:28879299

Uses and Doses of Local Anesthetics in Fish, Amphibians, and Reptiles.

PubMed

Chatigny, Frederic; Kamunde, Collins; Creighton, Catherine M; Stevens, E Don

2017-05-01

Local anesthetics are an integral part of routine pain management in mammals, yet their use is relatively limited in fish, amphibians and reptiles. These animals frequently undergo potentially painful surgical procedures and therefore could possibly benefit from those drugs. Some recommendations are currently available in the literature concerning analgesic use in these animals. However the pharmacological properties, safety and often efficacy of local anesthetic drugs have not been investigated yet in fish, amphibians, or reptiles. This review compiled current information concerning the use of those agents in fish, reptiles and amphibians to help clinicians make an informed decision as to which dose and drug to use. The resulting literature search showed that the literature concerning use of local analgesics in fish and amphibians is very limited while the literature for reptiles is more extensive. We found few experimental studies evaluating the efficacy of local anesthetics. Further studies would provide additional information for developing guidelines to improve the welfare of fish, amphibians and reptiles.

Uses and Doses of Local Anesthetics in Fish, Amphibians, and Reptiles

PubMed Central

Chatigny, Frederic; Kamunde, Collins; Creighton, Catherine M; Stevens, E Don

2017-01-01

Local anesthetics are an integral part of routine pain management in mammals, yet their use is relatively limited in fish, amphibians and reptiles. These animals frequently undergo potentially painful surgical procedures and therefore could possibly benefit from those drugs. Some recommendations are currently available in the literature concerning analgesic use in these animals. However the pharmacological properties, safety and often efficacy of local anesthetic drugs have not been investigated yet in fish, amphibians, or reptiles. This review compiled current information concerning the use of those agents in fish, reptiles and amphibians to help clinicians make an informed decision as to which dose and drug to use. The resulting literature search showed that the literature concerning use of local analgesics in fish and amphibians is very limited while the literature for reptiles is more extensive. We found few experimental studies evaluating the efficacy of local anesthetics. Further studies would provide additional information for developing guidelines to improve the welfare of fish, amphibians and reptiles. PMID:28535859

Assessment of the densities of local anesthetics and their combination with adjuvants: an experimental study.

PubMed

Imbelloni, Luiz Eduardo; Moreira, Adriano Dias; Gaspar, Flávia Cunha; Gouveia, Marildo A; Cordeiro, José Antônio

2009-01-01

The relative density of a local anesthetic in relation to that of the cerebrospinal fluid (CSF) at 37 degrees C is one of the most important physical properties that affect the level of analgesia obtained after the subarachnoid administration of the drug. The objective of this study was to determine the density of local anesthetic solutions, with and without glucose, and the combination of the local anesthetic with adjuvants at 20 degrees C, 25 degrees C, and 37 degrees C. The density (g.mL(-1)) was determined by using a DMA 450 densimeter with a sensitivity of +/- 0.00001 g.mL(-1). The densities, and variations, according to the temperature were obtained for all local anesthetics and their combination with opioids at 20 degrees C, 25 degrees C, and 37 degrees C. The solution is hyperbaric if its density exceeds 1.00099, hypobaric when its density is lower than 1.00019, and isobaric when its density is greater than 1.00019 and lower than 1.00099. The densities of both local anesthetics and adjuvants decrease with the increase in temperature. At 37 degrees C, all glucose-containing solutions are hyperbaric. In the absence of glucose, all solutions are hypobaric. At 37 degrees C, morphine, fentanyl, sufentanil, and clonidine are hypobaric. The densities of local anesthetics and adjuvants decrease with the increase in temperature and increase when glucose is added. The knowledge of the relative density helps select the most adequate local anesthetic to be administered in the subarachnoid space.

Additives to local anesthetics for peripheral nerve blocks: Evidence, limitations, and recommendations.

PubMed

Bailard, Neil S; Ortiz, Jaime; Flores, Roland A

2014-03-01

The therapeutic rationale, clinical effectiveness, and potential adverse effects of medications used in combination with local anesthetics for peripheral nerve block therapy are reviewed. A wide range of agents have been tested as adjuncts to peripheral nerve blocks, which are commonly performed for regional anesthesia during or after hand or arm surgery, neck or spine surgery, and other procedures. Studies to determine the comparative merits of nerve block adjuncts are complicated by the wide variety of coadministered local anesthetics and sites of administration and by the heterogeneity of primary endpoints. Sodium bicarbonate has been shown to speed the onset of mepivacaine nerve blocks but delay the onset of others. Epinephrine has been shown to prolong sensory nerve blockade and delay systemic uptake of local anesthetics, thus reducing the risk of anesthetic toxicity. Tramadol, buprenorphine, dexamethasone, and clonidine appear to be effective additives in some situations. Midazolam, magnesium, dexmedetomidine, and ketamine cannot be routinely recommended as nerve block additives due to a dearth of supportive data, modest efficacy, and (in the case of ketamine) significant adverse effects. Recent studies suggest that administering additives intravenously or intramuscularly can provide many of the benefits of perineural administration while reducing the potential for neurotoxicity, contamination, and other hazards. Some additives to local anesthetics can hasten the onset of nerve block, prolong block duration, or reduce toxicity. On the other hand, poorly selected or unnecessary additives may not have the desired effect and may even expose patients to unnecessary risks.

Local anesthetic infusion pump for pain management following total knee arthroplasty: a meta-analysis.

PubMed

Zhang, Yeying; Lu, Ming; Chang, Cheng

2017-01-23

We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) were to evaluate the effect and safety of local anesthetic infusion pump versus placebo for pain management following total knee arthroplasty (TKA). In September 2016, a systematic computer-based search was conducted in the Pubmed, ISI Web of Knowledge, Embase, Cochrane Database of Systematic Reviews. Randomized controlled trials of patients prepared for primary TKA that compared local anesthetic infusion pump versus placebo for pain management following TKA were retrieved. The primary endpoint was the visual analogue scale (VAS) with rest or mobilization at 24, 48 and 72 h and morphine consumption at 24 and 48 h. The second outcomes are range of motion, length of hospital stay (LOS) and complications (infection, deep venous thrombosis (DVT), prolonged drainage and postoperative nausea and vomiting (PONV)). Seven clinical studies with 587 patients were included and for meta-analysis. Local anesthetic infusion pump are associated with less pain scores with rest or mobilization at 24 and 48 h with significant difference. However, the difference was likely no clinical significance. There were no significant difference between the LOS, the occurrence of DVT, prolonged drainage and PONV. However, local anesthetic infusion pump may be associated with more infection. Based on the current meta-analysis, we found no evidence to support the routine use of local anesthetic infusion pump in the management of acute pain following TKA. More RCTs are still need to identify the pain control effects and optimal dose and speed of local anesthetic pain pump.

Binding of long-lasting local anesthetics to lipid emulsions.

PubMed

Mazoit, Jean-Xavier; Le Guen, Régine; Beloeil, Hélène; Benhamou, Dan

2009-02-01

Rapid infusion of lipid emulsion has been proposed to treat local anesthetic toxicity. The authors wanted to test the buffering properties of two commercially available emulsions made of long- and of long- and medium-chain triglycerides. Using the shake-flask method, the authors measured the solubility and binding of racemic bupivacaine, levobupivacaine, and ropivacaine to diluted Intralipid (Fresenius Kabi, Paris, France) and Medialipide (B-Braun, Boulogne, France). The apparent distribution coefficient expressed as the ratio of mole fraction was 823 +/- 198 and 320 +/- 65 for racemic bupivacaine and levobupivacaine, and ropivacaine, respectively, at 500 mg in the Medialipide/buffer emulsion; and 1,870 +/- 92 and 1,240 +/- 14 for racemic bupivacaine and levobupivacaine, and ropivacaine, respectively, in the Intralipid/buffer emulsion. Decreasing the pH from 7.40 to 7.00 of the Medialipide/buffer emulsion led to a decrease in ratio of molar concentration from 121 +/- 3.8 to 46 +/- 2.8 for bupivacaine, and to a lesser extent from 51 +/- 4.0 to 31 +/- 1.6 for ropivacaine. The capacity of the 1% emulsions was 871 and 2,200 microM for the 1% Medialipide and Intralipid emulsions, respectively. The dissociation constant was 818 and 2,120 microM for racemic bupivacaine and levobupivacaine, and ropivacaine, respectively. Increasing the temperature from 20 to 37 degrees C led to a greater increase in affinity for ropivacaine (55%) than for bupivacaine (27%). When the pH of the buffer was decreased from 7.40 to 7.00, the affinity was decreased by a factor of 1.68, similar for both anesthetics. The solubility of long-acting local anesthetics in lipid emulsions and the high capacity of binding of these emulsions most probably explain their clinical efficacy in case of toxicity. The long-chain triglyceride emulsion Intralipid appears to be about 2.5 times more efficacious than the 50/50 medium-chain/long-chain Medialipide emulsion. Also, because of their higher hydrophobicity

Concentrations of anesthetics across the water-membrane interface; the Meyer-Overton hypothesis revisited

NASA Technical Reports Server (NTRS)

Pohorille, A.; Wilson, M. A.; New, M. H.; Chipot, C.

1998-01-01

The free energies of transferring a variety of anesthetic and nonanesthetic compounds across water-oil and water-membrane interfaces were obtained using computer simulations. Anesthetics exhibit greatly enhanced concentrations at these interfaces, compared to nonanesthetics. The substitution of the interfacial solubilites of the anesthetics for their bulk lipid solubilities in the Meyer-Overton relation, was found to give a better correlation, indicating that the potency of an anesthetic is directly proportional to its solubility at the interface.

On Beyond Lidocaine: Reconsidering Local Anesthetics in Tumescent Liposuction-A Critical Review.

PubMed

Hsia, Henry C

2016-02-01

The use of tumescent solution in liposuction is now considered standard of care; however, much debate still exists regarding its ideal components, especially surrounding the inclusion of local anesthetics. This article reviews the discussion regarding the use of local anesthetics in tumescent liposuction and how it may evolve in the future. The need for local anesthetic additives in tumescent liposuction has been questioned, and the use of longer-acting agents discouraged; however, increasing number of reports in recent years have described the increasingly widespread use of tumescent anesthesia where a wetting solution is infiltrated to achieve anesthesia in an operative field for procedures other than liposuction. More high-level evidence, such as randomized controlled clinical trials, will be required; however, it should be possible to develop a useful standardized algorithm that can guide surgeons to optimize patient safety as well as patient experience.

Local anesthetics: special considerations in endodontics.

PubMed

Jeske, Arthur H

2003-03-01

Local anesthetics are essential for successful endodontic treatment, and their pharmacologic characteristics have special implications for the treatment of painful, chronically-inflamed or necrotic teeth. Their dosages must be limited to prevent toxicity, which may be enhanced by the coadministration of sedative agents or drugs which affect hepatic drug metabolism. Endodontic patients with established central and peripheral sensitization represent special challenges for pain control, since morphogenetic changes resulting from neurogenic inflammation can render pain fibers more resistant to local anesthesia. The use of vasconstrictors with conventional and alternative injection techniques, e.g., intraosseous injections, are necessary to prolong the duration of action of local anesthesia but can place patients with cardiovascular disease at some risk. An appreciation of all of these aspects of local anesthesia in endodontics will better prepare the operator for predictably safe and effective patient care.

Hypnosis control based on the minimum concentration of anesthetic drug for maintaining appropriate hypnosis.

PubMed

Furutani, Eiko; Nishigaki, Yuki; Kanda, Chiaki; Takeda, Toshihiro; Shirakami, Gotaro

2013-01-01

This paper proposes a novel hypnosis control method using Auditory Evoked Potential Index (aepEX) as a hypnosis index. In order to avoid side effects of an anesthetic drug, it is desirable to reduce the amount of an anesthetic drug during surgery. For this purpose many studies of hypnosis control systems have been done. Most of them use Bispectral Index (BIS), another hypnosis index, but it has problems of dependence on anesthetic drugs and nonsmooth change near some particular values. On the other hand, aepEX has an ability of clear distinction between patient consciousness and unconsciousness and independence of anesthetic drugs. The control method proposed in this paper consists of two elements: estimating the minimum effect-site concentration for maintaining appropriate hypnosis and adjusting infusion rate of an anesthetic drug, propofol, using model predictive control. The minimum effect-site concentration is estimated utilizing the property of aepEX pharmacodynamics. The infusion rate of propofol is adjusted so that effect-site concentration of propofol may be kept near and always above the minimum effect-site concentration. Simulation results of hypnosis control using the proposed method show that the minimum concentration can be estimated appropriately and that the proposed control method can maintain hypnosis adequately and reduce the total infusion amount of propofol.

Inhibition of Kv7/M Channel Currents by the Local Anesthetic Chloroprocaine.

PubMed

Zhang, Fan; Cheng, Yanxin; Li, Hong; Jia, Qingzhong; Zhang, Hailin; Zhao, Senming

2015-01-01

Chloroprocaine is a local ester anesthetic, producing excellent sensory block in clinical use. The Kv7/M potassium channel plays an important role in the control of neuronal excitability. In this study, we investigated the effects of the local anesthetic chloroprocaine on Kv7/M channels as well as the effect of retigabine on chloroprocaine-induced seizures. A perforated whole-cell patch technique was used to record Kv7 currents from HEK293 cells and M-type currents from rat dorsal root ganglion (DRG) neurons. Chloroprocaine produced a number of effects on Kv7.2/Kv7.3 currents, including a lowering of current amplitudes, a rightward shift in the voltage-dependent activation curves, and a slowing of channel activation. Chloroprocaine had a more selective inhibitory effect on the homomeric Kv7.3 and heteromeric Kv7.2/Kv7.3 channels than on the homomeric Kv7.2 channel. Chloroprocaine also inhibited native M channel currents and induced a depolarization of the DRG neuron membrane potential. Taken together, the findings indicate that chloroprocaine concentration dependently inhibited Kv7/M channel currents. © 2015 S. Karger AG, Basel.

The efficacy of eutectic mixture of local anesthetics as a topical anesthetic agent used for dental procedures: A brief review

PubMed Central

Daneshkazemi, Alireza; Abrisham, Seyyed Mohammad; Daneshkazemi, Pedram; Davoudi, Amin

2016-01-01

Dental pain management is one of the most critical aspects of modern dentistry which might affect patient's quality of life. Several methods are suggested to provide a painless situation for patients. Desensitization of the oral site using topical anesthetics is one of those methods. The improvements of topical anesthetic agents are probably one of the most important advances in dental science in the past 100 years. Most of them are safe and can be applied on oral mucosa with minimal irritation and allergic reactions. At present, these agents are various with different potent and indications. Eutectic mixture of local anesthetics (EMLA) (lidocaine + prilocaine) is a commercial anesthetic agent which has got acceptance among dental clinicians. This article provides a brief review about the efficacy of EMLA as a topical anesthetic agent when used during dental procedures. PMID:27746520

The efficacy of eutectic mixture of local anesthetics as a topical anesthetic agent used for dental procedures: A brief review.

PubMed

Daneshkazemi, Alireza; Abrisham, Seyyed Mohammad; Daneshkazemi, Pedram; Davoudi, Amin

2016-01-01

Dental pain management is one of the most critical aspects of modern dentistry which might affect patient's quality of life. Several methods are suggested to provide a painless situation for patients. Desensitization of the oral site using topical anesthetics is one of those methods. The improvements of topical anesthetic agents are probably one of the most important advances in dental science in the past 100 years. Most of them are safe and can be applied on oral mucosa with minimal irritation and allergic reactions. At present, these agents are various with different potent and indications. Eutectic mixture of local anesthetics (EMLA) (lidocaine + prilocaine) is a commercial anesthetic agent which has got acceptance among dental clinicians. This article provides a brief review about the efficacy of EMLA as a topical anesthetic agent when used during dental procedures.

[Preemptive local anesthetic infiltration in hallux valgus one-day surgery].

PubMed

Gądek, Artur; Liszka, Henryk

2015-01-01

The surgical treatment of hallux valgus deformity is connected with significant postoperative pain. Spinal and general anesthesia as well as peripheral blocks are successfully used in foot surgery. The purpose of this study was to evaluate the influence of local anesthetic infiltration before hallux valgus one-day surgery on postoperative pain and the need for analgesics. 134 patients underwent chevron or miniinvasive Mitchell-Kramer osteotomy of the first distal metatarsal. After general anesthesia each patient randomly received an infiltration of 7ml of local anesthetic (4 ml of 0.25% bupivacaine and 3 ml of 2% lidocaine) or the same amount of normal saline 15 minutes before the skin incision. Both the patient and the surgeon were blinded. The patient was discharged after approximately 2 hours of observation. 2, 4, 8, 12, 16, 24 and 72 hours after the release of the tourniquet the level of pain was assessed by the visual analogue scale (VAS). Rescue analgesia, side effects and the use of painkillers were noted. Preemptive local anesthetic infiltration significantly decreased pain during the first 24 hours after the surgery. None of the patients from the injected group and 38 from the placebo group received 100 mg of ketoprofen intravenously for rescue analgesia in the first 2 hours after the release of the tourniquet. During the first 24 hours we noted significantly decreased use of 1000 mg of paracetamol and 100 mg mg of ketoprofen orally in the injected group. No systemic adverse effects were noted. One patient from placebo group had allergic rush after use of 100 mg ketoprofen. Preemptive local anesthetic infiltration in one-day hallux valgus surgery significantly decreases postoperative pain. It is safe, efficient and allows fast discharge.

Intrathecal opioids versus epidural local anesthetics for labor analgesia: a meta-analysis.

PubMed

Bucklin, Brenda A; Chestnut, David H; Hawkins, Joy L

2002-01-01

Some anesthesiologists contend that intrathecal opioid administration has advantages over conventional epidural techniques during labor. Randomized clinical trials comparing analgesia and obstetric outcome using single-injection intrathecal opioids versus epidural local anesthetics suggest that intrathecal opioids provide comparable analgesia with few serious side effects. This meta-analysis compared the analgesic efficacy, side effects, and obstetric outcome of single-injection intrathecal opioid techniques versus epidural local anesthetics in laboring women. Relevant clinical studies were identified using electronic and manual searches of the literature covering the period from 1989 to 2000. Searches used the following descriptors: intrathecal analgesia, spinal opioids, epidural analgesia, epidural local anesthetics, and analgesia for labor. Data were extracted from 7 randomized clinical trials comparing analgesic measures, incidence of motor block, pruritus, nausea, hypotension, mode of delivery, and/or Apgar scores. Combined test results indicated comparable analgesic efficacy 15 to 20 minutes after injection with single-injection intrathecal opioid administration. Intrathecal opioid injections were associated with a greater incidence of pruritus (odds ratio, 14.01; 99% confidence interval, 6.9 to 28.3), but there was no difference in the incidence of nausea or in the method of delivery. Published studies suggest that intrathecal opioids provide comparable early labor analgesia when compared with epidural local anesthetics. Intrathecal opioid administration results in a greater incidence of pruritus. The choice of technique does not appear to affect the method of delivery.

Local anesthetic effects of bupivacaine loaded lipid-polymer hybrid nanoparticles: In vitro and in vivo evaluation.

PubMed

Ma, Pengju; Li, Ting; Xing, Huaixin; Wang, Suzhen; Sun, Yingui; Sheng, Xiugui; Wang, Kaiguo

2017-05-01

There is a compelling need for prolonged local anesthetic that would be used for analgesia with a single administration. However, due to the low molecular weight of local anesthetics (LA) (lidocaine, bupivacaine, procaine, dibucaine, etc), they present fast systemic absorption. The aim of the present study was to develop and evaluate bupivacaine lipid-polymer hybrid nanoparticles (BVC LPNs), and compared with BVC loaded PLGA nanoparticles (BVC NPs). Their morphology, particle size, zeta potential and drug loading capacity were evaluated. In vitro release study, stability and cytotoxicity were studied. In vivo evaluation of anesthetic effects was performed on animal models. A facile nanoprecipitation and self-assembly method was optimized to obtain BVC LPNs, composed of PLGA, lecithin and DSPE-PEG 2000 , of ∼175nm particle size. Compared to BVC NPs, BVC LPNs exhibited prolonged in vitro release in phosphate-buffered saline (pH=7.4). Further, BVC LPNs displayed enhanced in vitro stability in 10% FBS and lower cytotoxicity (the concentration of BVC ranging from 1.0μM to 20μM). In addition, BVC LPNs exhibited significantly prolonged analgesic duration. These results demonstrate that the LPNs could function as promising drug delivery system for overcoming the drawbacks of poor stability and rapid drug leakage, and prolonging the anesthetic effect with slight toxicity. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Dexmedetomidine as an adjuvant to local anesthetics in brachial plexus blocks

PubMed Central

Ping, Yongmei; Ye, Qigang; Wang, Wenwei; Ye, Pingke; You, Zhibin

2017-01-01

Abstract Background: Brachial plexus block (BPB) for upper extremity surgery provides superior analgesia, but this advantage is limited by the pharmacological duration of local anesthetics. Dexmedetomidine (DEX) as a local anesthetics adjuvant for BPB has been utilized to prolong the duration of the nerve block in some randomized controlled trials (RCTs) but is far from unanimous in the efficacy and safety of the perineural route. Hence, an updated meta-analysis was conducted to assess the efficacy and safety of DEX as local anesthetic adjuvants on BPB. Methods: A search in electronic databases was conducted to collect the RCTs that investigated the impact of adding DEX to local anesthetics for BPB. Sensory block duration, motor block duration, onset time of sensory and motor block, time to first analgesic request, the common adverse effects were analyzed. Results: Eighteen trails (1014 patients) were included with 515 patients receiving perineural DEX. The addition of DEX prolonged the duration of sensory block (WMD 257 minutes, 95%CI 191.79–322.24, P < 0.001), motor block (WMD 242 minutes, 95%CI 174.94–309.34, P < 0.001), and analgesia (WMD 26 6 minutes, 95%CI 190.75–342.81, P < 0.001). Perineural DEX also increased the risk of bradycardia (OR=8.25, 95%CI 3.95–17.24, P < 0.001), hypotension (OR = 5.62, 95%CI 1.52–20.79, P < 0.01), and somnolence (OR = 19.67, 95%CI 3.94–98.09, P < 0.001). There was a lack of evidence that perineural DEX increased the risk of other adverse events. Conclusions: DEX is a potential anesthetic adjuvant that can facilitate better anesthesia and analgesia when administered in BPB. However, it also increased the risk of bradycardia, hypotension, and somnolence. Further research should focus on the efficacy and safety of the preneural administration of DEX. PMID:28121930

Comparison of local anesthetics for digital nerve blocks: a systematic review.

PubMed

Vinycomb, Toby I; Sahhar, Lukas J

2014-04-01

To evaluate the time to onset of anesthesia, duration of anesthesia, and pain on injection of local anesthetics. A systematic search of the English literature was performed of the Medline, Cochrane Central Register of Controlled Trials, The Allied and Complementary Medicine Database (AMED), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases. The study selection process was adapted from the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement, and 6 articles were complied with the study inclusion criteria. Six studies (335 nerve blocks) were included in our final analysis measuring 6 local anesthetic preparations (lidocaine, lidocaine with epinephrine, bupivacaine, bupivacaine with epinephrine, lidocaine with bupivacaine, and ropivacaine). Lidocaine demonstrated the shortest mean onset of anesthesia (3.1 min) and bupivacaine the longest (7.6 min). Lidocaine also demonstrated the shortest mean duration of anesthesia (1.8 h) and ropivacaine the longest mean duration (21.5 h). Lidocaine with epinephrine demonstrated the least mean pain on injection (26 mm on a visual analog scale) and bupivacaine with epinephrine the most mean pain (53 mm). Lidocaine with epinephrine provides a good short-term anesthesia and may reduce the risk of injury or complication while the finger in still anesthetized. Bupivacaine with lidocaine provides good long-term anesthesia and may reduce the need for postprocedural anesthesia. Ropivacaine likely provides the longest duration of anesthesia but the absence of epinephrine means a tourniquet must be used to create a bloodless field and thus is contraindicated in some procedures such as flexor tendon repairs where active testing may be required. Lidocaine with epinephrine, bupivacaine with epinephrine, and ropivacaine all provide benefits in digital nerve blocks. The surgeon may choose the most appropriate local anesthetic or combination of local anesthetics based on the procedure to be

Comparison of use of an infrared anesthetic gas monitor and refractometry for measurement of anesthetic agent concentrations.

PubMed

Ambrisko, Tamas D; Klide, Alan M

2011-10-01

To assess agreement between anesthetic agent concentrations measured by use of an infrared anesthetic gas monitor (IAGM) and refractometry. SAMPLE-4 IAGMs of the same type and 1 refractometer. Mixtures of oxygen and isoflurane, sevoflurane, desflurane, or N(2)O were used. Agent volume percent was measured simultaneously with 4 IAGMs and a refractometer at the common gas outlet. Measurements obtained with each of the 4 IAGMs were compared with the corresponding refractometer measurements via the Bland-Altman method. Similarly, Bland-Altman plots were also created with either IAGM or refractometer measurements and desflurane vaporizer dial settings. Bias ± 2 SD for comparisons of IAGM and refractometer measurements was as follows: isoflurane, -0.03 ± 0.18 volume percent; sevoflurane, -0.19 ± 0.23 volume percent; desflurane, 0.43 ± 1.22 volume percent; and N(2)O, -0.21 ± 1.88 volume percent. Bland-Altman plots comparing IAGM and refractometer measurements revealed nonlinear relationships for sevoflurane, desflurane, and N(2)O. Desflurane measurements were notably affected; bias ± limits of agreement (2 SD) were small (0.1 ± 0.22 volume percent) at < 12 volume percent, but both bias and limits of agreement increased at higher concentrations. Because IAGM measurements did not but refractometer measurements did agree with the desflurane vaporizer dial settings, infrared measurement technology was a suspected cause of the nonlinear relationships. Given that the assumption of linearity is a cornerstone of anesthetic monitor calibration, this assumption should be confirmed before anesthetic monitors are used in experiments.

Ice Reduces Needle-Stick Pain Associated With Local Anesthetic Injection

PubMed Central

Mahshidfar, Babak; Cheraghi Shevi, Salimeh; Abbasi, Mohsen; Kasnavieh, Mohammad Hosseini; Rezai, Mahdi; Zavereh, Mina; Mosaddegh, Reza

2016-01-01

Background Local anesthetic injections are widely used in the emergency department for different purposes. Pain management for such injections is of great importance to both patients and the healthcare system. Objectives Our study aimed to determine the effectiveness and safety of cryotherapy in patients receiving local anesthetic injections. Methods Subjects who presented with superficial lacerations were randomly assigned to 2 groups, the first group received ice packing prior to injection and the second did not. The pain severity, length and depth of the laceration, and the other necessary information before and after the pain-reducing intervention were measured, documented, and compared at the end of the study. Pain scores were measured using a numerical rating scale before and after the procedure, and the differences were compared using a t-test. Results Ninety subjects were enrolled in the study, 45 in each group. There were no statistical differences between the 2 groups in terms of baseline preoperative and operative characteristics (P > 0.05). The pain scores in the cryotherapy group were significantly lower before and after the procedure (P < 0.001). There was no statistically significant difference between the 2 groups for wound infection (P = 0.783). Conclusions Cooling the injection site prior to local anesthetic injection is an effective and inexpensive method to reduce the pain and discomfort caused by the injection. PMID:27847696

Synergism and antagonism in extracting local anesthetics from aqueous media with mixtures of solvents

NASA Astrophysics Data System (ADS)

Sukhanov, P. T.; Chibisova, T. V.; Korenman, Ya. I.

2014-12-01

The extraction of local anesthetics from aqueous media with mixtures of solvent is examined and its synergistic and antagonistic effects are determined. Synergism parameters, separation factors, constants for the formation of anesthetic complexes, and solvate numbers are calculated.

EFFECT OF DEUTERIUM OXIDE ON LOCAL ANESTHETIC ACTIVITY OF PROCAINE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Susina, S.V.; Hiter, F.D.; Siegel, F.P.

1962-12-01

Since it appears that D/sub 2/O is toxic in animals only when the concentration in the body fluids reaches high levels (> 20%), and since D/sub 2/O resembles the common solvent protium oxide more closely than any other, possible pharmaceutical applications of this solvent were explored. In studies in mice, D/ sub 2/O was used as a solvent for procaine and the effect on the stability and local anesthetic activity was noted. The ED/sub 50/ was determined by the method using corneal sensitivity, and comparison was made with procaine solutions in H/ sub 2/O. In H/sub 2/O the ED/sub 50/more » was 1.8% while in D/sub 2/O it was 1.0%. The LD/sub 50/was determined by intraperitoneal injection in mice. There appeared to be no significant difference in the toxicity of procaine in either solvent. Stability studies indicate that procaine is more stable in D/sub 2/O than H/sub 2/O at apparent pH values of 8.0, 8.5, and 9.0. Hence, the increased local anesthetic activity of procaine in D/sub 2/O may be accounted for by the fact that procaine free base is more stable in D/sub 2/O solutions, or that at the same apparent pH a D/sub 2/O solution of procaine will contain more free base than in the corresponding aqueous solution. (H.H.D.)« less

Transient neurologic deficit after spinal anesthesia: local anesthetic maldistribution with pencil point needles?

PubMed

Beardsley, D; Holman, S; Gantt, R; Robinson, R A; Lindsey, J; Bazaral, M; Stewart, S F; Stevens, R A

1995-08-01

Recent reports of transient neurologic deficits have raised concern about the potential toxicity of single-dose spinal 5% lidocaine in 7.5% dextrose. Two cases of volunteers who experienced minor local sensory deficits after slow (60 s) injections of 2 mL 5% lidocaine via Whitacre needles are described. One case was a result of a double injection because of a "failed" block. It seemed possible that the neurologic deficit in these cases resulted from neurotoxicity associated with maldistribution of local anesthetic. Using an in vitro spinal model, we investigated drug distribution resulting from injections through side-port spinal needles to determine whether the use of these needles could result in high local concentrations of hyperbaric solutions. A spinal canal model was fabricated using human magnetic resonance measurements. The model was placed in a surgical supine position and filled with lactated Ringer's solution to simulate the specific gravity of cerebral spinal fluid at 22 degrees C. A hyperbaric solution of phthalocyanine blue dye and dextrose (SG 1.042), simulating the anesthetic, was injected through three different needles (27-gauge 4 11/16-in. Whitacre, 25-gauge 3 1/2-in. Whitacre, 25-gauge 3 1/2-in. Quincke). Triplicate injections were done at rapid (2 mL/10 s) and slow (2 mL/60 s) rates, with needle side ports oriented in a sacral and cephalad direction. At slow rates of injection, using 27- or 25-gauge sacrally directed Whitacre needles, injections showed evidence of maldistribution with extrapolated peak sacral lidocaine concentrations reaching 2.0%. In contrast, distribution after slow injection through sacrally directed Quincke needles was uniform.(ABSTRACT TRUNCATED AT 250 WORDS)

Densities of dextrose-free intrathecal local anesthetics, opioids, and combinations measured at 37 degrees C.

PubMed

Richardson, M G; Wissler, R N

1997-01-01

Dextrose-free anesthetic medications are commonly used to provide subarachnoid anesthesia and analgesia. Hypobaricity has been proposed as a mechanism to explain postural effects on the extent of sensory block produced by these drugs. Densities of dextrose-free solutions of local anesthetics and opioids, and commonly used anesthetic/opioid mixtures were determined at 37.00 degrees C for comparison with the density of human cerebrospinal fluid (CSF). Measurements accurate to 0.00001 g/mL were performed using a mechanical oscillation resonance frequency density meter. All undiluted solutions tested are hypobaric relative to human lumbar CSF with the exception of lidocaine 1.5% and 2.0% with epinephrine 1:200,000. All mixtures of local anesthetics and opioids tested are hypobaric. We observed good agreement between measured densities and calculated weighted average densities of anesthetic mixtures. While the influence of baricity on the clinical effects of dextrose-free intrathecal anesthetics remains controversial, attempts to attribute postural effects to the baricity of these drugs requires establishment of accurate density values. These density data may facilitate elucidation of the mechanisms underlying the behavior of dextrose-free intrathecal anesthetics.

Vasoconstrictors in local anesthesia for dentistry.

PubMed Central

Sisk, A. L.

1992-01-01

Addition of a vasoconstrictor to a local anesthetic may have several beneficial effects: a decrease in the peak plasma concentration of the local anesthetic agent, increase in the duration and the quality of anesthesia, reduction of the minimum concentration of anesthetic needed for nerve block, and decrease of blood loss during surgical procedures. The addition of a vasoconstrictor to a local anesthetic may also have detrimental effects. A review of the literature indicates that vasoconstrictor concentrations in local anesthetics marketed for dental use in the United States are not always optimal to achieve the purposes for which they are added. In most cases, a reduced concentration of vasoconstrictor could achieve the same goal as the marketed higher concentration, with less side-effect liability. PMID:8250339

Pain management in total knee arthroplasty by intraoperative local anesthetic application and one-shot femoral block

PubMed Central

Sigirci, Aykut

2017-01-01

Background: Pain after total knee arthroplasty (TKA) is a big problem in orthopaedic surgery. Although opioids and continuous epidural analgesia remain the major options for the postoperative pain management of TKA, they have some undesirable side effects. Epidural analgesia is technically demanding, and the patient requires close monitoring. Different types of local anesthetic applications can successfully treat TKA pain. Local anesthetics have the advantage of minimizing pain at the source. This study investigates the efficacy of different local anesthetic application methods on early, (1st day) pain control after total knee arthroplasty. Materials and Methods: 200 patients who underwent unilateral TKA surgery under spinal anesthesia were randomly assigned into four different groups (fifty in each group) and were administered pain control by different peri- and postoperative regimens. Group A was the control group wherein no postsurgical analgesia was administered to assess spinal anesthesia efficacy; in Group B, only postsurgical one-shot femoral block was applied; in Group C, intraoperative periarticular local anesthetic was applied; in Group D, a combination of the one-shot femoral block and intraoperative periarticular local anesthetics were applied. Demographic data consisting of age, weight, gender and type of deformity of patients were collected. The data did not differ significantly between the four groups. Results: Group D patients experienced significantly better postoperative pain relief (P < 0.05) and were therefore more relaxed in pain (painless time, VAS score) and knee flexion (degrees) than the other patient groups in the 1st postoperative day followup. Painless time of Group D was 10.5 hours and was better than Group C (6.8 hours), Group B (6.2 hours) and Group A (3.0 hours) (P < 0.05). Group A got the best pain Vas score degrees in the 1st postoperative day which showed the success of combined periarticülar local anesthetic injection and

Pain management in total knee arthroplasty by intraoperative local anesthetic application and one-shot femoral block.

PubMed

Sigirci, Aykut

2017-01-01

Pain after total knee arthroplasty (TKA) is a big problem in orthopaedic surgery. Although opioids and continuous epidural analgesia remain the major options for the postoperative pain management of TKA, they have some undesirable side effects. Epidural analgesia is technically demanding, and the patient requires close monitoring. Different types of local anesthetic applications can successfully treat TKA pain. Local anesthetics have the advantage of minimizing pain at the source. This study investigates the efficacy of different local anesthetic application methods on early, (1 st day) pain control after total knee arthroplasty. 200 patients who underwent unilateral TKA surgery under spinal anesthesia were randomly assigned into four different groups (fifty in each group) and were administered pain control by different peri- and postoperative regimens. Group A was the control group wherein no postsurgical analgesia was administered to assess spinal anesthesia efficacy; in Group B, only postsurgical one-shot femoral block was applied; in Group C, intraoperative periarticular local anesthetic was applied; in Group D, a combination of the one-shot femoral block and intraoperative periarticular local anesthetics were applied. Demographic data consisting of age, weight, gender and type of deformity of patients were collected. The data did not differ significantly between the four groups. Group D patients experienced significantly better postoperative pain relief ( P < 0.05) and were therefore more relaxed in pain (painless time, VAS score) and knee flexion (degrees) than the other patient groups in the 1 st postoperative day followup. Painless time of Group D was 10.5 hours and was better than Group C (6.8 hours), Group B (6.2 hours) and Group A (3.0 hours) ( P < 0.05). Group A got the best pain Vas score degrees in the 1 st postoperative day which showed the success of combined periarticülar local anesthetic injection and femoral nerve block. The intraoperative

The efficacy of an intraosseous injection system of delivering local anesthetic.

PubMed

Leonard, M S

1995-01-01

This article describes the clinical testing of a new system for the intraosseous delivery of local anesthesia. The author concluded that the system delivered local anesthetic very effectively (in some situations more effectively than the traditional delivery method), thus offering a great potential advantage to both dentists and patients.

Clinical Concentrations of Local Anesthetics Bupivacaine and Lidocaine Differentially Inhibit Human Kir2.x Inward Rectifier K+ Channels.

PubMed

Nakahira, Kei; Oshita, Kensuke; Itoh, Masayuki; Takano, Makoto; Sakaguchi, Yoshiro; Ishihara, Keiko

2016-04-01

Inward rectifier K channels of the Kir2.x subfamily are widely expressed in neuronal tissues, controlling neuronal excitability. Previous studies reported that local anesthetics (LAs) do not affect Kir2 channels. However, the effects have not been studied at large concentrations used in regional anesthesia. This study used the patch-clamp technique to examine the effects of bupivacaine and lidocaine on Kir2.1, Kir2.2, and Kir2.3 channels expressed in human embryonic kidney 293 cells. When applied extracellularly in whole-cell recordings, both LAs inhibited Kir2.x currents in a voltage-independent manner. Inhibition with bupivacaine was slow and irreversible, whereas that with lidocaine was fast and reversible. Kir2.3 displayed a greater sensitivity to bupivacaine than Kir2.1 and Kir2.2 (50% inhibitory concentrations at approximately 5 minutes, 0.6 vs 8-10 mM), whereas their sensitivities to lidocaine were similar (50% inhibitory concentrations, 1.5-2.7 mM). Increases in the charged/neutral ratio of the LAs at an acidic extracellular pH attenuated their inhibitory effects, and a permanently charged lidocaine derivative QX-314 exhibited no effects when applied extracellularly. Inside-out experiments demonstrated that inhibition of Kir2.1 with cytoplasmic lidocaine and QX-314 was rapid and reversible, whereas that induced by bupivacaine was slow and irreversible. Furthermore, dose-inhibition relations for the charged form of bupivacaine and lidocaine obtained at different cytoplasmic pHs could be approximated by a single relation for each LA. The results indicate that both LAs at clinical concentrations equilibrated rapidly with the intracellular milieu, differentially inhibiting Kir2.x channel function from the cytoplasmic side.

Anesthetic action of volatile anesthetics by using Paramecium as a model.

PubMed

Zhou, Miaomiao; Xia, Huimin; Xu, Younian; Xin, Naixing; Liu, Jiao; Zhang, Shihai

2012-06-01

Although empirically well understood in their clinical administration, volatile anesthetics are not yet well comprehended in their mechanism studies. A major conundrum emerging from these studies is that there is no validated model to assess the presumed candidate sites of the anesthetics. We undertook this study to test the hypothesis that the single-celled Paramecium could be anesthetized and served as a model organism in the study of anesthetics. We assessed the motion of Paramecium cells with Expert Vision system and the chemoresponse of Paramecium cells with T-maze assays in the presence of four different volatile anesthetics, including isoflurane, sevoflurane, enflurane and ether. Each of those volatiles was dissolved in buffers to give drug concentrations equal to 0.8, 1.0, and 1.2 EC50, respectively, in clinical practice. We could see that after application of volatile anesthetics, the swimming of the Paramecium cells was accelerated and then suppressed, or even stopped eventually, and the index of the chemoresponse of the Paramecium cells (denoted as I ( che )) was decreased. All of the above impacts were found in a concentration-dependent fashion. The biphasic effects of the clinical concentrations of volatile anesthetics on Paramecium simulated the situation of high species in anesthesia, and the inhibition of the chemoresponse also indicated anesthetized. In conclusion, the findings in our studies suggested that the single-celled Paramecium could be anesthetized with clinical concentrations of volatile anesthetics and therefore be utilized as a model organism to study the mechanisms of volatile anesthetics.

Anesthetic Agents of Plant Origin: A Review of Phytochemicals with Anesthetic Activity.

PubMed

Tsuchiya, Hironori

2017-08-18

The majority of currently used anesthetic agents are derived from or associated with natural products, especially plants, as evidenced by cocaine that was isolated from coca ( Erythroxylum coca , Erythroxylaceae) and became a prototype of modern local anesthetics and by thymol and eugenol contained in thyme ( Thymus vulgaris , Lamiaceae) and clove ( Syzygium aromaticum , Myrtaceae), respectively, both of which are structurally and mechanistically similar to intravenous phenolic anesthetics. This paper reviews different classes of phytochemicals with the anesthetic activity and their characteristic molecular structures that could be lead compounds for anesthetics and anesthesia-related drugs. Phytochemicals in research papers published between 1996 and 2016 were retrieved from the point of view of well-known modes of anesthetic action, that is, the mechanistic interactions with Na⁺ channels, γ-aminobutyric acid type A receptors, N -methyl-d-aspartate receptors and lipid membranes. The searched phytochemicals include terpenoids, alkaloids and flavonoids because they have been frequently reported to possess local anesthetic, general anesthetic, antinociceptive, analgesic or sedative property. Clinical applicability of phytochemicals to local and general anesthesia is discussed by referring to animal in vivo experiments and human pre-clinical trials. This review will give structural suggestions for novel anesthetic agents of plant origin.

A novel local anesthetic system: transcriptional transactivator peptide-decorated nanocarriers for skin delivery of ropivacaine.

PubMed

Chen, Chuanyu; You, Peijun

2017-01-01

Barrier properties of the skin and physicochemical properties of drugs are the main factors for the delivery of local anesthetic molecules. The present work evaluates the anesthetic efficacy of drug-loaded nanocarrier (NC) systems for the delivery of local anesthetic drug, ropivacaine (RVC). In this study, transcriptional transactivator peptide (TAT)-decorated RVC-loaded NCs (TAT-RVC/NCs) were successfully fabricated. Physicochemical properties of NCs were determined in terms of particle size, zeta potential, drug encapsulation efficiency, drug-loading capacity, stability, and in vitro drug release. The skin permeation of NCs was examined using a Franz diffusion cell mounted with depilated mouse skin in vitro, and in vivo anesthetic effect was evaluated in mice. The results showed that TAT-RVC/NCs have a mean diameter of 133.2 nm and high drug-loading capacity of 81.7%. From the in vitro skin permeation results, it was observed that transdermal flux of TAT-RVC/NCs was higher than that of RVC-loaded NCs (RVC/NCs) and RVC injection. The evaluation of in vivo anesthetic effect illustrated that TAT-RVC/NCs can enhance the transdermal delivery of RVC by reducing the pain threshold in mice. These results indicate that TAT-decorated NCs systems are useful for overcoming the barrier function of the skin, decreasing the dosage of RVC and enhancing the anesthetic effect. Therefore, TAT-decorated NCs can be used as an effective transdermal delivery system for local anesthesia.

New Updates Pertaining to Drug Delivery of Local Anesthetics in Particular Bupivacaine Using Lipid Nanoparticles

NASA Astrophysics Data System (ADS)

Beiranvand, Siavash; Eatemadi, Ali; Karimi, Arash

2016-06-01

Lipid nanoparticles (liposomes) were first described in 1965, and several work have led to development of important technical advances like triggered release liposomes and drug-loaded liposomes. These advances have led to numerous clinical trials in such diverse areas such as the delivery of anti-cancer, antifungal, and antibiotic drugs; the delivery of gene medicines; and most importantly the delivery of anesthesia drugs. Quite a number of liposomes are on the market, and many more are still in developmental stage. Lipid nanoparticles are the first nano-medicine delivery system to be advanced from laboratory concept to clinical application with high considerable clinical acceptance. Drug delivery systems for local anesthetics (LAs) have caught the interest of many researchers because there are many biomedical advantages connected to their application. There have been several formulation techniques to systemically deliver LA that include encapsulation in liposomes and complexation in cyclodextrins, nanoparticles, and to a little extent gold nanoparticles. The proposed formulations help to decrease the LA concentration utilized, increase its permeability, and most importantly increase the localization of the LA for a long period of time thereby leading to increase in the duration of the LA effect and finally to reduce any local and systemic toxicity. In this review, we will highlight on new updates pertaining to drug delivery of local anesthetics in particular bupivacaine using lipid nanoparticles.

New Updates Pertaining to Drug Delivery of Local Anesthetics in Particular Bupivacaine Using Lipid Nanoparticles.

PubMed

Beiranvand, Siavash; Eatemadi, Ali; Karimi, Arash

2016-12-01

Lipid nanoparticles (liposomes) were first described in 1965, and several work have led to development of important technical advances like triggered release liposomes and drug-loaded liposomes. These advances have led to numerous clinical trials in such diverse areas such as the delivery of anti-cancer, antifungal, and antibiotic drugs; the delivery of gene medicines; and most importantly the delivery of anesthesia drugs. Quite a number of liposomes are on the market, and many more are still in developmental stage. Lipid nanoparticles are the first nano-medicine delivery system to be advanced from laboratory concept to clinical application with high considerable clinical acceptance. Drug delivery systems for local anesthetics (LAs) have caught the interest of many researchers because there are many biomedical advantages connected to their application. There have been several formulation techniques to systemically deliver LA that include encapsulation in liposomes and complexation in cyclodextrins, nanoparticles, and to a little extent gold nanoparticles. The proposed formulations help to decrease the LA concentration utilized, increase its permeability, and most importantly increase the localization of the LA for a long period of time thereby leading to increase in the duration of the LA effect and finally to reduce any local and systemic toxicity. In this review, we will highlight on new updates pertaining to drug delivery of local anesthetics in particular bupivacaine using lipid nanoparticles.

A Comparative Study between the Effect of Combined Local Anesthetic and Low-dose Ketamine with Local Anesthetic on Postoperative Complications after Impacted Third Molar Surgery.

PubMed

Kumar, Anuj; Kale, Tejraj Pundalik

2015-12-01

Postoperative pain, swelling and trismus are the most common outcome after third molar surgery. Many methods have been tried to improve postoperative comfort after surgery. Ketamine is a phencyclidine derivative that induces a state of dissociative anesthesia. It is a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist and has a distinct suppression effect on central nervous system (CNS) sensitization. Ketamine in a subanesthetic dose is set to produce analgesic and anti-inflammatory effect. Sixty patients, between the age group of 18 and 38 years, undergoing the extraction of impacted mandibular third molar, reporting to the department of oral and maxillofacial surgery were included in the study. Patients were divided randomly into two groups: local anesthetic alone (LAA) and local anesthetic and ketamine (LAK). Statistical analysis was performed using the Mann-Whitney U/unpaired--t-test and Wilcoxon signed-rank test. There was a significant difference in mouth opening in the LAA and LAK group in the immediate postoperative period. There was a significant difference between the two groups after 1 hour (LAA: 2.37; LAK: 1.40), and 4 hours (LAA: 2.37; LAK: 1.40). There was a significant difference in terms of facial swelling in the immediate postoperative period and day 1 between the LAA and LAK group. Use of subanesthetic dose of ketamine is not only safe but also valuable in reducing patient morbidity after third molar surgery. Combination of a local anesthetic and subanesthetic dose of ketamine during surgical extraction of third molars provides good postoperative analgesia with less swelling and significantly less trismus.

Comparison between newer local anesthetics for myofascial pain syndrome management.

PubMed

Zaralidou, A Th; Amaniti, E N; Maidatsi, P G; Gorgias, N K; Vasilakos, D F

2007-06-01

Myofascial pain syndromes are characterized by the presence of painful loci within muscles, tendons or ligaments, called trigger points. Infiltration of these points with local anesthetics is often used as a treatment modality. The aim of the study was to comparatively evaluate 0.25% levobupivacaine and 0.25% ropivacaine for trigger point injection regarding pain on injection, treatment efficacy and duration of symptoms remission. Sixty-eight patients, suffering from myofascial pain syndromes, were randomly assigned to two groups to receive either levobupivacaine or ropivacaine for trigger-point injection. After completion of the procedure, patients were asked to rate pain during injection and efficacy of the treatment, based on immediate relief. Two weeks later, they were asked about the duration of this relief. Statistical analysis did not reveal significant differences between groups with respect to pain during injection, efficacy of the treatment and duration of pain relief. The two local anesthetics seem to be equally effective for trigger point infiltration. (c) 2007 Prous Science. All rights reserved.

A Combination of Dexmedetomidine and Lidocaine Is a Cardiovascularly Safe Dental Local Anesthetic for Hypertensive Rats Treated With a Nonselective β-Adrenergic Antagonist.

PubMed

Tsutsui, Yukako; Sunada, Katsuhisa

2017-01-01

Hypertensive patients receiving nonselective β-adrenergic antagonists are vulnerable to hypertension and bradycardia when injected with dental local anesthetic formulations containing epinephrine. Dexmedetomidine (DEX), an α 2 -adrenergic agonist, has been reported to prolong and enhance the local anesthetic effects of lidocaine. The cardiovascular effects of the DEX-lidocaine combination have not yet been investigated in the presence of nonselective β-adrenergic antagonists. Therefore, we assessed the cardiovascular effects of the DEX-lidocaine combination in spontaneously hypertensive rats (SHR) treated with a nonselective β-adrenergic antagonist (propranolol). We injected propranolol-treated rats with various concentrations of DEX alone, 100 μg/kg epinephrine alone, or 5 μg/kg DEX combined with 2% lidocaine and measured their blood pressure (BP) and heart rates (HR) to assess the cardiovascular effects. The BP of propranolol-treated SHR was significantly increased by treatment with 100 μg/kg epinephrine alone. The BP and HR of propranolol-treated SHR were not significantly changed by treatment with low concentrations of DEX, but they were significantly decreased by treatment with a high concentration of DEX (50 μg/kg). Moreover, there was no significant difference in the BP and HR of propranolol-treated SHR after the injection of a combination of 5 μg/kg DEX and 2% lidocaine. Thus, the DEX-lidocaine combination may be an acceptable addition to dental local anesthetic solutions from a cardiovascular standpoint for hypertensive patients receiving nonselective β-adrenergic antagonists.

Particulate contamination of local anesthetic solutions.

PubMed

Cooley, R L; Lubow, R M

1981-05-01

Particulate contamination was found in one particular lot number of local anesthetic, lidocaine with 1:100,000 epinephrine. The contaminants were noticed in several cartridges of each container and varied in size from minute to several millimeters. Analysis of the foreign matter revealed the particles to be of a way or puttylike consistency; however, the sterility of the solution was not altered and the pH was still within acceptable limits. The contaminant was most likely wax or a combination of wax, silicone, and glycerin, which are constituents of the rubber stopper and its associated lubricants. This problem was most likely due to temperature changes during storage and shipment, but it was also possibly due to manufacturing discrepancies.

An alternative choice of lidocaine-loaded liposomes: lidocaine-loaded lipid-polymer hybrid nanoparticles for local anesthetic therapy.

PubMed

Wang, Jianguo; Zhang, Laizhu; Chi, Huimin; Wang, Shilei

2016-05-01

The skin permeation enhancement of local anesthetics by newer innovative nanotechnologies has been an appealing field recently. However, which nanocarrier is better for drug loading and has better stability? Therefore, the aim of our study was to compare two kinds of nanocarriers: liposomes and lipid-polymer hybrid nanoparticles (LPNs) for lidocaine (LA) delivery. LA-loaded liposomes (LA-LPs) and LPNs (LA-LPNs) were prepared. Two kinds of nanocarriers were characterized in terms of particle size, zeta potential, drug encapsulation efficiency (EE), drug release, and stability. Their in vitro skin permeation was studied using a Franz diffusion cell mounted with depilated mouse skin in vitro. In vivo local anesthetic effects of LA containing formulations were evaluated by tail flick latency (TFL) test using a tail-flick measuring device. Compared with LA-LPs, LA-LPNs showed significantly better in vitro skin permeation ability and in vivo local anesthetic effects. The results demonstrated that LPNs could improve the efficacy of drugs to higher levels than LPs and free drugs, thus could serve as an effective drug system for LA loading for local anesthetic therapy.

Which one is more effective for analgesia in infratentorial craniotomy? The scalp block or local anesthetic infiltration.

PubMed

Akcil, Eren Fatma; Dilmen, Ozlem Korkmaz; Vehid, Hayriye; Ibısoglu, Lutfiye Serap; Tunali, Yusuf

2017-03-01

The most painful stages of craniotomy are the placement of the pin head holder and the skin incision. The primary aim of the present study is to compare the effects of the scalp block and the local anesthetic infiltration with bupivacaine 0.5% on the hemodynamic response during the pin head holder application and the skin incision in infratentorial craniotomies. The secondary aims are the effects on pain scores and morphine consumption during the postoperative 24h. This prospective, randomized and placebo controlled study included forty seven patients (ASA I, II and III). The scalp block was performed in the Group S, the local anesthetic infiltration was performed in the Group I and the control group (Group C) only received remifentanil as an analgesic during the intraoperative period. The hemodynamic response to the pin head holder application and the skin incision, as well as postoperative pain intensity, cumulative morphine consumption and opioid related side effects were compared. The scalp block reduced the hemodynamic response to the pin head holder application and the skin incision in infratentorial craniotomies. The local anesthetic infiltration reduced the hemodynamic response to the skin incision. As well as both scalp block and local anesthetic infiltration reduced the cumulative morphine consumption in postoperative 24h. Moreover, the pain intensity was lower after scalp block in the early postoperative period. The scalp block may provide better analgesia in infratentorial craniotomies than local anesthetic infiltration. Copyright © 2017 Elsevier B.V. All rights reserved.

Postoperative pain and preemptive local anesthetic infiltration in hallux valgus surgery.

PubMed

Gądek, Artur; Liszka, Henryk; Wordliczek, Jerzy

2015-03-01

Several techniques of anesthesia are used in foot surgery. Preemptive analgesia helps to prevent the development of hypersensitivity in the perioperative period. The aim of our study was to assess the role of preemptive local anesthetic infiltration and postoperative pain after hallux valgus surgery. We evaluated 118 patients who underwent modified chevron and mini-invasive Mitchell-Kramer bunionectomy of the first distal metatarsal. After spinal anesthesia each patient randomly received an infiltration of local anesthetic or the same amount of normal saline 10 minutes before the skin incision. We measured the intensity of pain 4, 8, 12, 16, 24, and 72 hours after the release of the tourniquet using a visual analogue scale (VAS). Rescue analgesia and all other side effects were noted. Preemptive analgesia resulted in less pain during the first 24 hours after surgery. The decrease of VAS score was significantly lower in the study group during all the short postoperative periods measured. The rescue analgesia was administered in 11.9% of patients in the injected group and 42.4% in the placebo group (P < .05). In the injected group we did not observe significant difference in VAS score between patients post-chevron and miniinvasive Mitchell-Kramer osteotomy of the first distal metatarsal. No systemic adverse effects were noted. One persistent injury of dorsomedial cutaneous nerve was observed. Preemptive local anesthetic infiltration was an efficient and safe method to reduce postoperative pain after hallux valgus surgery. The analgesic effect was satisfactory in both traditional and minimally invasive techniques. © The Author(s) 2014.

Isoflurane waste anesthetic gas concentrations associated with the open-drop method.

PubMed

Taylor, Douglas K; Mook, Deborah M

2009-01-01

The open-drop technique is used frequently for anesthetic delivery to small rodents. Operator exposure to waste anesthetic gas (WAG) is a potential occupational hazard if this method is used without WAG scavenging. This study was conducted to determine whether administration of isoflurane by the open-drop technique without exposure controls generates significant WAG concentrations. We placed 0.1, 0.2, or 0.3 ml of liquid isoflurane into screw-top 500 or 1000 ml glass jars. WAG concentration was measured at the opening of the container and 20 and 40 cm from the opening, a distance at which users likely would operate, at 1, 2, or 3 min WAG was measured by using a portable infrared gas analyzer. Mean WAG concentrations at the vessel opening were as high as 662 +/- 168 ppm with a 500 ml jar and 122 +/- 87 ppm with a 1000 ml jar. At operator levels, WAG concentrations were always at or near 0 ppm. For measurements made at the vessel opening, time was the only factor that significantly affected WAG concentration when using the 500 ml jar. Neither time nor liquid volume were significant factors when using 1000 ml jar. At all liquid volumes and time points, the WAG concentration associated with using the 500 ml container was marginally to significantly greater than that for the 1000 ml jar.

Comparison between analgesic effect of bupivacaine thoracic epidural and ketamine infusion plus wound infiltration with local anesthetics in open cholecystectomy.

PubMed

Megahed, Nagwa Ahmed Ebrahim; Ellakany, Mohamed; Elatter, Ahmed Mohammed Ibrahim; Moustafa Teima, Mohamed Ahmed Ali

2014-01-01

Neuraxial blocks result in sympathetic block, sensory analgesia and motor block. Continuous epidural anesthesia through a catheter offers several options for perioperative analgesia. Local anesthetic boluses or infusions can provide profound analgesia. Although the role of low-dose ketamine (<2 mg/kg intramuscular, <1 mg/kg intravenous [IV] or ≤ 20 μg/kg/min by IV infusion) in the treatment of post-operative pain is controversial, perioperative administration of a small dose of ketamine may be valuable to a multimodal analgesic regimen. A local anesthetic can be used for wound infiltration intra-operative to minimized the surgical pain. A prospective randomized study was performed in which 40 patients scheduled for elective open cholecystectomy under general anesthesia admitted to the Medical Research Institute were included and further subdivided into two groups, group A, received thoracic epidural catheter at T7-8, activation was done 20 min before induction of anesthesia with plain bupivacaine at a concentration of 0.25% at a volume of 1 ml/segment aiming to block sensory supply from T4-L2, then received continuous thoracic epidural infusion intra and postoperatively with plain bupivacaine at a concentration of 0.125% at a rate of 5 ml/h for 24 h, group B received 0.3 mg/kg bolus of ketamine at the time of induction then 0.1 mg/kg/h ketamine IV infusion during surgery followed by wound infiltration with 15 ml of plain bupivacaine 0.5% at the time of skin closure. Bupivacaine thoracic epidural analgesia had better control on heart rate and mean arterial blood pressure than ketamine infusion plus wound infiltration with local anesthetic in patients undergoing open cholecystectomy. Thoracic epidural analgesia had better control on hemodynamic changes intra-and postoperatively than ketamine infusion with local wound infiltration in open cholecystectomy.

Local Anesthetic Systemic Toxicity: A Review of Recent Case Reports and Registries.

PubMed

Gitman, Marina; Barrington, Michael J

2018-02-01

This review summarizes presenting features, management, and outcomes of local anesthetic systemic toxicity (LAST) from published cases and those submitted to online registries capturing use of intravenous lipid emulsion (ILE) therapy. The results of single-center and multicenter registries and epidemiologic studies complement this information. Between March 2014 and November 2016, 47 separate cases of LAST were described in 35 peer-reviewed articles. Local anesthetic systemic toxicity events occurred as a result of penile blocks (23%), local infiltration (17%), and upper/lower extremity, torso, and neuraxial blockade. Twenty-two patients (47%) were treated with ILE, and 2 patients (4.3%) died. During the same time period, 11 cases submitted to lipidrescue.org were treated with ILE and survived. The incidence of LAST reported in registries is 0.03% or 0.27 (95% confidence interval, 0.21-0.35) per 1000 peripheral nerve blocks (denominator of 251,325). Seizure (53% and 61% from case reports and registries, respectively) was the most common presenting feature.

A novel approach to scavenging anesthetic gases in rodent surgery.

PubMed

Nesbitt, Jeffrey C; Krageschmidt, Dale A; Blanco, Michael C

2013-01-01

Laboratory animal procedures using gas anesthetics may amass elevated waste gas concentrations in operating rooms if controls are not implemented for capturing and removing the vapors. Area sampling using an infrared analyzer indicated isoflurane concentrations likely to exceed occupational exposure guidelines. Our study showed environmental concentrations of oxygen as high as 40% and isoflurane concentrations >100 ppm when no controls or merely passive controls were utilized. These extraneous isoflurane emissions were determined to be originating from the pre-procedural induction process as well as the gas delivery nose cone. A novel waste gas collection cylinder was designed to enclose the gas delivery nose cone and animal head during the administration of anesthetic gases. The vented cylinder utilized a house vacuum to remove the waste anesthetic gases from the surgical field. A commercially available induction chamber designed to be actively and externally exhausted was used to lower concentrations during the induction process. With implementation of local exhaust ventilation controls, waste anesthetic gas concentrations decreased to below recommended occupational exposure levels. In vitro (sham) testing compared favorably to in vivo measurements validating the reduction capability of active ventilation during rodent anesthetic administration. In vivo isoflurane reductions for the induction chamber emissions, the operating room, and the surgeon's breathing zone were 95%, 60%, and 53%, respectively. The same measurements for an in vitro procedure were 98%, 84%, and 87%, respectively.

Peripheral nerve catheters and local anesthetic infiltration in perioperative analgesia.

PubMed

Merritt, Christopher K; Mariano, Edward R; Kaye, Alan David; Lissauer, Jonathan; Mancuso, Kenneth; Prabhakar, Amit; Urman, Richard D

2014-03-01

Peripheral nerve catheters (PNCs) and local infiltration analgesia (LIA) represent valuable options for controlling perioperative pain. PNCs have been increasingly utilized to provide both surgical anesthesia and prolonged postoperative analgesia for a wide variety of procedures. PNCs can be more technically challenging to place than typical single-injection nerve blocks (SINB), and familiarity with the indications, contraindications, relevant anatomy, and appropriate technical skills is a prerequisite for the placement of any PNC. PNCs include risks of peripheral nerve injury, damage to adjacent anatomic structures, local anesthetic toxicity, intravascular injection, risks associated with motor block, risks of unnoticed injury to the insensate limb, and risks of sedation associated with PNC placement. In addition to these common risks, there are specific risks unique to each PNC insertion site. LIA strategies have emerged that seek to provide the benefit of targeted local anesthesia while minimizing collateral motor block and increasing the applicability of durable local anesthesia beyond the extremities. LIA involves the injection and/or infusion of a local anesthetic near the site of surgical incision to provide targeted analgesia. A wide variety of techniques have been described, including single-injection intraoperative wound infiltration, indwelling wound infusion catheters, and the recent high-volume LIA technique associated with joint replacement surgery. The efficacy of these techniques varies depending on specific procedures and anatomic locations. The recent incorporation of ultra-long-acting liposomal bupivacaine preparations has the potential to dramatically increase the utility of single-injection LIA. LIA represents a promising yet under-investigated method of postoperative pain control. Copyright © 2014 Elsevier Ltd. All rights reserved.

Selective local anesthetic placement using ultrasound guidance and neurostimulation for infraclavicular brachial plexus block.

PubMed

Bowens, Clifford; Gupta, Rajnish K; O'Byrne, William T; Schildcrout, Jonathan S; Shi, Yaping; Hawkins, Jermel J; Michaels, Damon R; Berry, James M

2010-05-01

In this study, we performed the infraclavicular block with combined ultrasound guidance and neurostimulation to selectively target cords to compare the success rates of placing a single injection of local anesthetic either in a central or peripheral location. Two hundred eighteen patients were enrolled in a consecutive, prospective study. Patients were randomized to injection of local anesthetic either centrally (posterior cord) or peripherally (medial or lateral cord) using ultrasound guidance and neurostimulation. Supervised senior anesthesiology residents or attending anesthesiologists performed the blocks. Both intent-to-treat and treatment-received analyses were used to compare central and peripheral placement efficacy. The overall success rate was significantly higher for the central placements than peripheral placements (96% vs 85%, P = 0.004). Individual cord success rates were as follows: posterior 99%, lateral 92%, and medial 84% (P = 0.001). The central group required attending physician intervention more frequently (27% vs 6%, P < 0.001). Postoperative pain scores of < or =3 were more likely with central placement (100% vs 94%, P = 0.012). Central placement of a single injection of local anesthetic targeted at the posterior cord resulted in a higher success rate for infraclavicular block.

Pregnancy outcome after in utero exposure to local anesthetics as part of dental treatment: A prospective comparative cohort study.

PubMed

Hagai, Aharon; Diav-Citrin, Orna; Shechtman, Svetlana; Ornoy, Asher

2015-08-01

Dental treatment and use of local anesthetics during pregnancy generally are considered harmless because of lack of evidence of adverse pregnancy effects. Data on the safety of dental treatment and local anesthetics during pregnancy are scant. Dental care is often a reason for concern both among women and their health care providers. The primary objective of this study was to evaluate the rate of major anomalies after exposure to local anesthetics as part of dental care during pregnancy. The authors performed a prospective, comparative observational study at the Israeli Teratology Information Services between 1999 and 2005. The authors followed 210 pregnancies exposed to dental local anesthetics (112 [53%] in the first trimester) and compared them with 794 pregnancies not exposed to teratogens. The rate of major anomalies was not significantly different between the groups (4.8% versus 3.3%, P = .300). There was no difference in the rate of miscarriages, gestational age at delivery, or birth weight. The most common types of dental treatment were endodontic treatment (43%), tooth extraction (31%), and tooth restoration (21%). Most women (63%) were not exposed to additional medications. Approximately one-half (51%) of the women were not exposed to dental radiography, and 44% were exposed to radiation, mostly bite-wing radiography. This study's results suggest that use of dental local anesthetics, as well as dental treatment during pregnancy, do not represent a major teratogenic risk. There seems to be no reason to prevent pregnant women from receiving dental treatment and local anesthetics during pregnancy. Copyright © 2015 American Dental Association. Published by Elsevier Inc. All rights reserved.

[Comparative effects of vitamin C on the effects of local anesthetics ropivacaine, bupivacaine, and lidocaine on human chondrocytes].

PubMed

Tian, Jun; Li, Yan

2016-01-01

Intra-articular injections of local anesthetics are commonly used to enhance post-operative analgesia following orthopedic surgery as arthroscopic surgeries. Nevertheless, recent reports of severe complications due to the use of intra-articular local anesthetic have raised concerns. The study aims to assess use of vitamin C in reducing adverse effects of the most commonly employed anesthetics - ropivacaine, bupivacaine and lidocaine - on human chondrocytes. The chondrocyte viability following exposure to 0.5% bupivacaine or 0.75% ropivacaine or 1.0% lidocaine and/or vitamin C at doses 125, 250 and 500μM was determined by Live/Dead assay and annexin V staining. Expression levels of caspases 3 and 9 were assessed using antibodies by Western blotting. Flow cytometry was performed to analyze the generation of reactive oxygen species. On exposure to the local anesthetics, chondrotoxicity was found in the order ropivacainelocal anesthetics ropivacaine, bupivacaine and lidocaine. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Comparative effects of vitamin C on the effects of local anesthetics ropivacaine, bupivacaine, and lidocaine on human chondrocytes.

PubMed

Tian, Jun; Li, Yan

2016-01-01

Intra-articular injections of local anesthetics are commonly used to enhance post-operative analgesia following orthopedic surgery as arthroscopic surgeries. Nevertheless, recent reports of severe complications due to the use of intra-articular local anesthetic have raised concerns. The study aims to assess use of vitamin C in reducing adverse effects of the most commonly employed anesthetics - ropivacaine, bupivacaine and lidocaine - on human chondrocytes. The chondrocyte viability following exposure to 0.5% bupivacaine or 0.75% ropivacaine or 1.0% lidocaine and/or vitamin C at doses 125, 250 and 500 μM was determined by LIVE/DEAD assay and annexin V staining. Expression levels of caspases 3 and 9 were assessed using antibodies by Western blotting. Flow cytometry was performed to analyze the generation of reactive oxygen species. On exposure to the local anesthetics, chondrotoxicity was found in the order ropivacainelocal anesthetics ropivacaine, bupivacaine and lidocaine. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

[The influence of local anesthetics on human leukocyte functions studied by micro whole blood collection and flowcytometry].

PubMed

Okuno, S; Noda, H; Kugimiya, T; Saionji, K

1996-03-01

The influence of local anesthetics (pure bupivacaine and lidocaine with no preservative) on human leukocyte functions was examined. (a) The effect of bupivacaine on the phagocytosis of granulocyte was studied by bioassay. (b) The effect of lidocaine on the appearance of iC3b receptor (CR3) of granulocyte and monocyte (which is an important cell-adhesion-factor) was examined using flowcytometry. (c) The influence of lidocaine on phagocytosis of granulocyte and monocyte and on respiratory burst of granulocyte was examined using flowcytometry. (d) The influence of lidocaine on phagocytosis and that on respiratory burst were compared. These studies revealed that both phagocytosis and respiratory burst were inhibited by lidocaine, and the inhibition of respiratory burst was stronger than the inhibition of phagocytosis by local anesthetics' immunosuppressive effects. It was concluded that the balance of immunosuppressive action due to antimicrobial action and bactericidal ability of local anesthetics determined the occurrence of local bacterial infection.

Effects of Epidural Labor Analgesia With Low Concentrations of Local Anesthetics on Obstetric Outcomes: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

PubMed

Wang, Ting-Ting; Sun, Shen; Huang, Shao-Qiang

2017-05-01

Low concentrations of local anesthetics (LCLAs) are increasingly popular for epidural labor analgesia. The effects of epidural analgesia with low concentrations of anesthetics on the duration of the second stage of labor and the instrumental birth rate, however, remain controversial. A systematic review was conducted to compare the effects of epidural analgesia with LCLAs with those of nonepidural analgesia on obstetric outcomes. The databases of PubMed, Embase, and the Cochrane controlled trials register were independently searched by 2 researchers, and randomized controlled trials that compared epidural labor analgesia utilizing LCLAs with nonepidural analgesia were retrieved. The primary outcomes were the duration of the second stage of labor and the instrumental birth rate; secondary outcomes included the cesarean delivery rate, the spontaneous vaginal delivery rate, and the duration of the first stage of labor. Ten studies (1809 women) were included. There was no significant difference between groups in the duration of the second stage of labor (mean difference = 5.71 minutes, 95% confidence interval [CI], -6.14 to 17.83; P = .36) or the instrumental birth rate (risk ratio [RR] = 1.52, 95% CI, 0.97-2.4; P = .07). There was no significant difference between groups in the cesarean delivery rate (RR = 0.8, 95% CI, 0.6-1.05; P = .11), the spontaneous vaginal delivery rate (RR = 0.98, 95% CI, 0.91-1.06; P = .62), or the duration of the first stage of labor (mean difference = 17.34 minutes, 95% CI, -5.89 to 40.56; P = .14). Compared with nonepidural analgesia, epidural analgesia with LCLAs is not associated with a prolonged duration of the second stage of labor or an increased instrumental birth rate. The results of this meta-analysis are based on small trials of low quality. These conclusions require confirmation by large-sample and high-quality trials in the future.

Comparison of the analgesic efficacy of ultrasound-guided rectus sheath block and local anesthetic infiltration for laparoscopic percutaneous extraperitoneal closure in children.

PubMed

Uchinami, Yuka; Sakuraya, Fumika; Tanaka, Nobuhiro; Hoshino, Koji; Mikami, Eri; Ishikawa, Taro; Fujii, Hitomi; Ishikawa, Takehiko; Morimoto, Yuji

2017-05-01

Ultrasound-guided rectus sheath block and local anesthetic infiltration are the standard options to improve postoperative pain for children undergoing surgery with a midline incision. However, there is no study comparing the effect of ultrasound-guided rectus sheath block with local anesthetic infiltration for children undergoing laparoscopic surgery. The aim of this trial was to compare the onset of ultrasound-guided rectus sheath block with that of local anesthetic infiltration for laparoscopic percutaneous extraperitoneal closure in children. We performed an observer-blinded, randomized, prospective trial. Enrolled patients were assigned to either an ultrasound-guided rectus sheath block group or a local anesthetic infiltration group. The ultrasound-guided rectus sheath block group (n = 17) received ultrasound-guided rectus sheath block with 0.2 ml·kg -1 of 0.375% ropivacaine per side in the posterior rectus sheath compartment. The local anesthetic infiltration group (n = 17) received local anesthetic infiltration with 0.2 ml·kg -1 of 0.75% ropivacaine. The Face, Legs, Activity, Cry, and Consolability (FLACC) pain scores were recorded at 0, 30, 60 min after arrival at the postanesthesia care unit. Of the 37 patients enrolled in this study, 34 completed the study protocol. A significant difference in the pain scale between the ultrasound-guided rectus sheath block group and local anesthetic infiltration group was found at 0 min (median: 0, interquartile range [IQR]: 0-1.5, vs median: 1, IQR 0-5, confidence interval of median [95% CI]: 0-3, P = 0.048), but no significant difference was found at 30 min (median: 1, IQR: 0-4 vs median: 6, IQR: 0-7, 95% CI: 0-5, P = 0.061), or 60 min (median: 0, IQR: 0-2 vs median: 1, IQR: 0-3, 95% CI: -1 to 1, P = 0.310). No significant difference was found in anesthesia time between the ultrasound-guided rectus sheath block and local anesthetic infiltration groups. No procedure-related complications were observed in either group

Local anesthetic infusion pump for pain management following open inguinal hernia repair: a meta-analysis.

PubMed

Wu, Chien-Chih; Bai, Chyi-Huey; Huang, Ming-Te; Wu, Chih-Hsiung; Tam, Ka-Wai

2014-01-01

Open inguinal hernia repair is one of the most painful procedures in day surgery. A continuous ambulatory analgesic is thought to reduce postoperative pain when it is applied to the surgical site. The aim of this study is to evaluate the efficacy of local anesthetic infusion pump following open inguinal hernia repair for the reduction of postoperative pain. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) that have investigated the outcomes of using an infusion pump for delivering a local anesthetic contrasted to a control group for open inguinal hernia repair. Pain was assessed from Day 1 to Day 5 following the surgery. The secondary outcomes included analgesia use and postoperative complications. We reviewed 5 trials that totaled 288 patients. The analgesic effects of bupivacaine (4 trials) and ropivacaine (one trial) were compared with a placebo group. The pooled mean difference in the score measuring the degree of pain diminished significantly at Day 1 to Day 4 in the experimental group. Two studies have reported that the number of analgesics required also decreased in the experimental group. No bupivacaine-related complication was reported. Our results revealed that applying a local anesthetic infusion pump following inguinal hernia repairs was more efficacious for reducing postoperative pain than a placebo. However, the findings were based on a small body of evidence in which methodological quality was not high. The potential benefits of applying a local anesthetic infusion pump to hernia repair must still be adequately investigated using further RCTs. Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

389 Allergic Reactions to Local Anesthetics: Detection by Skin Tests and Subcutaneous Provocation. Analysis of 160 Cases

PubMed Central

Arcanjo, Luiz; Gonçalves Tavares, Tania Maria; Delcourt, Nathalia; Baroni, Juliana; Rios, João; Rios, José Luiz

2012-01-01

Background Adverse reactions to local anesthetics (LA) are frequent and often referred to as allergic. Although immune-mediated reactions are rare, it should be investigated for suspected cases. The objective of this study was to determine the frequency of positive skin test to these drugs in patients with a suspected history of allergic reactions and describe the main socio-demographic characteristics of these individuals. Methods Retrospective study of medical records of patients attended at Policlínica Geral do Rio de Janeiro Allergic Clinic, between 2008 and 2011. The parameters evaluated were the test indication and the patient ages and gender. The drug tested was that the patient had a history of suspicion. Patients underwent skin prick and intradermal tests and subcutaneous provocation. Descriptive statistical analysis of the data was performed. Results It was performed 160 tests (125 female). Three of this total was excluded due to inconclusive results. In women, the highest proportion of tests was in the age group from 41 to 60 years (43%), while in males the higher concentration was at a youngest age group: 21 to 40 years (41%). The most common indication (103 cases, 65%) for the tests was a previous suspected anaphylactic reaction by LA. Seven of 157 tests had a positive result (4.4%), 6 of them occurred in women (4.8%). Only one test resulted in a type of anaphylactic reaction response (0.67%). All patients who presented positive response to the test had a history of per-anesthetic reaction that suggested an immune-mediated mechanism. Conclusions In patients with a history of previous reaction to local anesthetics, the skin tests with these drugs have a key role in the prevention of anaphylaxis, and on guidance for adequate anesthetic procedures.

Complex regional pain syndrome (CRPS) with resistance to local anesthetic block: a case report.

PubMed

Maneksha, F R; Mirza, H; Poppers, P J

2000-02-01

We present a case of complex regional pain syndrome (CRPS) Type 1 in a 12-year-old girl. The patient did not respond to the usual therapeutic modalities used to treat CRPS, including physical therapy, lumbar sympathetic block, epidural local anesthetic block, intravenous lidocaine infusion, or other oral medications. Of note is the fact that, during epidural block, the patient demonstrated a resistance to local anesthetic neural blockade in the area of the body involved with the pain problem. The mechanism of this resistance could be related to the changes in the dorsal horn cells of the spinal cord, secondary to activation of N-methyl-D-aspartate receptors, which may play a role in the pathophysiology of this pain syndrome.

Mass-spectrometric monitoring of the intravenous anesthetic concentration in the breathing circuit of an anesthesia machine

NASA Astrophysics Data System (ADS)

Elizarov, A. Yu.; Levshankov, A. I.

2011-04-01

Interaction between inhalational anesthetic sevoflurane and an absorber of CO2 (soda lime) in the breathing circuit of an anesthesia machine during low-flow anesthesia (0.5 l of a fresh gaseous mixture per minute) is studied with the mass-spectrometric method. Monitoring data for the concentration of sevoflurane and three toxic products of sevoflurane decompositions (substances A, B, and C) during anesthesia in the inspiration-expiration regime are presented. The highest concentration of substance A is found to be 65 ppm. The biochemical blood analysis before and after anesthesia shows that nephropathy is related to the function of liver toxicity. It is found that inhalational anesthetic sevoflurane influences the concentration of intravenous hypnotic propofol in blood.

Comparison of the efficacy of saline, local anesthetics, and steroids in epidural and facet joint injections for the management of spinal pain: A systematic review of randomized controlled trials

PubMed Central

Manchikanti, Laxmaiah; Nampiaparampil, Devi E.; Manchikanti, Kavita N.; Falco, Frank J.E.; Singh, Vijay; Benyamin, Ramsin M.; Kaye, Alan D.; Sehgal, Nalini; Soin, Amol; Simopoulos, Thomas T.; Bakshi, Sanjay; Gharibo, Christopher G.; Gilligan, Christopher J.; Hirsch, Joshua A.

2015-01-01

Background: The efficacy of epidural and facet joint injections has been assessed utilizing multiple solutions including saline, local anesthetic, steroids, and others. The responses to these various solutions have been variable and have not been systematically assessed with long-term follow-ups. Methods: Randomized trials utilizing a true active control design were included. The primary outcome measure was pain relief and the secondary outcome measure was functional improvement. The quality of each individual article was assessed by Cochrane review criteria, as well as the criteria developed by the American Society of Interventional Pain Physicians (ASIPP) for assessing interventional techniques. An evidence analysis was conducted based on the qualitative level of evidence (Level I to IV). Results: A total of 31 trials met the inclusion criteria. There was Level I evidence that local anesthetic with steroids was effective in managing chronic spinal pain based on multiple high-quality randomized controlled trials. The evidence also showed that local anesthetic with steroids and local anesthetic alone were equally effective except in disc herniation, where the superiority of local anesthetic with steroids was demonstrated over local anesthetic alone. Conclusion: This systematic review showed equal efficacy for local anesthetic with steroids and local anesthetic alone in multiple spinal conditions except for disc herniation where the superiority of local anesthetic with steroids was seen over local anesthetic alone. PMID:26005584

Comparison of ultrasound-guided supraclavicular block according to the various volumes of local anesthetic

PubMed Central

Kim, Seok Kon; Kang, Bong Jin; Kwon, Min A; Song, Jae Gyok; Jeon, Soo Mi

2013-01-01

Background The ultrasound guidance in regional nerve blocks has recently been introduced and gaining popularity. Ultrasound-guided supraclavicular block has many advantages including the higher success rate, faster onset time, and fewer complications. The aim of this study was to examine the clinical data according to the varied volume of local anesthetics in the ultrasound-guided supraclavicular block. Methods One hundred twenty patients were randomized into four groups, according to the local anesthetic volume used: Group 35 (n = 30), Group 30 (n = 30), Group 25 (n = 30), and Group 20 (n = 30). Supraclavicular blocks were performed with 1% mepivacaine 35 ml, 30 ml, 25 ml, and 20 ml, respectively. The success rate, onset time, and complications were checked and evaluated. Results The success rate (66.7%) was lower in Group 20 than that of Group 35 (96.7%) (P < 0.05). The average onset times of Group 35, Group 30, Group 25, and Group 20 were 14.3 ± 6.9 min, 13.6 ± 4.5 min, 16.7 ± 4.6 min, and 16.5 ± 3.7 min, respectively. There were no significant differences. Horner's syndrome was higher in Group 35 (P < 0.05). Conclusions In conclusion, we achieved 90% success rate with 30 ml of 1% mepivacaine. Therefore, we suggest 30 ml of local anesthetic volume for ultrasound-guided supraclavicular block. PMID:23814648

Pharmacology, toxicology, and clinical use of new long acting local anesthetics, ropivacaine and levobupivacaine.

PubMed

Leone, Stefania; Di Cianni, Simone; Casati, Andrea; Fanelli, Guido

2008-08-01

Levobupivacaine and ropivacaine, two new long-acting local anesthetics, have been developed as an alternative to bupivacaine, after the evidence of its severe toxicity. Both of these agents are pure left-isomers and, due to their three-dimensional structure, seem to have less toxic effects on the central nervous system and on the cardiovascular system. Many clinical studies have investigated their toxicology and clinical profiles: theoretically and experimentally, some differences have been observed, but the effects of these properties on clinical practice have not been shown. By examining randomised, controlled trials that have compared these three local agents, this review supports the evidence that both levobupivacaine and ropivacaine have a clinical profile similar to that of racemic bupivacaine, and that the minimal differences reported between the three anesthetics are mainly related to the slightly different anesthetic potency, with racemic bupivacaine > levobupivacaine > ropivacaine. However, the reduced toxic potential of the two pure left-isomers suggests their use in the clinical situations in which the risk of systemic toxicity related to either overdosing or unintended intravascular injection is high, such as during epidural or peripheral nerve blocks.

Ultrasound-guided continuous interscalene block: the influence of local anesthetic background delivery method on postoperative analgesia after shoulder surgery: a randomized trial.

PubMed

Hamdani, Mehdi; Chassot, Olivier; Fournier, Roxane

2014-01-01

Automated bolus delivery has recently been shown to reduce local anesthetic consumption and improve analgesia, compared with continuous infusion, in continuous sciatic and epidural block. However, there are few data on the influence of local anesthetic delivery method on local anesthetic consumption following interscalene blockade. This randomized, double-blind trial was designed to determine whether hourly automated perineural boluses (4 mL) of local anesthesia delivered with patient-controlled pro re nata (PRN, on demand) boluses would result in a reduction in total local anesthesia consumption during continuous interscalene blockade after shoulder surgery compared with continuous perineural infusion (4 mL/h) plus patient-controlled PRN boluses. One hundred one patients undergoing major shoulder surgery under general anesthesia with ultrasound-guided continuous interscalene block were randomly assigned to receive 0.2% ropivacaine via interscalene end-hole catheter either by continuous infusion 4 mL/h (n = 50) or as automated bolus 4 mL/h (n = 51). Both delivery methods were combined with 5 mL PRN boluses of 0.2% ropivacaine with a lockout time of 30 minutes. Postoperative number of PRN boluses, 24- and 48-hour local anesthetic consumption, pain scores, rescue analgesia (morphine), and adverse events were recorded. There were no significant differences in either the number of PRN ropivacaine boluses or total 48 hour local anesthetic consumption between the groups (18.5 [11-25.2] PRN boluses in the continuous infusion group vs 17 [8.5-29] PRN boluses in the automated bolus group). Postoperative pain was similar in both groups; on day 2, the median average pain score was 4 (2-6) in the continuous infusion group versus 3 (2-5) in the automated bolus group (P = 0.54). Nor were any statistically significant intergroup differences observed with respect to morphine rescue, incidence of adverse events, or patient satisfaction. In continuous interscalene blockade under

Local anesthetic lidocaine inhibits TRPM7 current and TRPM7-mediated zinc toxicity.

PubMed

Leng, Tian-Dong; Lin, Jun; Sun, Hua-Wei; Zeng, Zhao; O'Bryant, Zaven; Inoue, Koichi; Xiong, Zhi-Gang

2015-01-01

Previous study demonstrated that overstimulation of TRPM7 substantially contributes to zinc-mediated neuronal toxicity. Inhibition of TRPM7 activity and TRPM7-mediated intracellular Zn(2+) accumulation may represent a promising strategy in the treatment of stroke. To investigate whether local anesthetics lidocaine could inhibit TRPM7 channel and TRPM7-mediated zinc toxicity. Whole-cell patch-clamp technique was used to investigate the effect of local anesthetics on TRPM7 currents in cultured mouse cortical neurons and TRPM7-overexpressed HEK293 cells. Fluorescent Zn(2+) imaging technique was used to study the effect of lidocaine on TRPM7-mediated intracellular Zn(2+) accumulation. TRPM7-mediated zinc toxicity in neurons was used to evaluate the neuroprotective effect of lidocaine. (1) Lidocaine dose dependently inhibits TRPM7-like currents, with an IC50 of 11.55 and 11.06 mM in cultured mouse cortical neurons and TRPM7-overexpressed HEK293 cells, respectively; (2) Lidocaine inhibits TRPM7 currents in a use/frequency-dependent manner; (3) Lidocaine inhibits TRPM7-mediated intracellular Zn(2+) accumulation in both cortical neurons and TRPM7-overexpressed HEK293 cells; (4) TRPM7-mediated Zn(2+) toxicity is ameliorated by lidocaine in cortical neurons; (5) QX-314 has a similar inhibitory effect as lidocaine on TRPM7 currents when applied extracellularly; (6) Procaine also shows potent inhibitory effect on the TRPM7 currents in cortical neurons. Our data provide the first evidence that local anesthetic lidocaine inhibits TRPM7 channel and TRPM7-mediated zinc toxicity. © 2014 John Wiley & Sons Ltd.

The relationship between serum progesterone concentration and anesthetic and analgesic requirements: a prospective observational study of parturients undergoing cesarean delivery.

PubMed

Lee, Jeongwoo; Lee, Junho; Ko, Seonghoon

2014-10-01

In clinical practice, pregnant women have lower anesthetic requirements for general anesthesia than nonpregnant women. Although the hormonal changes such as progesterone associated with pregnancy may affect the minimum alveolar concentration of volatile anesthetics, the relationship between the anesthetic or analgesic requirements and progesterone level in full-term women has not been studied. In this study, we attempted to identify relationships between anesthetic or analgesic requirements and maternal serum concentrations of progesterone. We studied 100 parturients >36 weeks' gestation who were scheduled for planned cesarean delivery under general anesthesia. Venous blood was collected to measure the maternal progesterone concentration. Anesthesia was induced with 4 to 5 mg/kg thiopental and 0.8 mg/kg rocuronium. During anesthetic maintenance, sevoflurane 0.5% to 2.0% and nitrous oxide 50% in oxygen were titrated based on arterial blood pressure, heart rate, and bispectral index value. Vital signs, bispectral index, end-tidal sevoflurane concentration, and sevoflurane consumption per hour were recorded. Visual analog scale pain scores and cumulative analgesic consumption were recorded at 2, 24, and 48 hours postoperatively. The mean serum progesterone concentration was 128.2 ± 83.0 ng/mL. There was a significant negative correlation between sevoflurane consumption per hour and serum progesterone concentration (Pearson correlation r = -0.26; 95% confidence interval, -0.44 to -0.05, P = 0.01). Cumulative analgesic consumption at postoperative hours 2 (r = -0.20, P = 0.05), 24 (r = -0.25, P = 0.02), and 48 (r = -0.28, P = 0.01) were correlated inversely with serum progesterone concentration. Women with high progesterone levels (higher than the median value) had lower sevoflurane consumption per hour (P = 0.02) and 48-hour postoperative cumulative analgesic consumption (P = 0.02) than women with low (below the median value) levels. The decreased anesthetic and

Evaluation of local anesthetic effects of Lidocaine-Ibuprofen ionic liquid stabilized silver nanoparticles in Male Swiss mice.

PubMed

Jiang, Qiliang; Yu, Shashuang; Li, Xingwang; Ma, Chuangen; Li, Aixiang

2018-01-01

A simple approach for the synthesis of Lidocaine-Ibuprofen ionic liquid stabilized silver nanoparticles (IL-AgNPs) was reported in this work. The shape, size and surface morphology of the Lidocaine-Ibuprofen ionic liquid stabilized AgNPs were characterized by using spectroscopic and microscopic techniques such as Ultraviolet-visible spectroscopy (UV-Visible), X-ray diffraction (XRD) analysis, Selected area electron diffraction (SAED), Transmission electron microscopy (TEM). TEM analysis showed the formation of 20-30nm size of IL-AgNPs with very clear lattice fringes. SAED pattern confirmed the highly crystalline nature of fabricated IL stabilized AgNPs. EDS results confirmed the formation of nanosilver. The fabricated IL-AgNPs were studied for their local anesthetic effect in rats. The results of local anesthetic effect showed that the time for onset of action by IL-AgNPs is 10min, which is significantly higher than that for EMLA. Further, tactile test results confirmed the stronger and faster local anesthetic effect of IL-AgNPs when compared to that of EMLA. Copyright © 2017. Published by Elsevier B.V.

Dexmedetomidine Dose Dependently Enhances the Local Anesthetic Action of Lidocaine in Inferior Alveolar Nerve Block: A Randomized Double-Blind Study.

PubMed

Ouchi, Kentaro; Sugiyama, Kazuna

2016-01-01

Dexmedetomidine (DEX) dose dependently enhances the local anesthetic action of lidocaine in rats. We hypothesized that the effect might also be dose dependent in humans. We evaluated the effect of various concentrations of DEX with a local anesthetic in humans. Eighteen healthy volunteers were randomly assigned by a computer to receive 1.8 mL of 1 of 4 drug combinations: (1) 1% lidocaine with 2.5 ppm (parts per million) (4.5 μg) DEX, (2) lidocaine with 5.0 ppm (9.0 μg) DEX, (3) lidocaine with 7.5 ppm (13.5μg) DEX, or (4) lidocaine with 1:80,000 (22.5 μg) adrenaline (AD), to produce inferior alveolar nerve block. Pulp latency and lower lip numbness (for assessing onset and duration of anesthesia) were tested, and sedation level, blood pressure, and heart rate were recorded every 5 minutes for 20 minutes, and every 10 minutes from 20 to 60 minutes. Pulp latency of each tooth increased compared with baseline, from 5 to 15 minutes until 60 minutes. There were no significant intergroup differences at any time point. Anesthesia onset was not different between groups. Anesthesia duration was different between groups (that with DEX 7.5 ppm was significantly longer than that with DEX 2.5 ppm and AD; there was no difference between DEX 2.5 ppm and AD). Blood pressure decreased from baseline in the 5.0 and 7.5 ppm DEX groups at 30 to 60 minutes, although there was no hypotension; moreover, heart rate did not change in any group. Sedation score did not indicate deep sedation in any of the groups. Dexmedetomidine dose dependently enhances the local anesthetic action of lidocaine in humans. Dexmedetomidine at 2.5 ppm produces similar enhancement of local anesthesia effect as addition of 1:80,000 AD.

Benzocaine as an anesthetic for striped bass

USGS Publications Warehouse

Gilderhus, Philip A.; Lemm, Carol A.; Woods, L. Curry

1991-01-01

Benzocaine was tested as an anesthetic on juvenile and mature adult striped bass (Morone saxatilis ). Concentrations of 55 mg/L at 22 degree C to 80 mg/L at 11 degree C effectively anesthetized fish in about 3 min. Recovery was more rapid as temperature increased. Fish survived concentrations of twice the effective concentration and exposure times up to 60 min at the effective concentration. Striped bass required higher concentrations for anesthetization than had been previously demonstrated for salmonid fishes, but safety margins for both concentration and exposure time were wider than for the salmonids.

Extended release local anesthetic agents in a postoperative arthritic pain model.

PubMed

Ickowicz, Diana E; Golovanevski, Ludmila; Haze, Amir; Domb, Abraham J; Weiniger, Carolyn F

2014-01-01

Local anesthetics play an important role in postoperative pain management in orthopedic joint procedures. The aim of this study was to determine the effect of an intraoperative extra-articular injection of poly(DL-lactic acid co castor oil 3:7), p(DLLA:CO) 3:7 loaded with 15% bupivacaine, for postoperative analgesia following knee arthroplasty. Prolonged release local anesthetic formulation was synthesized by mixing p(DLLA:CO) 3:7 with bupivacaine base. Under anesthesia, the knee joint of Sprague-Dawley rats was exposed, a hole drilled in the femoral trochlea. 0.2 mL of either 15% polymer-bupivacaine formulation or plain bupivacaine (control) was injected locally and compared with a nonsurgery control group. Mechanical hyperalgesia was determined by counting the vocalizations and leg withdrawal after joint squeezing. Behavioral assessments over a day postoperative period revealed a reduction in rearing and ambulation in an open-field apparatus in animals of both experimental groups compared with the nonsurgery control. The vocalizations during the hyperalgesia test increased compared with the control at 24 h. At 48 h, 3.667 ± 0.5138, p = 0.0076 vocalizations were recorded for the plain bupivacaine group versus 1.417 ± 0.5138, p < 0.0001 in the 15% polymer-bupivacaine formulation. Bupivacaine encapsulated in p(DLLA:CO) 3:7 extended the duration of the analgesia compared with plain drug in rats and could represent effective postoperative analgesic in orthopedic joint procedures. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

Minimum anesthetic volume in regional anesthesia by using ultrasound-guidance.

PubMed

Di Filippo, Alessandro; Falsini, Silvia; Adembri, Chiara

2016-01-01

The ultrasound guidance in regional anesthesia ensures the visualization of needle placement and the spread of Local Anesthetics. Over the past few years there was a substantial interest in determining the Minimum Effective Anesthetic Volume necessary to accomplish surgical anesthesia. The precise and real-time visualization of Local Anesthetics spread under ultrasound guidance block may represent the best requisite for reducing Local Anesthetics dose and Local Anesthetics-related effects. We will report a series of studies that have demonstrated the efficacy of ultrasound guidance blocks to reduce Local Anesthetics and obtain surgical anesthesia as compared to block performed under blind or electrical nerve stimulation technique. Unfortunately, the results of studies are widely divergent and not seem to indicate a dose considered effective, for each block, in a definitive way; but it is true that, through the use of ultrasound guidance, it is possible to reduce the dose of anesthetic in the performance of anesthetic blocks. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

Activation of TRPA1 by membrane permeable local anesthetics

PubMed Central

2011-01-01

Background Low concentrations of local anesthetics (LAs) suppress cellular excitability by inhibiting voltage-gated Na+ channels. In contrast, LAs at high concentrations can be excitatory and neurotoxic. We recently demonstrated that LA-evoked activation of sensory neurons is mediated by the capsaicin receptor TRPV1, and, to a lesser extent by the irritant receptor TRPA1. LA-induced activation and sensitization of TRPV1 involves a domain that is similar, but not identical to the vanilloid-binding domain. Additionally, activation of TRPV1 by LAs involves PLC and PI(4,5)P2-signalling. In the present study we aimed to characterize essential structural determinants for LA-evoked activation of TRPA1. Results Recombinant rodent and human TRPA1 were expressed in HEK293t cells and investigated by means of whole-cell patch clamp recordings. The LA lidocaine activates TRPA1 in a concentration-dependent manner. The membrane impermeable lidocaine-derivative QX-314 is inactive when applied extracellularly. Lidocaine-activated TRPA1-currents are blocked by the TRPA1-antagonist HC-030031. Lidocaine is also an inhibitor of TRPA1, an effect that is more obvious in rodent than in human TRPA1. This species-specific difference is linked to the pore region (transmembrane domain 5 and 6) as described for activation of TRPA1 by menthol. Unlike menthol-sensitivity however, lidocaine-sensitivity is not similarly determined by serine- and threonine-residues within TM5. Instead, intracellular cysteine residues known to be covalently bound by reactive TRPA1-agonists seem to mediate activation of TRPA1 by LAs. Conclusions The structural determinants involved in activation of TRPA1 by LAs are disparate from those involved in activation by menthol or those involved in activation of TRPV1 by LAs. PMID:21861907

The pH-dependent rate of action of local anesthetics on the node of Ranvier

PubMed Central

1977-01-01

Local anesthetic solutions were applied suddenly to the outside of single myelinated nerve fibers to measure the time course of development of block of sodium channels. Sodium currents were measured under voltage clamp with test pulses applied several times per second during the solution change. The rate of block was studied by using drugs of different lipid solubility and of different charge type, and the external pH was varied from pH 8.3 to pH 6 to change the degree of ionization of the amine compounds. At pH 8.3 the half-time of action of amine anesthetics such as lidocaine, procaine, tetracaine, and others was always less than 2 s and usually less than 1 s. Lowering the pH to 6.0 decreased the apparent potency and slowed the rate of action of these drugs. The rate of action of neutral benzocaine was fast (1 s) and pH independent. The rate of action of cationic quaternary QX-572 was slow (greater than 200 s) and also pH independent. Other quaternary anesthetic derivatives showed no action when applied outside. The result is that neutral drug forms act much more rapidly than charged ones, suggesting that externally applied local anesthetics must cross a hydrophobic barrier to reach their receptor. A model representing diffusion of drug into the nerve fiber gives reasonable time courses of action and reasonable membrane permeability coefficients on the assumption that the hydrophobic barrier is the nodal membrane. Arguments are given that there may be a need for reinterpretation of many published experiments on the location of the anesthetic receptor and on which charge form of the drug is active to take into account the effects of unstirred layers, high membrane permeability, and high lipid solubility. PMID:16078

Preparation and characterization of poly(ε-caprolactone) nanospheres containing the local anesthetic lidocaine.

PubMed

Ramos Campos, Estefânia Vangelie; Silva de Melo, Nathalie Ferreira; Guilherme, Viviane Aparecida; de Paula, Eneida; Rosa, André Henrique; de Araújo, Daniele Ribeiro; Fraceto, Leonardo Fernandes

2013-01-01

The objective of this work was to develop a modified release system for the local anesthetic lidocaine (LDC), using poly(ε-caprolactone) (PCL) nanospheres (NSs), to improve the pharmacological properties of the drug when administered by the infiltration route. In vitro experiments were used to characterize the system and investigate the release mechanism. The NSs presented a polydispersion index of 0.072, an average diameter of 449.6 nm, a zeta potential of -20.1 mV, and an association efficiency of 93.3%. The release profiles showed that the release of associated LDC was slower than that of the free drug. Atomic force microscopy analyses showed that the spherical structure of the particles was preserved as a function of time, as well as after the release experiments. Cytotoxicity and pharmacological tests confirmed that association with the NSs reduced the toxicity of LDC, and prolonged its anesthetic action. This new formulation could potentially be used in applications requiring gradual anesthetic release, especially dental procedures. Copyright © 2012 Wiley Periodicals, Inc.

Relief of Injection Pain During Delivery of Local Anesthesia by Computer-Controlled Anesthetic Delivery System for Periodontal Surgery: Randomized Clinical Controlled Trial.

PubMed

Chang, Hyeyoon; Noh, Jiyoung; Lee, Jungwon; Kim, Sungtae; Koo, Ki-Tae; Kim, Tae-Il; Seol, Yang-Jo; Lee, Yong-Moo; Ku, Young; Rhyu, In-Chul

2016-07-01

Pain from local anesthetic injection makes patients anxious when visiting a dental clinic. This study aims to determine differences in pain according to types of local anesthetizing methods and to identify the possible contributing factors (e.g., dental anxiety, stress, and sex). Thirty-one patients who underwent open-flap debridement in maxillary premolar and molar areas during treatment for chronic periodontitis were evaluated for this study. A randomized, split-mouth, single-masked clinical trial was implemented. The dental anxiety scale (DAS) and perceived stress scale (PSS) were administered before surgery. Two lidocaine ampules for each patient were used for local infiltration anesthesia (supraperiosteal injection). Injection pain was measured immediately after local infiltration anesthesia using the visual analog pain scale (VAS) questionnaire. Results from the questionnaire were used to assess degree of pain patients feel when a conventional local anesthetic technique (CNV) is used compared with a computer-controlled anesthetic delivery system (CNR). DAS and PSS did not correlate to injection pain. VAS scores were lower for CNR than for CNV regardless of the order in which anesthetic procedures were applied. VAS score did not differ significantly with sex. Pearson coefficient for correlation between VAS scores for the two procedures was 0.80, also indicating a strong correlation. Within the limitations of the present study, relief from injection pain is observed using CNR.

Vapor Pressures of Anesthetic Agents at Temperatures below Zero Degrees Celsius and a Novel Anesthetic Delivery Device

PubMed Central

Schenning, Katie J.; Casson, Henry; Click, Sarah V.; Brambrink, Lucas; Chatkupt, Thomas T.; Alkayed, Nabil J.; Hutchens, Michael P.

2016-01-01

At room temperature, the vapor pressures of desflurane, isoflurane, and sevoflurane are well above the clinically useful range. We hypothesized that therapeutic concentrations of these agents could be achieved at temperatures below zero, but the vapor pressure-temperature relationship is unknown below zero. Secondarily, we hypothesized that this relationship could be exploited to deliver therapeutic-range concentrations of anesthetic vapor. We therefore set out to determine the low temperature-vapor pressure relationships of each anesthetic agent thereby identifying the saturated vapor concentration of each agent at any temperature below zero. To test our hypothesis, we measured the saturated vapor concentration at 1 atmosphere of pressure for temperatures between -60°C and 0°C thus developing an empiric relationship for each agent. There was consistency in repeated experiments for all three agents. To test the empiric data we constructed a digitally-controlled thermoelectric anesthetic vaporizer, characterized the device, and used it to deliver anesthetic vapor to laboratory mice. We report, for the first time, the temperature-vapor pressure relationship at temperatures below 0°C for desflurane, isoflurane, and sevoflurane as well as the TMAC of these agents: the temperature at which the vapor pressure is equal to the minimum alveolar concentration. We describe the construction and limited validation of an anesthetic vaporizer prototype based on this principle. We conclude that clinically relevant concentrations of volatile anesthetics may be achieved at low temperatures. PMID:27632346

Vapor Pressures of Anesthetic Agents at Temperatures Below 0°C and a Novel Anesthetic Delivery Device.

PubMed

Schenning, Katie J; Casson, Henry; Click, Sarah V; Brambrink, Lucas; Chatkupt, Thomas T; Alkayed, Nabil J; Hutchens, Michael P

2017-02-01

At room temperature, the vapor pressures of desflurane, isoflurane, and sevoflurane are well above the clinically useful range. We hypothesized that therapeutic concentrations of these agents could be achieved at temperatures below 0°C, but the vapor pressure-temperature relationship is unknown below 0. Second, we hypothesized that this relationship could be exploited to deliver therapeutic-range concentrations of anesthetic vapor. We therefore set out to determine the low temperature-vapor pressure relationships of each anesthetic agent, thereby identifying the saturated vapor concentration of each agent at any temperature below 0°C. To test our hypothesis, we measured the saturated vapor concentration at 1 atm of pressure for temperatures between -60 and 0°C, thus developing an empiric relationship for each agent. There was consistency in repeated experiments for all 3 agents. To test the empiric data, we constructed a digitally controlled thermoelectric anesthetic vaporizer, characterized the device, and used it to deliver anesthetic vapor to laboratory mice. We report, for the first time, the temperature-vapor pressure relationship at temperatures below 0°C for desflurane, isoflurane, and sevoflurane as well as the TMAC of these agents: the temperature at which the vapor pressure is equal to the minimum alveolar concentration. We describe the construction and limited validation of an anesthetic vaporizer prototype on the basis of this principle. We conclude that clinically relevant concentrations of volatile anesthetics may be achieved at low temperatures.

Can we use lower volume of local anesthetic for infraclavicular brachial plexus nerve block under ultrasound guidance in children?

PubMed

Ince, Ilker; Aksoy, Mehmet; Dostbil, Aysenur; Tuncer, Kutsi

2017-09-01

To determine if the infraclavicular brachial plexus block can be applied with lower volume of local anesthetic. Randomised, double-blinded clinical trial. 60 patients aged 5-15years with ASA I-II who underwent emergent or elective arm, forearm or hand operations were included in the study. Patients were divided into two groups randomly; standard volume local anesthetic administered group (Group S, n=30) and low volume anesthetic administered group (Group L, n=30). Postoperative pain scores, sensory and motor block durations were noted. Pain scores (Wong-Baker Face Scale) were evaluated and the results were detected to be similar at all times (30min, 1, 2, 4, 8, 12, 24h). Durations of motor block were 168(±16) minutes and 268(±15) minutes in Group L and Group S respectively and the difference was statistically significant (p<0.001). Durations of sensory block were 385(±26) and 402(±39) in Group L and Group S respectively and no statistically significant difference was detected (p=0.064). Similar block success, postoperative sensory block durations and pain scores could be obtained during infraclavicular brachial plexus in pediatric patients with lower local anesthetic volumes. Copyright © 2016 Elsevier Inc. All rights reserved.

From micro- to nanostructured implantable device for local anesthetic delivery

PubMed Central

Zorzetto, Laura; Brambilla, Paola; Marcello, Elena; Bloise, Nora; De Gregori, Manuela; Cobianchi, Lorenzo; Peloso, Andrea; Allegri, Massimo; Visai, Livia; Petrini, Paola

2016-01-01

Local anesthetics block the transmission of painful stimuli to the brain by acting on ion channels of nociceptor fibers, and find application in the management of acute and chronic pain. Despite the key role they play in modern medicine, their cardio and neurotoxicity (together with their short half-life) stress the need for developing implantable devices for tailored local drug release, with the aim of counterbalancing their side effects and prolonging their pharmacological activity. This review discusses the evolution of the physical forms of local anesthetic delivery systems during the past decades. Depending on the use of different biocompatible materials (degradable polyesters, thermosensitive hydrogels, and liposomes and hydrogels from natural polymers) and manufacturing processes, these systems can be classified as films or micro- or nanostructured devices. We analyze and summarize the production techniques according to this classification, focusing on their relative advantages and disadvantages. The most relevant trend reported in this work highlights the effort of moving from microstructured to nanostructured systems, with the aim of reaching a scale comparable to the biological environment. Improved intracellular penetration compared to microstructured systems, indeed, provides specific drug absorption into the targeted tissue and can lead to an enhancement of its bioavailability and retention time. Nanostructured systems are realized by the modification of existing manufacturing processes (interfacial deposition and nanoprecipitation for degradable polyester particles and high- or low-temperature homogenization for liposomes) or development of novel strategies (electrospun matrices and nanogels). The high surface-to-volume ratio that characterizes nanostructured devices often leads to a burst drug release. This drawback needs to be addressed to fully exploit the advantage of the interaction between the target tissues and the drug: possible strategies

Ultrasound assessment of cranial spread during caudal blockade in children: Effect of different volumes of local anesthetic

PubMed Central

Sinha, Chandni; Kumar, Amarjeet; Sharma, Shalini; Singh, Akhilesh Kumar; Majumdar, Somak; Kumar, Ajeet; Sahay, Nishant; Kumar, Bindey; Bhadani, UK

2017-01-01

Background: Ultrasound-guided caudal block injection is a simple, safe, and effective method of anesthesia/analgesia in pediatric patients. The volume of caudal drug required has always been a matter of debate. Materials and Methods: This present prospective, randomized, double-blinded study aimed to measure extent of the cranial spread of caudally administered levobupivacaine in Indian children by means of real-time ultrasonography. Ninety American Society of Anesthesiologists I/II children scheduled for urogenital surgeries were enrolled in this trial. Anesthesia and caudal analgesia were administered in a standardized manner in the patients. The patients received 0.5 ml/kg or 1 ml/kg or 1.25 ml/kg of 0.125% levobupivacaine according to the group allocated. Cranial spread of local anesthetic was noted using ultrasound. Results: There was no difference in the spread when related to age, sex, weight, or body mass index. A significant difference of ultrasound-assessed cranial spread of the local anesthetic was found between Group 1 (0.5 ml/kg) with both Group 2 (1 ml/kg) (P = 0.001) and with Group 3 (1.125 ml/kg) (P < 0.001) but there is no significant difference between Group 2 and Group 3 (P = 0.451) revealing that spinal level spread is only different between 0.5 ml/kg and 1 ml/kg of local anesthetic. Conclusion: In conclusion, the ultrasound assessment of local anesthetic spread after a caudal block showed that cranial spread of the block is dependent on the volume injected into the caudal space. Since there was no difference between 1 ml/kg and 1.25 ml/kg, to achieve a dermatomal blockade up to thoracic level, we might have to increase the dose beyond 1.25 ml/kg, keeping the toxic dose in mind. PMID:29033727

Effect of local anesthetic dilution on the onset time and duration of double-injection sciatic nerve block: a prospective, randomized, blinded evaluation.

PubMed

Cappelleri, Gianluca; Ambrosoli, Andrea Luigi; Turconi, Stefania; Gemma, Marco; Ricci, Erika Basso; Cornaggia, Gabriele

2014-08-01

Among the various factors influencing the success rate, onset time, and duration of peripheral nerve blocks, the role of local anesthetics concentration remains uncertain. In this prospective, randomized, single-blinded study, we evaluated whether varying the dilution of a fixed dose of mepivacaine solution influenced onset time and duration of sciatic nerve block. Ninety ASA physical status I to II patients scheduled for foot surgery were randomly allocated to receive a double-injection Labat sciatic nerve block with 12 mL mepivacaine 2% (group concentration I = 45 patients) or 24 mL of mepivacaine 1% (group volume II = 45 patients). The nerve stimulator was initially set at 2 Hz, 0.1 millisecond, 1 mA. The total amount of local anesthetic (240 mg) was kept constant and equally divided between the peroneal and tibial nerves. All patients also received an ultrasound-guided popliteal sciatic nerve catheter for postoperative analgesia. Times to readiness for surgery, performance, and offset of local anesthetic were recorded. Our primary end point was to determine a possible difference in offset time between groups. Continuous variables were expressed as median (IQR) and compared with the Wilcoxon-Mann-Whitney U test; WMWodds are reported together with their 95% confidence interval. The overall success rate of sciatic nerve block was 99%. Time of performance was shorter in group I, 120 seconds (90-150 seconds), than that in group II, 150 seconds (120-180 seconds) (P = 0.0048; WMWodds 2.26 [1.35-4.34]). The onset time of sensory and motor sciatic nerve block was 4 minutes (2-9 minutes) in group I and 6 minutes (4-10 minutes) in group II (P = 0.41; WMWodds 1.21 [0.77-1.95]), while the duration of sensory block was 235 minutes (203-250 minutes) in group I, and 240 minutes (218-247 minutes) in group II respectively (P = 0.51; WMWodds 1.20 [0.69-2.16]). We found no evidence that varying volume and concentration while maintaining a fixed total dose of mepivacaine alters the

Development of Ultra Long Duration Local Anesthetic Agents in a Rat Model

DTIC Science & Technology

1994-02-24

this formulation is not toxic to the spinal cord. Initial trials with lecithin-coated bupivacaine microcrystals indic,-.. that this preparation also has...an ultra long duration local anesthetic effect, producing a 43 hour block in the rat tail. Clinical trials of this preparation in a human model are...l f _ _ _ Memorandum for LTC Dean E. Calcagni, M.D. Director, Combat Casualty Research Program USAMRDC Subject: Annual Report for Clinical

Efficacy of Benzocaine 20% Topical Anesthetic Compared to Placebo Prior to Administration of Local Anesthesia in the Oral Cavity: A Randomized Controlled Trial.

PubMed

de Freiras, Guilherme Camponogara; Pozzobon, Roselaine Terezinha; Blaya, Diego Segatto; Moreira, Carlos Heitor

2015-01-01

The aim of the present study was to compare the effects of a topical anesthetic to a placebo on pain perception during administration of local anesthesia in 2 regions of the oral cavity. A split-mouth, double-blind, randomized clinical trial design was used. Thirty-eight subjects, ages 18-50 years, American Society of Anesthesiologists I and II, received 4 anesthetic injections each in regions corresponding to the posterior superior alveolar nerve (PSA) and greater palatine nerve (GPN), totaling 152 sites analyzed. The side of the mouth where the topical anesthetic (benzocaine 20%) or the placebo was to be applied was chosen by a flip of a coin. The needle used was 27G, and the anesthetic used for administration of local anesthesia was 2% lidocaine with 1:100,000 epinephrine. After receiving the administration of local anesthesia, each patient reported pain perception on a visual analog scale (VAS) of 100-mm length. The results showed that the topical anesthetic and the placebo had similar effects: there was no statistically significant VAS difference between the PSA and the GPN pain ratings. A higher value on the VAS for the anesthesia of the GPN, relative to the PSA, was observed for both groups. Regarding gender, male patients had higher values on the VAS compared with female patients, but these differences were not meaningful. The topical anesthetic and the placebo had similar effects on pain perception for injection of local anesthesia for the PSA and GPN.

Efficacy of Benzocaine 20% Topical Anesthetic Compared to Placebo Prior to Administration of Local Anesthesia in the Oral Cavity: A Randomized Controlled Trial

PubMed Central

de Freiras, Guilherme Camponogara; Pozzobon, Roselaine Terezinha; Blaya, Diego Segatto; Moreira, Carlos Heitor

2015-01-01

The aim of the present study was to compare the effects of a topical anesthetic to a placebo on pain perception during administration of local anesthesia in 2 regions of the oral cavity. A split-mouth, double-blind, randomized clinical trial design was used. Thirty-eight subjects, ages 18–50 years, American Society of Anesthesiologists I and II, received 4 anesthetic injections each in regions corresponding to the posterior superior alveolar nerve (PSA) and greater palatine nerve (GPN), totaling 152 sites analyzed. The side of the mouth where the topical anesthetic (benzocaine 20%) or the placebo was to be applied was chosen by a flip of a coin. The needle used was 27G, and the anesthetic used for administration of local anesthesia was 2% lidocaine with 1:100,000 epinephrine. After receiving the administration of local anesthesia, each patient reported pain perception on a visual analog scale (VAS) of 100-mm length. The results showed that the topical anesthetic and the placebo had similar effects: there was no statistically significant VAS difference between the PSA and the GPN pain ratings. A higher value on the VAS for the anesthesia of the GPN, relative to the PSA, was observed for both groups. Regarding gender, male patients had higher values on the VAS compared with female patients, but these differences were not meaningful. The topical anesthetic and the placebo had similar effects on pain perception for injection of local anesthesia for the PSA and GPN. PMID:26061572

A comparison of a refrigerant and a topical anesthetic gel as preinjection anesthetics: a clinical evaluation.

PubMed

Kosaraju, Amar; Vandewalle, Kraig S

2009-01-01

The authors used a split-mouth design to determine the effectiveness of a refrigerant compared with that of a topical anesthetic gel in reducing the pain experienced during a posterior palatal anesthetic injection. Sixteen participants received a five-second application of a refrigerant (1,1,1,3,3-pentafluoropropane/1,1,1,2-tetrafluoroethane) and a two-minute application of a topical anesthetic gel (20 percent benzocaine gel) in the posterior palatal area before an injection of a local anesthetic solution was administered with a 30-gauge needle. Participants rated the pain they experienced after each injection by using a 100-millimeter visual analog scale (VAS) with endpoints of "no pain" and "worst possible pain." The authors calculated VAS scores by measuring the distance in millimeters from the no pain end of the scale. They analyzed data with a paired t test (alpha = .05). The group receiving the refrigerant had a mean VAS score of 17.7 +/- 15.3 mm, and the group receiving the topical anesthetic gel had a VAS score of 26.2 +/- 18.0 mm. The use of the refrigerant compared with the use of topical anesthetic gel significantly reduced the pain experienced during administration of local anesthetic injections (P = .02). The use of a refrigerant as a preinjection anesthetic was more effective compared with the use of a topical anesthetic gel in reducing the pain experienced by participants who received a posterior palatal injection. The potential benefits of using a refrigerant rather than a topical anesthetic gel are pain reduction, decreased application time, ease of application and avoidance of displeasing taste.

Comparison of continuous interscalene block and subacromial infusion of local anesthetic for postoperative analgesia after open shoulder surgery.

PubMed

Baskan, Semih; Cankaya, Deniz; Unal, Hidayet; Yoldas, Burak; Taspinar, Vildan; Deveci, Alper; Tabak, Yalcin; Baydar, Mustafa

2017-01-01

This study compared the efficacy of continuous interscalene block (CISB) and subacromial infusion of local anesthetic (CSIA) for postoperative analgesia after open shoulder surgery. This randomized, prospective, double-blinded, single-center study included 40 adult patients undergoing open shoulder surgery. All patients received a standardized general anesthetic. The patients were separated into group CISB and group CSIA. A loading dose of 40 mL 0.25% bupivacaine was administered and patient-controlled analgesia was applied by catheter with 0.1% bupivacaine 5 mL/h throughout 24 h basal infusion, 2 mL bolus dose, and 20 min knocked time in both groups postoperatively. Visual analog scale (VAS) scores, additional analgesia need, local anesthetic consumption, complications, and side effects were recorded during the first 24 h postoperatively. The range of motion (ROM) score was recorded preoperatively and in the first and third weeks postoperatively. A statistically significant difference was determined between the groups in respect of consumption of local anesthetic, VAS scores, additional analgesia consumption, complications, and side effects, with lower values recorded in the CISB group. There were no significant differences in ROM scoring in the preoperative and postoperative third week between the two groups but there were significant differences in ROM scoring in the postoperative first week, with higher ROM scoring values in the group CISB patients. The results of this study have shown that continuous interscalene infusion of bupivacaine is an effective and safe method of postoperative analgesia after open shoulder surgery.

Local Anesthetic Activity from Extracts, Fractions and Pure Compounds from the Roots of Ottonia anisum Spreng. (Piperaceae).

PubMed

López, Kelvin S E; Marques, André M; Moreira, Davyson DE L; Velozo, Leosvaldo S; Sudo, Roberto T; Zapata-Sudo, Gisele; Guimarães, Elsie F; Kaplan, Maria Auxiliadora C

2016-01-01

Piperaceae species can be found worldwide in tropical and subtropical areas and many of them have been used for centuries in traditional folk medicine and in culinary. In Brazil, species of Piperaceae are commonly used in some communities as local anesthetic and analgesic. Countrified communities have known some species of the genus Ottonia as "anestesia" and it is a common habit of chewing leaves and roots of Ottonia species to relief toothache. The purpose of this study is to report our findings on new molecules entities obtained from the roots of Ottonia anisum Spreng, in which local anesthetic activity (sensory blockage) is demonstrated for the first time in vivo guinea pig model. Phytochemical investigation led to the isolation of three amides (pipercallosidine, piperine and valeramide) and in an enriched mixture of seven amides (valeramide, 4,5-dihydropiperlonguminine, N-isobutil-6-piperonil-2-hexenamide, piperovatine, dihydropipercallosidine, pipercallosidine and pipercallpsine). Our findings demonstrated the anesthetic potential for the methanolic extract from roots, its n-hexane partition and amides from O. anisum and it is in agreement with ethnobotanical survey.

Titration calorimetry of anesthetic-protein interaction: negative enthalpy of binding and anesthetic potency.

PubMed

Ueda, I; Yamanaka, M

1997-04-01

Anesthetic potency increases at lower temperatures. In contrast, the transfer enthalpy of volatile anesthetics from water to macromolecules is usually positive. The transfer decreases at lower temperature. It was proposed that a few selective proteins bind volatile anesthetics with negative delta H, and these proteins are involved in signal transduction. There has been no report on direct estimation of binding delta H of anesthetics to proteins. This study used isothermal titration calorimetry to analyze chloroform binding to bovine serum albumin. The calorimetrically measured delta H cal was -10.37 kJ.mol-1. Thus the negative delta H of anesthetic binding is not limited to signal transduction proteins. The binding was saturable following Fermi-Dirac statistics and is characterized by the Langmuir adsorption isotherms, which is interfacial. The high-affinity association constant, K, was 2150 +/- 132 M-1 (KD = 0.47 mM) with the maximum binding number, Bmax = 3.7 +/- 0.2. The low-affinity K was 189 +/- 3.8 M-1 (KD = 5.29 mM), with a Bmax of 13.2 +/- 0.3. Anesthetic potency is a function of the activity of anesthetic molecules, not the concentration. Because the sign of delta H determines the temperature dependence of distribution of anesthetic molecules, it is irrelevant to the temperature dependence of anesthetic potency.

Waste anesthetic gas exposures to veterinarians and animal technicians

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wingfield, W.E.; Ruby, D.L.; Buchan, R.M.

1981-02-15

A survey of veterinarians was conducted in an 11-county region of eastern Colorado to determine the extent of usage of inhalation anesthetics and to measure exposures of veterinarians and their assistants to waste anesthetic gases. The survey indicated that inhalation anesthetics were used in 80.8% of the 210 practices. Exposures to waste anesthetics in veterinary practices were far less than reported in human hospitals. Waste anesthetic concentrations were affected by size of the patient, type of breathing system, and use of scavenging systems. Dilution ventilation had no effect on breathing zone concentrations. The endotracheal tube and occasionally the anesthetic machinemore » were the major sources of leakage of anesthetic gases.« less

Drug interactions: volatile anesthetics and opioids.

PubMed

Glass, P S; Gan, T J; Howell, S; Ginsberg, B

1997-09-01

Multiple drugs are used to provide anesthesia. Volatile anesthetics are commonly combined with opioids. Several studies have demonstrated that small doses of opioid (i.e., within the analgesic range) result in a marked reduction in minimum alveolar concentration (MAC) of the volatile anesthetic that will prevent purposeful movement in 50% of patients at skin incision). Further increases in opioid dose provide only a further small reduction in MAC. Thus, a ceiling effect of the opioid is observed at a MAC value of the volatile anesthetic equal to its MAC awake. Recovery from anesthesia when an opioid is combined with a volatile anesthetic is dependent on the rate of decrease of both drugs to their respective concentrations that are associated with adequate spontaneous ventilation and awakening. Through an understanding of the pharmacodynamic interaction of volatile anesthetics with opioids and the pharmacokinetic processes responsible for the recovery from drug effect, optimal dosing schemes can thus be developed. A review of these pharmacodynamic and pharmacokinetic principles that will allow clinicians to administer drugs to provide a more optimal anesthetic is provided.

Intraosseous injection as an adjunct to conventional local anesthetic techniques: A clinical study.

PubMed

Idris, Mohamed; Sakkir, Nasil; Naik, Kishore Gopalakrishna; Jayaram, Nandakishore Kunijal

2014-09-01

The achievement of successful local anesthesia is a continual challenge in dentistry. Adjunctive local anesthetic techniques and their armamentaria, such as intraosseous injection (the Stabident system and the X-tip system) have been proposed to be advantageous in cases where the conventional local anesthetic techniques have failed. A clinical study was undertaken using intraosseous injection system by name X-tip to evaluate its effectiveness in cases where inferior alveolar nerve block has failed to provide pulpal anesthesia. Sixty adult patients selected were to undergo endodontic treatment for a mandibular molar tooth. Inferior alveolar nerve block was given using 4% articaine with 1:100,000 epinephrine. Twenty-four patients (40%) had pain even after administration of IAN block; intraosseous injection was administered using 4% articaine containing 1:100,000 epinephrine, using the X-tip system. The success of X-tip intraosseous injection was defined as none or mild pain (Heft-Parker visual analog scale ratings ≤ 54 mm) on endodontic access or initial instrumentation. Intraosseous injection technique was successful in 21 out of 24 patients (87.5%), except three patients who had pain even after supplemental X-tip injection. Within the limits of this study, we can conclude that supplemental intraosseous injection using 4% articaine with 1:100,000 epinephrine has a statistically significant influence in achieving pulpal anesthesia in patients with irreversible pulpitis.

Local anesthetic-induced myotoxicity as a cause of severe trismus after inferior alveolar nerve block.

PubMed

Smolka, Wenko; Knoesel, Thomas; Mueller-Lisse, Ullrich

2018-01-01

A case of a 60-year-old man with severe trismus after inferior alveolar nerve block is presented. MRI scans as well as histologic examination revealed muscle fibrosis and degeneration of the medial part of the left temporal muscle due to myotoxicity of a local anesthetic agent.

Anesthetic diffusion through lipid membranes depends on the protonation rate.

PubMed

Pérez-Isidoro, Rosendo; Sierra-Valdez, F J; Ruiz-Suárez, J C

2014-12-18

Hundreds of substances possess anesthetic action. However, despite decades of research and tests, a golden rule is required to reconcile the diverse hypothesis behind anesthesia. What makes an anesthetic to be local or general in the first place? The specific targets on proteins, the solubility in lipids, the diffusivity, potency, action time? Here we show that there could be a new player equally or even more important to disentangle the riddle: the protonation rate. Indeed, such rate modulates the diffusion speed of anesthetics into lipid membranes; low protonation rates enhance the diffusion for local anesthetics while high ones reduce it. We show also that there is a pH and membrane phase dependence on the local anesthetic diffusion across multiple lipid bilayers. Based on our findings we incorporate a new clue that may advance our understanding of the anesthetic phenomenon.

Anesthetic Diffusion Through Lipid Membranes Depends on the Protonation Rate

PubMed Central

Pérez-Isidoro, Rosendo; Sierra-Valdez, F. J.; Ruiz-Suárez, J. C.

2014-01-01

Hundreds of substances possess anesthetic action. However, despite decades of research and tests, a golden rule is required to reconcile the diverse hypothesis behind anesthesia. What makes an anesthetic to be local or general in the first place? The specific targets on proteins, the solubility in lipids, the diffusivity, potency, action time? Here we show that there could be a new player equally or even more important to disentangle the riddle: the protonation rate. Indeed, such rate modulates the diffusion speed of anesthetics into lipid membranes; low protonation rates enhance the diffusion for local anesthetics while high ones reduce it. We show also that there is a pH and membrane phase dependence on the local anesthetic diffusion across multiple lipid bilayers. Based on our findings we incorporate a new clue that may advance our understanding of the anesthetic phenomenon. PMID:25520016

The nicotinic acetylcholine receptor: Binding of nitroxide analogs of a local anesthetic and a photoactivatable analog of phosphatidylserine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blanton, M.P.

1989-01-01

Electron spin resonance was used to contrast the accessibility of tertiary and quaternary amine local anesthetics to their high affinity binding site in the desensitized Torpedo californica acetylcholine receptor (AchR). Preincubation of AchR-rich membranes with agonist resulted in a substantial reduction in the initial association of the quaternary amine local anesthetic C6SLMEI with the receptor. The time-dependent reduction in association follows a biphasic exponential function having rate constants of 0.19 min{sup {minus}1} and 0.03 min{sup {minus}1}. In contrast, agonist preincubation did not produce a comparable decrease in the association of C6SL, a tertiary amine analog, with the AchR. The resultsmore » are modeled in two ways: (1) A charge gate near the channel mouth in the desensitized receptor limits access of the permanently charged cationic local anesthetic (C6SLMEI), but not for the uncharged form of the tertiary amine anesthetic C6SL. (2) A hydrophobic pathway, possibly through a corridor in the annular lipid surrounding receptor subunits, allows the uncharged form of C6SL to reach the high affinity binding site in the AchR. A photoactivatable analog of phosphatidylserine {sup 125}I 4-azido salicylic acid-phosphatidylserine ({sup 125}I ASA-PS) was use to label both Torpedo californica acetylcholine receptor-rich membranes and reconstituted AchR membranes. All four subunits of the AchR were found to incorporate label, with the {alpha} subunit incorporating approximately twice as much as each of the other subunits on a per mole basis. The regions of the AchR {alpha} subunit that incorporate {sup 125}I ASA-PS were mapped by Staphylococcus aureus V8 protease digestion. Eighty-one per cent of the incorporated label was localized to 11.7 and 10.1 kdal V8 cleavage fragments.« less

Titration calorimetry of anesthetic-protein interaction: negative enthalpy of binding and anesthetic potency.

PubMed Central

Ueda, I; Yamanaka, M

1997-01-01

Anesthetic potency increases at lower temperatures. In contrast, the transfer enthalpy of volatile anesthetics from water to macromolecules is usually positive. The transfer decreases at lower temperature. It was proposed that a few selective proteins bind volatile anesthetics with negative delta H, and these proteins are involved in signal transduction. There has been no report on direct estimation of binding delta H of anesthetics to proteins. This study used isothermal titration calorimetry to analyze chloroform binding to bovine serum albumin. The calorimetrically measured delta H cal was -10.37 kJ.mol-1. Thus the negative delta H of anesthetic binding is not limited to signal transduction proteins. The binding was saturable following Fermi-Dirac statistics and is characterized by the Langmuir adsorption isotherms, which is interfacial. The high-affinity association constant, K, was 2150 +/- 132 M-1 (KD = 0.47 mM) with the maximum binding number, Bmax = 3.7 +/- 0.2. The low-affinity K was 189 +/- 3.8 M-1 (KD = 5.29 mM), with a Bmax of 13.2 +/- 0.3. Anesthetic potency is a function of the activity of anesthetic molecules, not the concentration. Because the sign of delta H determines the temperature dependence of distribution of anesthetic molecules, it is irrelevant to the temperature dependence of anesthetic potency. PMID:9083685

The successful use of intralipid for treatment of local anesthetic-induced central nervous system toxicity: Some considerations for administration of intralipid in an emergency.

PubMed

Espinet, Anthony J; Emmerton, Mark T

2009-01-01

Intralipid has been proposed as a treatment option for local anesthetic (LA) toxicity, which does not respond to traditional resuscitation methods. This paper presents a case report of a patient who developed signs of local anesthetic toxicity and was subsequently treated with 20% Intralipid with a positive response. Some background and practical applications regarding this treatment are discussed.

Lidocaine Concentration in Oral Tissue by the Addition of Epinephrine

PubMed Central

Tanaka, Eri; Yoshida, Kenji; Kawaai, Hiroyoshi; Yamazaki, Shinya

2016-01-01

The vasoconstrictive effect due to the addition of epinephrine to local anesthetic has been clearly shown by measuring blood-flow volume or blood anesthetic concentration in oral mucosal tissue. However, there are no reports on the measurement of anesthetic concentration using samples directly taken from the jawbone and oral mucosal tissue. Consequently, in this study, the effect of lidocaine concentration in the jawbone and oral mucosal tissue by the addition of epinephrine to the local anesthetic lidocaine was considered by quantitatively measuring lidocaine concentration within the tissue. Japanese white male rabbits (n = 96) were used as test animals. General anesthesia was induced by sevoflurane and oxygen, and then cannulation to the femoral artery was performed while arterial pressure was constantly recorded. Infiltration anesthesia was achieved by 0.5 mL of 2% lidocaine containing 1 : 80,000 epinephrine in the upper jawbone (E+) and 0.5 mL of 2% of epinephrine additive–free lidocaine (E0) under the periosteum. At specified time increments (10, 20, 30, 40, 50, and 60 minutes), samples from the jawbone, oral mucosa, and blood were collected, and lidocaine concentration was directly measured by high-performance liquid chromatography. No significant differences in the change in blood pressure were observed either in E+ or E0. In both E+ and E0 groups, the serum lidocaine concentration peaked 10 minutes after local anesthesia and decreased thereafter. At all time increments, serum lidocaine concentration in E+ was significantly lower than that in E0. There were no significant differences in measured lidocaine concentration between jawbone and mucosa within either the E+ or the E0 groups at all time points, although the E0 group had significantly lower jawbone and mucosa concentrations than the E+ group at all time points when comparing the 2 groups to each other. Addition of epinephrine to the local anesthetic inhibited systemic absorption of local

Lidocaine Concentration in Oral Tissue by the Addition of Epinephrine.

PubMed

Tanaka, Eri; Yoshida, Kenji; Kawaai, Hiroyoshi; Yamazaki, Shinya

2016-01-01

The vasoconstrictive effect due to the addition of epinephrine to local anesthetic has been clearly shown by measuring blood-flow volume or blood anesthetic concentration in oral mucosal tissue. However, there are no reports on the measurement of anesthetic concentration using samples directly taken from the jawbone and oral mucosal tissue. Consequently, in this study, the effect of lidocaine concentration in the jawbone and oral mucosal tissue by the addition of epinephrine to the local anesthetic lidocaine was considered by quantitatively measuring lidocaine concentration within the tissue. Japanese white male rabbits (n = 96) were used as test animals. General anesthesia was induced by sevoflurane and oxygen, and then cannulation to the femoral artery was performed while arterial pressure was constantly recorded. Infiltration anesthesia was achieved by 0.5 mL of 2% lidocaine containing 1 : 80,000 epinephrine in the upper jawbone (E(+)) and 0.5 mL of 2% of epinephrine additive-free lidocaine (E(0)) under the periosteum. At specified time increments (10, 20, 30, 40, 50, and 60 minutes), samples from the jawbone, oral mucosa, and blood were collected, and lidocaine concentration was directly measured by high-performance liquid chromatography. No significant differences in the change in blood pressure were observed either in E(+) or E(0). In both E(+) and E(0) groups, the serum lidocaine concentration peaked 10 minutes after local anesthesia and decreased thereafter. At all time increments, serum lidocaine concentration in E(+) was significantly lower than that in E(0). There were no significant differences in measured lidocaine concentration between jawbone and mucosa within either the E(+) or the E(0) groups at all time points, although the E(0) group had significantly lower jawbone and mucosa concentrations than the E(+) group at all time points when comparing the 2 groups to each other. Addition of epinephrine to the local anesthetic inhibited systemic

Occupational Exposure of Veterinarians to Waste Anesthetic Gases

DTIC Science & Technology

1987-05-07

The two most frequently used anesthetic gases, methoxyflurane and halothane. were chosen to be studied.) Exposures during 38 surgeries were /"studied...use of anesthetic agent for small animals. The halothane concentrations were higher than the methoxyflurane concentrations because of the out of - ,&t...exposures by 2.7 fold for methoxyflurane and 43 fold for halothane. However, during back to back surgeries a gradual build-up of anesthetic gas was found

Intramuscular Local Anesthetic Infiltration at Closure for Postoperative Analgesia in Lumbar Spine Surgery: A Systematic Review and Meta-Analysis.

PubMed

Perera, Andrea P; Chari, Aswin; Kostusiak, Milosz; Khan, Akbar Ali; Luoma, Astri Mv; Casey, Adrian T H

2017-07-15

Systematic Review and Meta-Analysis OBJECTIVE.: To identify whether intramuscular local anesthetic infiltration prior to wound closure was effective in reducing postoperative pain and facilitating early discharge following lumbar spine surgery. Local anesthetic infiltration prior to wound closure may form part of the multimodal strategy for postoperative analgesia, facilitating early mobilization and discharge. Although there are a number of small studies investigating its utility, a quantitative meta-analysis of the data has never been performed. This review was conducted according the PRISMA statement and was registered with the PROSPERO database. Only randomized controlled trials were eligible for inclusion. Key outcomes of interest included time to first analgesic demand, total postoperative opiate usage in the first 24 hours, visual analogue score (VAS) at 1, 12 and 24 hours and postoperative length of stay. Eleven publications fulfilled the inclusion criteria. A total of 438 patients were include; 212 in the control group and 226 in the intervention group. Local anesthetic infiltration resulted in a prolonged time to first analgesic demand (mean difference (MD) 65.88 minutes, 95% confidence interval (95% CI) 23.70 to 108.06, P.0.002) as well as a significantly reduced postoperative opiate demand (M.D. -9.71 mg, 95% CI -15.07, -4.34, p = 0.0004). There was a small but statistically significant reduction in postoperative visual analogue score (VAS) at 1 hour (M.D. -0.87 95%CI -1.55, -0.20, p = 0.01), but no significant reduction at 12 or 24 hours (p = 0.93 and 0.85 respectively). This systematic review and meta-analysis provides evidence that postoperative intramuscular local anaesthetic infiltration reduces postoperative analgesic requirements and the time to first analgesic demands for patients undergoing lumbar spine surgery. Key research priorities include optimization of the choice and strength of local anaesthetic agent and health

Intraosseous injection as an adjunct to conventional local anesthetic techniques: A clinical study

PubMed Central

Idris, Mohamed; Sakkir, Nasil; Naik, Kishore Gopalakrishna; Jayaram, Nandakishore Kunijal

2014-01-01

Background: The achievement of successful local anesthesia is a continual challenge in dentistry. Adjunctive local anesthetic techniques and their armamentaria, such as intraosseous injection (the Stabident system and the X-tip system) have been proposed to be advantageous in cases where the conventional local anesthetic techniques have failed. Aim: A clinical study was undertaken using intraosseous injection system by name X-tip to evaluate its effectiveness in cases where inferior alveolar nerve block has failed to provide pulpal anesthesia. Materials and Methods: Sixty adult patients selected were to undergo endodontic treatment for a mandibular molar tooth. Inferior alveolar nerve block was given using 4% articaine with 1:100,000 epinephrine. Twenty-four patients (40%) had pain even after administration of IAN block; intraosseous injection was administered using 4% articaine containing 1:100,000 epinephrine, using the X-tip system. The success of X-tip intraosseous injection was defined as none or mild pain (Heft-Parker visual analog scale ratings ≤ 54 mm) on endodontic access or initial instrumentation. Results: Intraosseous injection technique was successful in 21 out of 24 patients (87.5%), except three patients who had pain even after supplemental X-tip injection. Conclusion: Within the limits of this study, we can conclude that supplemental intraosseous injection using 4% articaine with 1:100,000 epinephrine has a statistically significant influence in achieving pulpal anesthesia in patients with irreversible pulpitis. PMID:25298642

(/sup 3/H)Batrachotoxinin A 20 alpha-benzoate binding to voltage-sensitive sodium channels: a rapid and quantitative assay for local anesthetic activity in a variety of drugs

DOE Office of Scientific and Technical Information (OSTI.GOV)

McNeal, E.T.; Lewandowski, G.A.; Daly, J.W.

1985-03-01

(/sup 3/H)Batrachotoxinin A benzoate ((/sup 3/H)BTX-B) binds with high affinity to sites on voltage-dependent sodium channels in a vesicular preparation from guinea pig cerebral cortex. In this preparation, local anesthetics competitively antagonize the binding of (/sup 3/H)BTX-B. The potencies of some 40 classical local anesthetics and a variety of catecholamine, histamine, serotonin, adenosine, GABA, glycine, acetylcholine, and calcium antagonists, tranquilizers, antidepressants, barbiturates, anticonvulsants, steroids, vasodilators, antiinflammatories, anticoagulants, analgesics, and other agents have been determined. An excellent correlation with the known local anesthetic activity of many of these agents indicate that antagonism of binding of (/sup 3/H)BTX-B binding provides a rapid,more » quantitative, and facile method for the screening and investigation of local anesthetic activity.« less

Interactions of the local anesthetic tetracaine with membranes containing phosphatidylcholine and cholesterol: a /sup 2/H NMR study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Auger, M.; Jarrell, H.C.; Smith, I.C.P.

1988-06-28

The interactions of local anesthetic tetracaine with multilamellar dispersions of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and cholesterol have been investigated by deuterium nuclear magnetic resonance of specifically deuteriated tetracaines, DMPC and cholesterol. Experiments were performed at pH 5.5, when the anesthetic is primarily charged, and at pH 9.5, when it is primarily uncharged. The partition coefficients of the anesthetic in the membrane have been measured at both pH values for phosphatidylcholine bilayers with and without cholesterol. The higher partition coefficients obtained at pH 9.5 reflect the hydrophobic interactions between the uncharged form of the anesthetic and the hydrocarbon region of the bilayer. Themore » lower partition coefficients for the DMPC/cholesterol system at both pH values suggest that cholesterol, which increases the order of the lipid chains, decreases the solubility of tetracaine into the bilayer. For phosphatidylcholine bilayers, it has been proposed that the charged tetracaine at low pH is located mostly at the phospholipid headgroup level while the uncharged tetracaine intercalates more deeply into the bilayer. The present study suggests that the location of tetracaine in the cholesterol-containing system is different from that in pure phosphatidylcholine bilayers: the anesthetic sits higher in the membrane. An increase in temperature results in a deeper penetration of the anesthetic into the bilayer. Moreover, the incorporation of the anesthetic into DMPC bilayers with or without cholesterol results in a reduction of the lipid order parameters both in the plateau and in the tail regions of the acyl chains, this effect being greater with the charged form of the anesthetic.« less

Benzocaine loaded solid lipid nanoparticles: Formulation design, in vitro and in vivo evaluation of local anesthetic effect.

PubMed

Basha, Mona; Abd El-Alim, Sameh Hosam; Kassem, Ahmed Alaa; El Awdan, Sally; Awad, Gamal

2015-01-01

The aim of the present work is the development and evaluation of solid lipid nanoparticles (SLNs) as carrier system for topical delivery of benzocaine (BZC) improving its local anesthesia aiming to produce a fast acting and long lasting topical formulation. BZC loaded SLNs were prepared using a full factorial design to study the influence of the type of polyoxyethylene sorbitan ester surfactants as well as their concentration as independent variables on the particle size, entrapment efficacy and zeta potential selected as dependent variables. Design of experiment (DOE) and the analysis of variance (ANOVA) were conducted to assess the optimization of the developed formulations. The results indicated that the fatty acid chain length of tested surfactants and their concentration had a significant effect on the studied responses. The optimized formulations were spherical in shape of mean particle diameters<350 nm with negatively charged surface <-20mV. Particles were characterized using differential scanning calorimetry and X-ray powder diffraction confirming the amorphous nature and the uniformity of drug inclusion in the lipid matrix. Optimized BZC-SLNs were incorporated into hydrogels characterized by a pseudoplastic non-Newtonian behavior. In vitro release study revealed an apparently biphasic release process with sustained release profile following Higuchi kinetics. BZC loaded SLNs hydrogels showed more potent anesthetic effect compared to BZC hydrogel evaluated using tail-flick analgesimeter, confirming significant improvement in both the intensity and duration of anesthetic effect. The above results proved that SLNs represent good candidates to encapsulate BZC improving its therapeutic efficacy for the topical treatment of pain.

Calculation of the transitions in the amine inversion vibration of some local anesthetics

NASA Astrophysics Data System (ADS)

Alcolea Palafox, M.

1988-05-01

In the para-amino group of the local anesthetics benzocaine, procaine and procaine hydrochloride, the potential function of inversion, the barrier height V̂ i and the optimum ω o inversion angle have been determinated. Two methods are shown for calculating transitions based on the two frequencies of inversion which easily can be detected in the infrared absorption and Raman spectra in solid compounds. Also the frequencies associated with tra nsitions are able to be obtained.

The Third American Society of Regional Anesthesia and Pain Medicine Practice Advisory on Local Anesthetic Systemic Toxicity: Executive Summary 2017.

PubMed

Neal, Joseph M; Barrington, Michael J; Fettiplace, Michael R; Gitman, Marina; Memtsoudis, Stavros G; Mörwald, Eva E; Rubin, Daniel S; Weinberg, Guy

2018-02-01

The American Society of Regional Anesthesia and Pain Medicine's Third Practice Advisory on local anesthetic systemic toxicity is an interim update from its 2010 advisory. The advisory focuses on new information regarding the mechanisms of lipid resuscitation, updated frequency estimates, the preventative role of ultrasound guidance, changes to case presentation patterns, and limited information related to local infiltration anesthesia and liposomal bupivacaine. In addition to emerging information, the advisory updates recommendations pertaining to prevention, recognition, and treatment of local anesthetic systemic toxicity. WHAT'S NEW IN THIS UPDATE?: This interim update summarizes recent scientific findings that have enhanced our understanding of the mechanisms that lead to lipid emulsion reversal of LAST, including rapid partitioning, direct inotropy, and post-conditioning. Since the previous practice advisory, epidemiological data have emerged that suggest a lower frequency of LAST as reported by single institutions and some registries, nevertheless a considerable number of events still occur within the general community. Contemporary case reports suggest a trend toward delayed presentation, which may mirror the increased use of ultrasound guidance (fewer intravascular injections), local infiltration techniques (slower systemic uptake), and continuous local anesthetic infusions. Small patient size and sarcopenia are additional factors that increase potential risk for LAST. An increasing number of reported events occur outside of the traditional hospital setting and involve non-anesthesiologists.

Inhibition of spinal protein kinase C-epsilon or -gamma isozymes does not affect halothane minimum alveolar anesthetic concentration in rats.

PubMed

Shumilla, Jennifer A; Sweitzer, Sarah M; Eger, Edmond I; Laster, Michael J; Kendig, Joan J

2004-07-01

Anesthetic effects on receptor or ion channel phosphorylation by enzymes such as protein kinase C (PKC) have been postulated to underlie some aspects of anesthesia. In vitro studies show that anesthetic effects on several receptors are mediated by PKC. To test the importance of PKC for the immobility produced by inhaled anesthetics, we measured the effect of intrathecal injections of PKC-epsilon and -gamma inhibitors on halothane minimum alveolar anesthetic concentration (MAC) in 7-day-old and 21-day-old Sprague-Dawley rats. The inhibitors were made as solutions of 100 pmol/5 microL and were given in a volume of 5 microL (7-day-old [P7] rats) or 10 microL (21-day-old [P21] rats). Controls were saline injections or injections of the peptide carrier at the same concentration and volumes; there were six animals in each group. In P7 rats, MAC values (in percentage of an atmosphere) were 1.63 +/- 0.0727 (mean +/- SEM) in saline controls, 1.55 +/- 0.141 in carrier controls, 1.54 +/- 0.0800 in rats given PKC-epsilon, and 1.69 +/- 0.0554 in rats given PKC-gamma. In P21 animals, the values were 1.20 +/- 0.0490, 1.31 +/- 0.0124, 1.27 +/- 0.0367, and 1.15 +/- 0.0483, respectively. Injection of the inhibitors did not change MAC in either age group. These results do not support an anesthetic effect on phosphorylation as a mechanism underlying the capacity of inhaled anesthetics to prevent movement in response to noxious stimulation, and they indirectly support a direct action on receptors or ion channels.

Host-guest complexes of local anesthetics with cucurbit[6]uril and para-sulphonatocalix[8]arene in the solid state

NASA Astrophysics Data System (ADS)

Danylyuk, Oksana; Butkiewicz, Helena; Coleman, Anthony W.; Suwinska, Kinga

2017-12-01

Here we describe the host-guest inclusion complexes of local anesthetic drugs with two macrocyclic hosts cucurbit[6]uril and para-sulphonatocalix[8]arene in the solid state. The anesthetic agents used in the co-crystallization with the supramolecular hosts are lidocaine, procaine, procainamide, prilocaine and proparacaine. Both macrocycles encapsulate the alkylammonium moieties of anestetics guests into their cavities although the mechanism of complexation, host-guest stoichiometry and geometry differ depending on the nature of the supramolecular host.

Anesthetic cartridge system under evaluation.

PubMed

Cooley, R L; Lubow, R M

1981-01-01

The problem of glass breakage in the local anesthetic cartridge system was evaluated under laboratory conditions with a mechanical testing machine. The anticipated breakage of the glass did not occur with any frequency, as the rubber stopper produced more uniform failures of the system. The glass cartridge appeared to be quite reliable and resistant to breakage.Local anesthetics have been used for many years to provide patients temporary freedom from pain. Local anesthetic solutions are in wide use in both dentistry and medicine and are the most frequently used drugs in dentistry. Various estimates place the number of injections at approximately one half million daily or 125 million injections per year.These drugs and the armamentarium necessary to administer them have proven to be safe and reliable. Only rarely are there reports of sensitivity to the anesthetic solution or breakage of needles.. Sterility of the solutions has not been a problem as they are carefully processed and evaluated at the factory. Although there are sporadic reports of loss of sterility, this has been attributed to the reuse of the anesthetic cartridges on more than one patient. Monheim states "The success of the cartridge system in dentistry has been due to the sincerity, honesty, and high standards of the manufacturers in giving the profession a near-perfect product." However, on occassion a glass cartridge will break or shatter when inserting the harpoon into the rubber stopper or even during injection. Cooley et al reported on eye injuries occurring in the dental office, one of which was due to glass from a local anesthetic cartridge that exploded and propelled particles into the patient's eye. Forrest evaluated syringes, needles, and cartridges and reported that one brand (made in Britain) fractured more often than any other, but that the fracture rate was too low to be of any consequence.It is apparent that glass cartridges will fracture or burst from time to time. This study

Anesthetic Cartridge System Under Evaluation

PubMed Central

Cooley, Robert L.; Lubow, Richard M.

1981-01-01

The problem of glass breakage in the local anesthetic cartridge system was evaluated under laboratory conditions with a mechanical testing machine. The anticipated breakage of the glass did not occur with any frequency, as the rubber stopper produced more uniform failures of the system. The glass cartridge appeared to be quite reliable and resistant to breakage. Local anesthetics have been used for many years to provide patients temporary freedom from pain. Local anesthetic solutions are in wide use in both dentistry and medicine and are the most frequently used drugs in dentistry. Various estimates place the number of injections at approximately one half million daily or 125 million injections per year. These drugs and the armamentarium necessary to administer them have proven to be safe and reliable. Only rarely are there reports of sensitivity to the anesthetic solution or breakage of needles.. Sterility of the solutions has not been a problem as they are carefully processed and evaluated at the factory. Although there are sporadic reports of loss of sterility, this has been attributed to the reuse of the anesthetic cartridges on more than one patient. Monheim states “The success of the cartridge system in dentistry has been due to the sincerity, honesty, and high standards of the manufacturers in giving the profession a near-perfect product.” However, on occassion a glass cartridge will break or shatter when inserting the harpoon into the rubber stopper or even during injection. Cooley et al reported on eye injuries occurring in the dental office, one of which was due to glass from a local anesthetic cartridge that exploded and propelled particles into the patient's eye. Forrest evaluated syringes, needles, and cartridges and reported that one brand (made in Britain) fractured more often than any other, but that the fracture rate was too low to be of any consequence. It is apparent that glass cartridges will fracture or burst from time to time. This study

Effects of ventilation on hyaluronan and protein concentration in pleural liquid of anesthetized and conscious rabbits.

PubMed

Wang, P M; Lai-Fook, S J

1998-01-01

The hypothesis of this study is that pleural lubrication is enhanced by hyaluronan acting as a boundary lubricant in pleural liquid and by pleural filtration as reflected in changes in protein concentration with ventilation. Anesthetized rabbits were injected intravenously with Evans blue dye and ventilated with 100% O2 at either of two levels of ventilation for 6 h. Postmortem values of hyaluronan, total protein, and Evans blue-dyed albumin (EBA) concentrations in pleural liquid were greater at the higher ventilation, consistent with increases in boundary lubrication, pleural membrane permeability, and pleural filtration. To determine whether these effects were caused by hyperoxia or anesthesia, conscious rabbits were ventilated with either 3% CO2 or room air in a box for 6, 12, or 24 h. Similar to the anesthetized rabbits, pleural liquid hyaluronan concentration after 24 h was higher in the conscious rabbits with the hypercapnic-induced greater ventilation. By contrast, the time course of total protein and EBA in pleural liquid was similar in both groups of conscious rabbits, indicating no effect of ventilation on pleural permeability. The increase in pleural liquid hyaluronan concentration might be the result of mesothelial cell stimulation by a ventilation-induced increase in pleural liquid shear stress.

Advanced technologies and devices for inhalational anesthetic drug dosing.

PubMed

Meyer, J-U; Kullik, G; Wruck, N; Kück, K; Manigel, J

2008-01-01

Technological advances in micromechanics, optical sensing, and computing have led to innovative and reliable concepts of precise dosing and sensing of modern volatile anesthetics. Mixing of saturated desflurane flow with fresh gas flow (FGF) requires differential pressure sensing between the two circuits for precise delivery. The medical gas xenon is administered most economically in a closed circuit breathing system. Sensing of xenon in the breathing system is achieved with miniaturized and unique gas detector systems. Innovative sensing principles such as thermal conductivity and sound velocity are applied. The combination of direct injection of volatile anesthetics and low-flow in a closed circuit system requires simultaneous sensing of the inhaled and exhaled gas concentrations. When anesthetic conserving devices are used for sedation with volatile anesthetics, regular gas concentration monitoring is advised. High minimal alveolar concentration (MAC) of some anesthetics and low-flow conditions bear the risk of hypoxic gas delivery. Oxygen sensing based on paramagnetic thermal transduction has become the choice when long lifetime and one-time calibration are required. Compact design of beam splitters, infrared filters, and detectors have led to multiple spectra detector systems that fit in thimble-sized housings. Response times of less than 500 ms allow systems to distinguish inhaled from exhaled gas concentrations. The compact gas detector systems are a prerequisite to provide "quantitative anesthesia" in closed circuit feedback-controlled breathing systems. Advanced anesthesia devices in closed circuit mode employ multiple feedback systems. Multiple feedbacks include controls of volume, concentrations of anesthetics, and concentration of oxygen with a corresponding safety system. In the ideal case, the feedback system delivers precisely what the patient is consuming. In this chapter, we introduce advanced technologies and device concepts for delivering

Solubility of Haloether Anesthetics in Human and Animal Blood

PubMed Central

Soares, Joao H. N.; Brosnan, Robert J.; Fukushima, Fabíola B.; Hodges, Joanne; Liu, Hong

2012-01-01

Background Anesthetic blood solubility predicts pharmacokinetics for inhaled agents and is essential for determination of blood anesthetic concentrations from end-tidal gas concentrations using Henry’s Law. Though used to model anesthetic effects in humans, there are limited interspecies solubility comparisons that include modern haloethers. This study aimed to measure hematocrit-adjusted blood:gas anesthetic partition coefficients (λB:G) for desflurane, sevoflurane, isoflurane, and methoxyflurane in humans and animals. Methods Whole blood was collected from 20 rats, 8 horses, and 4 each of cats, cattle, humans, dogs, goats, pigs, rabbits, and sheep. Plasma or cell volume was removed to adjust all samples to a packed cell volume of 40%. A single agent calibration gas headspace was added to blood in a glass syringe and was mixed and equilibrated at 37°C for 2 hours. Agent concentrations in the calibration gas and syringe headspace were measured using gas chromatography. Anesthetic solubility in saline, citrate-phosphate-dextrose-adenine, and olive oil were similarly measured. Results Except for goats, all animal species had at least one λB:G measurement that differed significantly from humans. For each agent, λB:G positively correlated with serum triglyceride concentrations, but this only explained 25% of interspecies variability. Desflurane was significantly less soluble in blood than sevoflurane in some species (e.g., humans) but not in others (e.g., rabbits). Conclusions Anesthetic partition coefficients differ significantly between humans and most animals for haloether anesthetics. Because of their similar λB:G values, goats may be a better animal model for inhaled anesthetic pharmacokinetics in people. PMID:22510863

Solubility of haloether anesthetics in human and animal blood.

PubMed

Soares, Joao H N; Brosnan, Robert J; Fukushima, Fabíola B; Hodges, Joanne; Liu, Hong

2012-07-01

Anesthetic blood solubility predicts pharmacokinetics for inhaled agents and is essential for determination of blood anesthetic concentrations from end-tidal gas concentrations using Henry's Law. Though used to model anesthetic effects in humans, there are limited interspecies solubility comparisons that include modern haloethers. This study aimed to measure hematocrit-adjusted blood:gas anesthetic partition coefficients (λ B:G) for desflurane, sevoflurane, isoflurane, and methoxyflurane in humans and animals. Whole blood was collected from 20 rats, 8 horses, and 4 each of cats, cattle, humans, dogs, goats, pigs, rabbits, and sheep. Plasma or cell volume was removed to adjust all samples to a packed cell volume of 40%. A single-agent calibration gas headspace was added to blood in a glass syringe and was mixed and equilibrated at 37°C for 2 h. Agent concentrations in the calibration gas and syringe headspace were measured using gas chromatography. Anesthetic solubility in saline, citrate-phosphate-dextrose-adenine, and olive oil were similarly measured. Except for goats, all animal species had at least one λ B:G measurement that differed significantly from humans. For each agent, λ B:G positively correlated with serum triglyceride concentrations, but this only explained 25% of interspecies variability. Desflurane was significantly less soluble in blood than sevoflurane in some species (e.g., humans) but not in others (e.g., rabbits). Anesthetic partition coefficients differ significantly between humans and most animals for haloether anesthetics. Because of their similar λ B:G values, goats may be a better animal model for inhaled anesthetic pharmacokinetics in people.

Survey of Navy Dental Clinics: Materiel Complaints Regarding Carbide Burs and Local Anesthetics,

DTIC Science & Technology

1986-12-01

DECEMBER 1986 00w SURVEY OF NAVY DENTAL CLINICS: MATERIEL COMPLAINTS REGARDING CARBIDE BURS AND LOCAL ANESTHETICS J. R. KELLY M.T.HETZER aT TION SAThE14N...A A~Proved for Publc reeo.s.g C NAVAL 9-4 DENTAL RESEARCH INSTITUTE Naval Medical Research and Development Command Bethesda, Maryland -h 3 -1* q...NUMBER 2 GOVT ACCESSION NO. 3. RECIPIENT’S CATALOG NUMBER 4. TITLE (and Subtitle) S. TYPE OF REPORT & PERIOD COVERED SURVEY OF NAVY DENTAL CLINICS

Lipid emulsion improves survival in animal models of local anesthetic toxicity: a meta-analysis.

PubMed

Fettiplace, Michael R; McCabe, Daniel J

2017-08-01

The Lipid Emulsion Therapy workgroup, organized by the American Academy of Clinical Toxicology, recently conducted a systematic review, which subjectively evaluated lipid emulsion as a treatment for local anesthetic toxicity. We re-extracted data and conducted a meta-analysis of survival in animal models. We extracted survival data from 26 publications and conducted a random-effect meta-analysis based on odds ratio weighted by inverse variance. We assessed the benefit of lipid emulsion as an independent variable in resuscitative models (16 studies). We measured Cochran's Q for heterogeneity and I 2 to determine variance contributed by heterogeneity. Finally, we conducted a funnel plot analysis and Egger's test to assess for publication bias in studies. Lipid emulsion reduced the odds of death in resuscitative models (OR =0.24; 95%CI: 0.1-0.56, p = .0012). Heterogeneity analysis indicated a homogenous distribution. Funnel plot analysis did not indicate publication bias in experimental models. Meta-analysis of animal data supports the use of lipid emulsion (in combination with other resuscitative measures) for the treatment of local anesthetic toxicity, specifically from bupivacaine. Our conclusion differed from the original review. Analysis of outliers reinforced the need for good life support measures (securement of airway and chest compressions) along with prompt treatment with lipid.

Evolving Role of Local Anesthetics in Managing Postsurgical Analgesia.

PubMed

Golembiewski, Julie; Dasta, Joseph

2015-06-01

Opioid analgesics, the cornerstone of effective postsurgical pain management, may be associated with risk of opioid-related adverse drug events (ADEs) that may complicate the postsurgical experience. Perioperative multimodal analgesic regimens have the potential to improve postsurgical pain control and may permit use of lower analgesic doses and reduce the incidence of opioid-related ADEs. Utility of traditional local anesthetic formulations to provide analgesia over the entire postsurgical period is limited by their short duration of action. Liposome bupivacaine, a liposomal formulation of bupivacaine indicated for single-dose administration into the surgical site to produce postsurgical analgesia, was evaluated in multiple surgical models as part of multimodal analgesic regimens and was found in clinical trials to provide postsurgical analgesia for up to 72 hours. Here, we provide an overview of the available multimodal analgesic options and recent recommendations for optimal postsurgical pain management. A review of the literature was conducted, and results from recent clinical trials are included. The use of a multimodal analgesic regimen, including liposome bupivacaine, can extend the time to first postsurgical opioid use, may reduce postsurgical opioid consumption, and reduce hospital length of stay and costs compared with an opioid-only analgesic regimen. Use of multimodal analgesic regimens is a practical way to achieve good postsurgical analgesia while minimizing reliance on opioids and associated adverse events. Taken as a whole, evidence from the clinical studies of liposome bupivacaine suggests this local anesthetic formulation may be a useful component of multimodal analgesic regimens for managing postsurgical pain in select patients, with the potential to reduce opioid use and opioid-related ADEs in the postsurgical setting. As with bupivacaine, appropriate use of liposome bupivacaine to optimize clinical effects, economic implications, and patient

The effect of local anesthetic infiltration around nephrostomy tract on postoperative pain control after percutaneous nephrolithotomy.

PubMed

Tüzel, Emre; Kızıltepe, Günes; Akdoğan, Bülent

2014-08-01

The objective of the study was to investigate the effect of a long acting local anesthetic infiltration around nephrostomy tract on pain control after percutaneous nephrolithotomy. Forty-six patients with kidney stones of >2 cm undergoing single access subcostal percutaneous nephrolithotomy (PCNL) were enrolled in the study. Patients were randomized to levobupivacaine (Group I) and saline (Group II) infiltration groups. Group I patients (n = 23) had 75 mg/30 cc levobupivacaine infiltration around the access site after placement of nephrostomy catheter. Group II patients had 30 cc saline infiltration. Postoperatively the patients were given narcotics on demand. Pain scores were collected using a visual analog scale (VAS) at 2, 4, 6, 8, 12 and 24 h postoperatively. The VAS scores, time to analgesic demand, ambulation, and duration of nephrostomy tube were compared between two groups. The mean age was 44 and 45 years in group I and II patients. There were no significant differences between the two groups with regard to demographics, surgery or stone characteristics. Comparison of pain scores at all postoperative time points was not statistically significant between the two groups. Time to first analgesic demand and total narcotic analgesic dose per patient were 1.2 ± 1.05 and 4.04 ± 1.57 h; and 96 and 112 mg for group I and II patients (p = 0.009 and p = 0.41, respectively). Ambulation time and duration of nephrostomy tube were also similar. Infiltration of nephrostomy tract site with levobupivacaine does not have a superior effect compared to saline on postoperative pain control in patients undergoing PCNL.To prolong analgesia, the effect of intermittent tract injections or continuous infusion of local anesthetics for the postoperative maintenance of the local anesthetic effect seems worth to investigate in future studies.

Synthesis of Two Local Anesthetics from Toluene: An Organic Multistep Synthesis in a Project-Oriented Laboratory Course

ERIC Educational Resources Information Center

Demare, Patricia; Regla, Ignacio

2012-01-01

This article describes one of the projects in the advanced undergraduate organic chemistry laboratory course concerning the synthesis of two local anesthetic drugs, prilocaine and benzocaine, with a common three-step sequence starting from toluene. Students undertake, in a several-week independent project, the multistep synthesis of a…

Structural damage to periodontal tissues at varying rate of anesthetic injection.

PubMed

Sarapultseva, Maria; Sarapultsev, Alexey; Medvedeva, Svetlana; Danilova, Irina

2018-04-01

Incorrect administration of an anesthetic during local anesthesia is one of the most important causes of pain symptoms in patients scheduled for dental procedures. The current study assessed the severity of damage to periodontal tissue following different rates of anesthetic administration. The research was conducted on 50 outbred male rats with a body mass of 180-240 g. The anesthetic used was 1% articaine. The results showed that administration of the anesthetic at a rapid pace caused structural damage to the periodontal tissue. Further, signs of impaired microcirculation were noted at all rates of administration. Biochemical studies demonstrated changes in the level of glucose and enzymes with the rapid introduction of the anesthetic, indicating severe systemic stress response of the body. Injection of local anesthetic at any rate of introduction induces vascular congestion in the microcirculatory bloodstream and exudative reactions. Rapid introduction of an anesthetic causes progression of structural changes in the gingival tissue.

Ion transport processes in corn mitochondria : I. Effect of the local anesthetic dibucaine.

PubMed

Klein, R R; Koeppe, D E

1985-04-01

The local anesthetic dibucaine inhibited respiration-dependent contraction mediated by the K(+)/H(+) antiport system of isolated corn mitochondria. Respiration declined concurrently. Nigericin, an exogenous K(+)/H(+) exchanger, restored ion efflux in dibucaine-blocked corn mitochondria. It was concluded that dibucaine inhibited ion efflux via blockage of the K(+)/H(+) antiport. Further experiments determined that dibucaine also inhibited proton influx facilitated by protonophores and by the ATPase complex during state III respiration. These results are discussed in relation to the mechanism by which dibucaine inhibits proton translocation across the inner mitochondrial membrane.

The effect of local anesthetics administered via pain pump on chondrocyte viability.

PubMed

Dragoo, Jason L; Korotkova, Tatiana; Kanwar, Raj; Wood, Billy

2008-08-01

Chondrolysis initiated by postoperative, intra-articular pain pumps has recently been described by multiple institutions. To evaluate the in vitro chondrotoxicity of anesthetic formulations commonly used in pain pumps. Controlled laboratory study. Freshly isolated human articular chondrocytes were cultured for 24-, 48-, and 72-hour trials in a custom bioreactor that mimics the metabolism of synovial fluid. Chondrocytes were perfused in Dulbecco's Modified Eagle's Medium 10% fetal bovine serum and one of the following medications: 1% lidocaine, 1% lidocaine with epinephrine, 0.25% bupivacaine, 0.25% bupivacaine with epinephrine, 0.5% bupivacaine, or 0.5% bupivacaine with epinephrine. Static and perfusion cultures with growth media were used as controls. All experiments were run in duplicate. Live/dead staining was performed, and the ratio of dead:live cells was assessed by fluorescent microscopy and histomorphometry. Significantly more chondrocyte necrosis was found in all cultures with medications containing epinephrine (P < .05) at all time points. Similar necrosis rates were exhibited in 0.25% and 0.5% bupivacaine compared with controls at 24 and 48 hours. However, 0.5% bupivacaine produced significantly more cell death at 72 hours. Similar necrosis rates were exhibited with 1% lidocaine compared to controls at 24 hours. In this in vitro model, 0.25% and 0.5% bupivacaine caused minimal chondrocyte necrosis when used in pain pumps for a maximum of 48 hours. All anesthetics containing epinephrine (pH local anesthetics on chondrocyte viability.

Volatile anesthetics affect nutrient availability in yeast.

PubMed Central

Palmer, Laura K; Wolfe, Darren; Keeley, Jessica L; Keil, Ralph L

2002-01-01

Volatile anesthetics affect all cells and tissues tested, but their mechanisms and sites of action remain unknown. To gain insight into the cellular activities of anesthetics, we have isolated genes that, when overexpressed, render Saccharomyces cerevisiae resistant to the volatile anesthetic isoflurane. One of these genes, WAK3/TAT1, encodes a permease that transports amino acids including leucine and tryptophan, for which our wild-type strain is auxotrophic. This suggests that availability of amino acids may play a key role in anesthetic response. Multiple lines of evidence support this proposal: (i) Deletion or overexpression of permeases that transport leucine and/or tryptophan alters anesthetic response; (ii) prototrophic strains are anesthetic resistant; (iii) altered concentrations of leucine and tryptophan in the medium affect anesthetic response; and (iv) uptake of leucine and tryptophan is inhibited during anesthetic exposure. Not all amino acids are critical for this response since we find that overexpression of the lysine permease does not affect anesthetic sensitivity. These findings are consistent with models in which anesthetics have a physiologically important effect on availability of specific amino acids by altering function of their permeases. In addition, we show that there is a relationship between nutrient availability and ubiquitin metabolism in this response. PMID:12072454

Analgesic Effect of Botulinum Toxin A in Myofascial Pain Syndrome Patients Previously Treated with Local Infiltration of Anesthetic and Steroids.

PubMed

Cartagena-Sevilla, Joaquín; García-Fernández, María R; Vicente-Villena, Juan P

2016-12-01

The purpose of this study was to evaluate the analgesic effect of botulinum toxin A (BoNTA) injections in patients with myofascial pain syndrome (MPS) who were previously treated with the local infiltration of anesthetic and steroids (LIAS). The study included a retrospective phase and a longitudinal open-label prospective phase, which were conducted on consecutive patients with MPS previously treated with the local infiltration of anesthetic (levobupivacaíne 0.25%) and steroids (triamcinolone 40 mg). Eligible patients were treated with a single intramuscular injection of BoNTA (Botox; Allergan, Inc., Irvine, CA). The treatment efficacy was determined according to the degree of pain relief obtained. Eighty-two patients met the inclusion/exclusion criteria and were included in the study. Successful results were obtained for 32 (39.0%) and 30 (36.6%) patients, during treatment with BoNTA and LIAS, respectively. The mean (standard deviation) length of the analgesic effect was significantly longer with BoNTA (29.6 [SD = 17.7] weeks) than with LIAS (8.5 [SD = 6.4] weeks), P <.0001. As regards the side effects, 19 (23.2%) patients reported transient soreness at the injection site for 2 to 3 days with BoNTA. The MPS patients previously treated with a local infiltration of anesthetic and steroids who then received a single injection of BoNTA experienced significantly reduced pain for a relatively long time.

Cytotoxicity of solid lipid nanoparticles and nanostructured lipid carriers containing the local anesthetic dibucaine designed for topical application

NASA Astrophysics Data System (ADS)

Barbosa, R. M.; da Silva, C. M. G.; Bella, T. S.; de Araújo, D. R.; Marcato, P. D.; Durán, N.; de Paula, E.

2013-04-01

Dibucaine (DBC) is powerful long-lasting local anesthetic, but it is also considered fairly toxic to the CNS. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) have attracted attention as carriers for drug delivery. The aim of this study was to develop and to evaluate the cytotoxic activity of DBC-loaded SLN and NLC against 3T3 fibroblast and HaCat keratinocyte cells. The SLN and NLC had myristyl myristate and Liponate®GC as their lipid matrices, respectively, plus a surfactant. SLN and NLC were characterized in terms in their diameter, size distribution, surface charge and DBC encapsulation efficiency. The particle size of SLN and NLC were around 234.33 and 166.62 nm, respectively. The polydispersity index was kept below 0.2 for both nanomaterials. Negative surface charges were observed for both nanoparticles, which decreased in the presence of the anesthetic. Encapsulation efficiency reached 76% and 90%, respectively, in SLN and NLC. DBC alone was found to be toxic to 3T3 and HaCat cells in culture. However, NLC and SLN loaded DBC decreased its intrinsic cytotoxic effect against 3T3 and HaCat cells. In conclusion, encapsulation of DBC in SLN and NLC decreased the in vitro toxicity of the local anesthetic, indicating the potential of these nanocarriers for clinical applications.

Anesthetic effects from low concentrations of proparacaine and benoxinate.

PubMed

Jauregui, M J; Sanders, T J; Polse, K A

1980-01-01

Using double masking procedures, the response to McKay-Marg and Goldmann tonometry of 361 randomly selected patients was determined following the installation of a single dose of either 0.125, 0.25 or 0.5% proparacaine or 0.1, 0.2 or 0.4% benoxinate. Examiners graded the adequacy, patient tolerance and conjunctival hyperemia induced by the drop, while the subjects reported on the sting of the drop, awareness of the tonometer and discomfort after the procedure. The results indicate that 0.25% proparacaine is an effective anesthetic dose on all patients and that 0.2% benoxinate and 0.125% proparacaine would be effective on patients over age 40. The implication of these results is that significantly lower doses of anesthetic can be used which will result in less stinging, reduced hyperemia and shorter duration of action.

Use of anesthetics associated to vasoconstrictors for dentistry in patients with cardiopathies. Review of the literature published in the last decade.

PubMed

Serrera Figallo, María A; Velázquez Cayón, Rocío T; Torres Lagares, Daniel; Corcuera Flores, Jose R; Machuca Portillo, Guillermo

2012-04-01

The use of local anesthetics associated to vasoconstrictor agents in dentistry is thoroughly justified and is widely extended, but we cannot ignore the fact that anesthetic infiltration poses risk of complications throughout the dental treatment period. The objective of the present review is to document the reported effects the use of the local anesthetics most widely employed in dentistry, with or without association to vasoconstrictor agents may have in patients with any sort of cardiopathy. We have searched for randomized clinical trials on the assessment of the cardiovascular effects of local anesthetics used in dentistry, without limits as regards age or sex, conducted in patients with any type of cardiopathy which were published during the last decade and were index-linked in Cochrane, Embase and Medline. We have found six randomized clinical trials index-linked in Medline and Cochrane in the past ten years. These trials compare different types of anesthetics: lidocaine 2%, mepivacaine 2%, prilocaine 2% , associated or not to different vasoconstrictor concentrations such as adrenaline or felypressin. The cardiopathies affecting the patients included in the different trials range from hypertension, ischemic heart disease, arrythmias, chronic coronary disease to heart transplantation. The use of anesthetics associated to vasoconstrictor agents is justified in the case of patients with cardiopathies (once we get over the period in which any type of dental manipulation is contraindicated) and in controlled hypertensive patients. In any case, we must be very careful with the choice and execution of the anesthetic technique, being it possible to use a dose between 1.8 and 3.6 ml, on a general basis. Further studies are necessary to establish the effects of these drugs on severe hypertensive patients or in patients with other more advanced cardiopathies. Key words:Vasoconstrictor agents, epinephrine/adverse effects, local anesthetics, dental restoration, oral

Effect of dexmedetomidine injected into the oral mucosa in combination with lidocaine on local anesthetic potency in humans: a crossover double-blind study.

PubMed

Yamane, Ayaka; Higuchi, Hitoshi; Tomoyasu, Yumiko; Ishii-Maruhama, Minako; Maeda, Shigeru; Miyawaki, Takuya

2015-04-01

Recently, attention has been paid to dexmedetomidine, a selective α-2 adrenoceptor agonist, as a possible additive for local anesthesia. However, the effect of locally injected dexmedetomidine on the anesthetic action in humans has not fully been clarified. Thus, the purpose of the present study was to evaluate the effect of dexmedetomidine injected into the oral mucosa in combination with lidocaine on local anesthetic potency in humans. Twenty healthy volunteers were included in the present crossover double-blinded study. Lidocaine solution or lidocaine plus dexmedetomidine solution was submucosally injected into the alveolar mucosa in a crossover and double-blinded manner. The local anesthetic effect of the solutions was evaluated by measuring the current perception threshold (CPT) in the oral mucosa for 120 minutes after injection. Furthermore, the sedation level, blood pressure, and heart rate of the volunteers were evaluated. For statistical analysis, the Wilcoxon signed rank test and 2-way repeated measures analysis of variation were used. The CPT was increased with the 2 solutions and peaked 10 minutes after injection. CPT values 10 and 20 minutes after injection of lidocaine plus dexmedetomidine solution were considerably higher than those with lidocaine solution. The duration of an important increase in the CPT after injection with lidocaine plus dexmedetomidine solution was longer than that with lidocaine. Furthermore, the area under the time curve of CPT was considerably higher with lidocaine plus dexmedetomidine solution than with lidocaine solution. No volunteer showed a change in sedation level, blood pressure, or heart rate after injection with either test solution throughout the experiment. The present study showed that a combination of dexmedetomidine plus lidocaine considerably enhances the local anesthetic potency of lidocaine without any major influences on the cardiovascular system when locally injected into the oral mucosa. Copyright © 2015

Corneal anesthetic abuse and Candida keratitis.

PubMed

Chern, K C; Meisler, D M; Wilhelmus, K R; Jones, D B; Stern, G A; Lowder, C Y

1996-01-01

Topical corneal anesthetic abuse is a self-inflicted injury, causing profound corneal morbidity. Superimposed infection is an important complicating factor. The authors report four patients with confirmed topical anesthetic abuse of the cornea, in whom Candida keratitis developed. A retrospective review of the medical records of four patients with confirmed topical corneal anesthetic abuse and fungal keratitis. A 21-year-old woman, two 28-year-old women, and a 35-year-old man were included in the study. All these patients sustained a corneal injury, prompting the chronic use of topical anesthetics (0.5% proparacaine hydrochloride in 3 patients, and 0.5% tetracaine hydrochloride and 0.4% benoxinate hydrochloride in the other). Corneal findings included epithelial defects in all patients, focal infiltrate in one patient, and ring-shaped stromal infiltrate in three patients. Topical anesthetic was discontinued, all patients initially were treated empirically with antibacterial agents, and three patients received topical corticosteroids. Subsequent corneal cultures grew Candida spp, Candida albicans specifically in three patients, and local and systemic antifungal therapy was started. Corneas in two patients re-epithelialized; a conjunctival flap was performed on another patient with a descemetocele; and the remaining patient was lost to follow-up, although repeat fungal cultures yielded no growth. Corneal superinfection with Candida may occur during topical anesthetic abuse. Therapy includes discontinuation of the anesthetic and institution of antifungal therapy.

Anesthetic induction with guaifenesin and propofol in adult horses.

PubMed

Brosnan, Robert J; Steffey, Eugene P; Escobar, André; Palazoglu, Mine; Fiehn, Oliver

2011-12-01

To evaluate whether guaifenesin can prevent adverse anesthetic induction events caused by propofol and whether a guaifenesin-propofol induction combination has brief cardiovascular effects commensurate with rapid drug washout. 8 healthy adult horses. Guaifenesin was administered IV for 3 minutes followed by IV injection of a bolus of propofol (2 mg/kg). Additional propofol was administered if purposeful movement was detected. Anesthesia was maintained for 2 hours with isoflurane or sevoflurane at 1.2 times the minimum alveolar concentration with controlled normocapnic ventilation. Normotension was maintained via a dobutamine infusion. Plasma concentrations of propofol and guaifenesin were measured every 30 minutes. Mean ± SD guaifenesin and propofol doses inducing anesthesia in half of the horses were 73 ± 18 mg/kg and 2.2 ± 0.3 mg/kg, respectively. No adverse anesthetic induction events were observed. By 70 minutes, there was no significant temporal change in the dobutamine infusion rate required to maintain normotension for horses anesthetized with isoflurane or sevoflurane. Mean plasma guaifenesin concentrations were 122 ± 30 μM, 101 ± 33 μM, 93 ± 28 μM, and 80 ± 24 μM at 30, 60, 90, and 120 minutes after anesthetic induction, respectively. All plasma propofol concentrations were below the limit of quantitation. Guaifenesin prevented adverse anesthetic induction events caused by propofol. Guaifenesin (90 mg/kg) followed by propofol (3 mg/kg) should be sufficient to immobilize > 99% of calm healthy adult horses. Anesthetic drug washout was rapid, and there was no change in inotrope requirements after anesthesia for 70 minutes.

Continuous-infusion local anesthetic pain pump use and seroma formation with abdominal procedures: is there a correlation?

PubMed

Smith, Melissa M; Hovsepian, Raffi V; Markarian, Mark K; Degelia, Amber L; Paul, Malcolm D; Evans, Gregory R D; Wirth, Garrett A

2008-11-01

Seroma formation is the most commonly occurring complication in plastic surgery abdominal procedures. Continuous local anesthetic pain pump delivery systems are often used to decrease postoperative pain. An unreported concern with use of these devices in abdominal procedures is the effect of continuous fluid infiltration of the surgical site and a possible increase in the incidence of seroma formation. The authors performed a retrospective chart review to evaluate all patients (n = 159) who underwent abdominal procedures (abdominoplasty, panniculectomy, and transverse rectus abdominis myocutaneous flap harvest) over a 3-year period. Patient charts were evaluated for sex, age, body mass index, procedure performed, surgeon, operation length, pain pump use, postoperative seroma formation, and any complications. In cases with pain pump use, catheter placement location, anesthetic medication and strength, continuous-infusion rate, and duration of pain pump use were also reviewed. If a postoperative seroma formation was identified, treatment and outcomes were also recorded. The overall seroma formation rate was 11.3 percent (18 of 159 patients). Other complications occurred at a rate of 2.5 percent (four of 159). The incidence of seroma was 11.0 percent (11 of 100) in patients with pain pump use versus 11.9 percent (7 of 59) in those who did not use a pain pump. There was no statistically significant difference (p = 0.9) in the incidence of seroma formation between those who did and did not use a pain pump device. There was no correlation between increased rate of seroma formation and use of a continuous-infusion local anesthetic pain pump system in our patient population.

Benzocaine-loaded polymeric nanocapsules: study of the anesthetic activities.

PubMed

De Melo, Nathalie Ferreira Silva; De Araújo, Daniele Ribeiro; Grillo, Renato; Moraes, Carolina Morales; De Matos, Angélica Prado; de Paula, Eneida; Rosa, André Henrique; Fraceto, Leonardo Fernandes

2012-03-01

This paper describes a comparison of different polymeric nanocapsules (NCs) prepared with the polymers poly(D,L-lactide-co-glycolide), poly(L-lactide) (PLA), and poly(ε-caprolactone) and used as carrier systems for the local anesthetic (LA) benzocaine (BZC). The systems were characterized and their anesthetic activities investigated. The results showed particle size distributions with polydispersity indices below 0.135, average diameters up to 120 nm, zeta potentials up to -30 mV, and entrapment efficiencies around 70%. Formulations of BZC using the polymeric NCs presented slower release profiles, compared with that of free BZC. Slowest release (release constant, k = 0.0016 min(-1)) was obtained using the PLA NC system. Pharmacological evaluation showed that encapsulation of BZC in PLA NCs prolonged its anesthetic action. This new formulation could potentially be used in future applications involving the gradual release of local anesthetics (LAs). Copyright © 2011 Wiley Periodicals, Inc.

Comparative evaluation of endodontic pressure syringe, insulin syringe, jiffy tube, and local anesthetic syringe in obturation of primary teeth: An in vitro study.

PubMed

Hiremath, Mallayya C; Srivastava, Pooja

2016-01-01

The purpose of this in vitro study was to compare four methods of root canal obturation in primary teeth using conventional radiography. A total of 96 root canals of primary molars were prepared and obturated with zinc oxide eugenol. Obturation methods compared were endodontic pressure syringe, insulin syringe, jiffy tube, and local anesthetic syringe. The root canal obturations were evaluated by conventional radiography for the length of obturation and presence of voids. The obtained data were analyzed using Chi-square test. The results showed significant differences between the four groups for the length of obturation (P < 0.05). The endodontic pressure syringe showed the best results (98.5% optimal fillings) and jiffy tube showed the poor results (37.5% optimal fillings) for the length of obturation. The insulin syringe (79.2% optimal fillings) and local anesthetic syringe (66.7% optimal fillings) showed acceptable results for the length of root canal obturation. However, minor voids were present in all the four techniques used. Endodontic pressure syringe produced the best results in terms of length of obturation and controlling paste extrusion from the apical foramen. However, insulin syringe and local anesthetic syringe can be used as effective alternative methods.

Dose-response effects of corneal anesthetics.

PubMed

Polse, K A; Keener, R J; Jauregui, M J

1978-01-01

With double-masking procedures, the dose-response curves for 0.1, 0.2, and 0.4% benoxinate and 0.125, 0.25, and 0.50% proparacaine hydrochloride were determined by monitoring changes in corneal touch threshold after applying each anesthetic. The level of corneal anesthesia necessary for applanation tonometry was also determined. The maximum increase in threshold that could be measured following instillation of 50 microliter of the drug was 200 mg/mm2 All 6 anesthetic solutions produced this amount of decreased corneal sensitivity. Recovery from the anesthetic was exponential for all concentrations; however, the lower doses had the shortest duration. For applanation tonometry, the corneal threshold for touch must be 75 mg/mm2 or higher. We conclude that a quarter to a half of the commonly used anesthetic dose is sufficient for routine tonometric evaluation.

Comparative analysis of tissue reactions to anesthetic solutions: histological analysis in subcutaneous tissue of rats.

PubMed Central

Ribeiro, Paulo Domingos; Sanches, Marcio Giampietro; Okamoto, Tetuo

2003-01-01

Postanesthetic pain is a relatively common complication after local anesthesia. This complication may be caused by the anesthetic technique or by the anesthetic solution used. Tissue reactions induced by the anesthetic solutions may be one of the factors resulting in pain after anesthesia. The objective of this study was to comparatively analyze tissue reactions induced by different anesthetic solutions in the subcutaneous tissue of rats. The following solutions were utilized: 2% lidocaine without vasoconstrictor; a 0.5% bupivacaine solution with 1:200,000 adrenaline; a 4% articaine solution and 2% mepivacaine, both with 1:100,000 adrenaline; and a 0.9% sodium chloride solution as a control. Sterilized absorbent paper cones packed inside polyethylene tubes were soaked in the solutions and implanted in the subcutaneous region. The sacrifice periods were 1, 2, 5, and 10 days after surgery. The specimens were prepared and stained with hematoxylin and eosin for histological analysis. The results showed that there is a difference in tissue irritability produced by the local anesthetic solutions. The results also showed that there is no relation between the concentration of the drug and the inflammatory intensity, that the mepivacaine and articaine solutions promoted less inflammatory reaction than the bupivacaine, and that the lidocaine solution produced the least intense inflammation. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 PMID:14959905

Comparative evaluation of effectiveness of intra-pocket anesthetic gel and injected local anesthesia during scaling and root planing - A split-mouth clinical trial.

PubMed

Chintala, Kalyan; Kumar, Sandhya Pavan; Murthy, K Raja V

2017-01-01

Pain control is an important outcome measure for successful periodontal therapy. Injected local anesthesia has been used to secure anesthesia for scaling and root planing (SRP) and continues to be the anesthetic of choice for pain control. Alternatively, intra-pocket anesthetic gel has been used as an anesthetic during SRP. Hence, this clinical trial was done to compare the effectiveness of intra-pocket anesthetic gel and injected local anesthesia during SRP and also to assess the influence of intra-pocket anesthetic gel on treatment outcomes in chronic periodontitis patients. Fifteen systemically healthy chronic periodontitis patients were recruited. The dental quadrants on right side received either intra-pocket 20% benzocaine gel (Gel group) or infiltration/block by 2% lidocaine with 1:80,000 adrenaline (injection group). Quadrants on the left side received the alternative. Pain perception and patients preference for the type of anesthesia was recorded. Clinical parameters: plaque index, modified gingival index, modified sulcular bleeding index, probing pocket depth, and clinical attachment level were recorded at baseline and 1 month after treatment. No difference was observed in visual analog scale (P > 0.05) and verbal rating scale (P > 0.05) pain perception between gel group and injection group. A slightly increased preference to gel as anesthesia (53% vs. 47%) was observed. The treatment outcome after SRP did not show a significant difference between gel and injection group (P > 0.05). Intra-pocket administration of 20% benzocaine gel may be effective for pain control during SRP and may offer an alternative to conventional injection anesthesia.

Buffered lidocaine and bupivacaine mixture - the ideal local anesthetic solution?

PubMed

Best, Corliss A; Best, Alyssa A; Best, Timothy J; Hamilton, Danielle A

2015-01-01

The use of injectable local anesthetic solutions to facilitate pain-free surgery is an integral component of many procedures performed by the plastic surgeon. In many instances, a solution that has both rapid onset and prolonged duration of analgesia is optimal. A combination of lidocaine and bupivacaine, plain or with epinephrine, is readily available in most Canadian health care settings where such procedures are performed, and fulfills these criteria. However, commercially available solutions of both medications are acidic and cause a burning sensation on injection. Buffering to neutral pH with sodium bicarbonate is a practical method to mitigate the burning sensation, and has the added benefit of increasing the fraction of nonionized lipid soluble drug available. The authors report on the proportions of the three drugs to yield a neutral pH, and the results of an initial survey regarding the use of the combined solution with epinephrine in hand surgery.

Evaluation of cerebrospinal fluid lactate and plasma lactate concentrations in anesthetized dogs with and without intracranial disease

PubMed Central

Caines, Deanne; Sinclair, Melissa; Wood, Darren; Valverde, Alexander; Dyson, Doris; Gaitero, Luis; Nykamp, Stephanie

2013-01-01

The objectives of this study were to establish a reference interval for canine cerebrospinal fluid lactate (CSFL) and to compare CSFL and plasma lactate (PL) concentrations in anesthetized dogs with and without intracranial disease. Using a prospective study, canine blood and cerebrospinal fluid were collected for lactate analysis in 11 dogs with intracranial disease after undergoing magnetic resonance imaging (MRI) (Group ID-MRI), in 10 healthy dogs post-MRI (Group H-MRI), and in 39 healthy dogs after induction of anesthesia (Group H-Sx). Dogs were anesthetized for the procedures using different anesthetic protocols. Neurological scores (NS) and sedation scores (SS) were assessed pre-anesthesia in ID-MRI dogs. The CSFL reference interval [90% confidence interval (CI) for lower and upper limits] was 1.1 (1.0 to 1.2) to 2.0 (2.0 to 2.1) mmol/L. Mean ± SD CSFL concentrations were: ID-MRI, 2.1 ± 0.8; H-MRI, 1.6 ± 0.4; and H-Sx, 1.6 ± 0.2 mmol/L. There was a tendency for higher CSFL in dogs in the ID-MRI group than in those in the H-MRI or H-Sx groups (P = 0.12). There was agreement between CSFL and PL in ID-MRI dogs (P = 0.007), but not in dogs in H-MRI (P = 0.5) or H-Sx (P = 0.2). Of the ID-MRI dogs, those with worse NS had higher CSFL (r2 = 0.44). The correlation between CSFL and PL in dogs with intracranial disease and between worse NS and higher CSFL warrants further investigation into the use of CSFL and PL for diagnostic and prognostic purposes. PMID:24124273

Cardiovascular effects of torcetrapib in conscious and pentobarbital-anesthetized dogs.

PubMed

Polakowski, James S; King, Andrew J; Campbell, Thomas J; Nelson, Richard A; Preusser, Lee C; Kempf-Grote, Anita J; Marsh, Kennan C; Gintant, Gary A; Cox, Bryan F; Mittelstadt, Scott W

2009-12-01

Torcetrapib is a cholesteryl ester transfer protein inhibitor with an undesired response of increasing arterial pressure in humans. Pressor responses to torcetrapib have been demonstrated in multiple preclinical species. However, these studies have not related plasma concentrations to observed effects. Our purpose was to 1) characterize the cardiovascular responses of torcetrapib in conscious and anesthetized dogs with measured plasma concentrations; and 2) characterize the hemodynamic effects contributing to hypertension using comprehensively instrumented anesthetized dogs. Torcetrapib was dosed orally (3, 30 mg/kg) and intravenously (0.01, 0.33, 0.1 mg/kg) in conscious and anesthetized dogs, respectively. Mean arterial pressure and heart rate were monitored in both models; additional parameters were measured in anesthetized dogs. Plasma drug concentrations were assessed in both models. In conscious and anesthetized dogs, torcetrapib increased mean arterial pressure 25 and 18 mm Hg and heart rate 35 and 21 beats/min, at 2.94 and 3.99 microg/mL, respectively. In anesthetized dogs, torcetrapib increased pulmonary arterial pressure, both systemic and pulmonary hypertension driven by increases in vascular resistance. The compound increased rate pressure product and myocardial contractility while decreasing time to systolic pressure recovery and ejection time. Thus, torcetrapib-induced pressor responses are mediated by systemic and pulmonary vasoconstriction and are associated with increased myocardial oxygen consumption and positive inotropy.

Development of a local anesthetic lidocaine-loaded redox-active injectable gel for postoperative pain management.

PubMed

Nagasaki, Yukio; Mizukoshi, Yutaro; Gao, Zhenyu; Feliciano, Chitho P; Chang, Kyungho; Sekiyama, Hiroshi; Kimura, Hiroyuki

2017-07-15

Although local anesthesia is commonly applied for pain relief, there are several issues such as its short duration of action and low effectiveness at the areas of inflammation due to the acidic pH. The presence of excessive amount of reactive oxygen species (ROS) is known to induce inflammation and aggravate pain. To resolve these issues, we developed a redox-active injectable gel (RIG) with ROS-scavenging activity. RIG was prepared by mixing polyamine-b-poly(ethylene glycol)-b-polyamine with nitroxide radical moieties as side chains on the polyamine segments (PMNT-b-PEG-b-PMNT) with a polyanion, which formed a flower-type micelle via electrostatic complexation. Lidocaine could be stably incorporated in its core. When the temperature of the solution was increased to 37°C, the PIC-type flower micelle transformed to gel. The continuous release of lidocaine from the gel was observed for more than three days, without remarkable initial burst, which is probably owing to the stable entrapment of lidocaine in the PIC core of the gel. We evaluated the analgesic effect of RIG in carrageenan-induced arthritis mouse model. Results showed that lidocaine-loaded RIG has stronger and longer analgesic effect when administered in inflamed areas. In contrast, while the use of non-complexed lidocaine did not show analgesic effect one day after its administration. Note that no effect was observed when PIC-type flower micelle without ROS-scavenging ability was used. These findings suggest that local anesthetic-loaded RIG can effectively reduce the number of injection times and limit the side effects associated with the use of anti-inflammatory drugs for postoperative pain management. 1. We have been working on nanomaterials, which effectively eliminate ROS, avoiding dysfunction of mitochondria in healthy cells. 2. We designed redox injectable gel using polyion complexed flower type micelle, which can eliminates ROS locally. 3. We could prepare local anesthesia-loaded redox injectable

EFFECTS OF TRAMADOL ON THE MINIMUM ANESTHETIC CONCENTRATION OF ISOFLURANE IN WHITE-EYED PARAKEETS (PSITTACARA LEUCOPHTHALMUS).

PubMed

Escobar, André; da Rocha, Rozana Wendler; Midon, Monica; de Almeida, Ricardo Miyasaka; Filho, Darcio Zangirolami; Werther, Karin

2017-06-01

The aim of this study was to determine the minimum anesthetic concentration (MAC) of isoflurane, and to investigate if tramadol changes the isoflurane MAC in white-eyed parakeets (Psittacara leucophthalmus). Ten adult birds weighing 157 ± 9 g were anesthetized with isoflurane in oxygen under mechanical ventilation. Isoflurane concentration for the first bird was adjusted to 2.2%, and after 15 min an electrical stimulus was applied in the thigh area to observe the response (movement or nonmovement). Isoflurane concentration for the subsequent bird was increased by 10% if the previous bird moved, or decreased by 10% if the previous bird did not move. This procedure was performed serially until at least four sequential crossover events were detected. A crossover event was defined as a sequence of two birds with different responses (positive or negative) to the electrical stimulus. Isoflurane MAC was calculated as the mean isoflurane concentration value at the crossover events. After 1 wk, the same birds were reanesthetized with isoflurane and MAC was determined at 15 and 30 min after intramuscular administration of 10 mg/kg of tramadol using the same method. A paired t-test (P < 0.05%) was used to detect significant differences for MAC between treatments. Isoflurane MAC in this population of white-eyed parakeets was 2.47 ± 0.09%. Isoflurane MAC values 15 and 30 min after tramadol administration were indistinguishable from each other (pooled value was 2.50 ± 0.18%); they were also indistinguishable from isoflurane MAC without tramadol. The isoflurane MAC value in white-eyed parakeets is higher than reported for other bird species. Tramadol (10 mg/kg, i.m.) does not change isoflurane MAC in these birds.

Effects of surgery and anesthetic choice on immunosuppression and cancer recurrence.

PubMed

Kim, Ryungsa

2018-01-18

The relationship between surgery and anesthetic-induced immunosuppression and cancer recurrence remains unresolved. Surgery and anesthesia stimulate the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS) to cause immunosuppression through several tumor-derived soluble factors. The potential impact of surgery and anesthesia on cancer recurrence was reviewed to provide guidance for cancer surgical treatment. PubMed was searched up to December 31, 2016 using search terms such as, "anesthetic technique and cancer recurrence," "regional anesthesia and cancer recurrence," "local anesthesia and cancer recurrence," "anesthetic technique and immunosuppression," and "anesthetic technique and oncologic surgery." Surgery-induced stress responses and surgical manipulation enhance tumor metastasis via release of angiogenic factors and suppression of natural killer (NK) cells and cell-mediated immunity. Intravenous agents such as ketamine and thiopental suppress NK cell activity, whereas propofol does not. Ketamine induces T-lymphocyte apoptosis but midazolam does not affect cytotoxic T-lymphocytes. Volatile anesthetics suppress NK cell activity, induce T-lymphocyte apoptosis, and enhance angiogenesis through hypoxia inducible factor-1α (HIF-1α) activity. Opioids suppress NK cell activity and increase regulatory T cells. Local anesthetics such as lidocaine increase NK cell activity. Anesthetics such as propofol and locoregional anesthesia, which decrease surgery-induced neuroendocrine responses through HPA-axis and SNS suppression, may cause less immunosuppression and recurrence of certain types of cancer compared to volatile anesthetics and opioids.

Anesthetic management during cardiopulmonary bypass: a systematic review.

PubMed

Barry, Aaron E; Chaney, Mark A; London, Martin J

2015-04-01

Cardiopulmonary bypass (CPB) required for cardiac surgery presents unique challenges to the cardiac anesthesiologist responsible for providing the 3 most basic facets of any anesthetic: amnesia, analgesia, and muscle relaxation. Unique pathophysiologic changes during CPB result in pharmacokinetic alterations that impact the serum and tissue concentrations of IV and volatile anesthetics. Similarly, CPB causes pharmacodynamic alterations that impact anesthetic efficacy. The clinical significance of these alterations represents a "moving target" as practice evolves and the technology of CPB circuitry advances. In addition, perfusionists choose, modify, and maintain the CPB circuitry and membrane oxygenator. Thus, their significance may not be fully appreciated by the anesthesiologist. These issues have a profound impact on the anesthetic state of the patient. The delivery and maintenance of anesthesia during CPB present unique challenges. The perfusionist may be directly responsible for the delivery of anesthetic during CPB, a situation unique to the cardiac suite. In addition, monitors of anesthetic depth-assessment of clinical signs, hemodynamic indicators, the bispectral index monitor, end-tidal anesthetic concentration, or twitch monitoring-are often absent, unreliable, or directly impacted by the unique pathophysiology associated with CPB. The magnitude of these challenges is reflected in the higher incidence of intraoperative awareness during cardiac surgery. Further complicating matters are the lack of specific clinical guidelines and varying international policies regarding medical device specifications that add further layers of complexity and introduce practice variability both within institutions and among nations. We performed a systematic survey of the literature to identify where anesthetic practice during CPB is evidence based (or not), identify gaps in the literature to guide future investigations, and explore the implications of evolving surgical

Real-time evaluation of diffusion of the local anesthetic solution during peribulbar block using ultrasound imaging and clinical correlates of diffusion.

PubMed

Luyet, Cédric; Eng, Kenneth T; Kertes, Peter J; Avila, Arsenio; Muni, Rajeev H; McHardy, Paul

2012-01-01

The aims of this prospective observational study were to assess the incidence of intraconal spread during peribulbar (extraconal) anesthesia by real-time ultrasound imaging of the retro-orbital compartment and to determine whether a complete sensory and motor block (with akinesia) of the eye is directly related to the intraconal spread. Ultrasound imaging was performed in 100 patients who underwent a surgical procedure on the posterior segment of the eye. All patients received a peribulbar block using the inferolateral approach. Once the needle was in place, a linear ultrasound transducer was placed over the eyelid and the spread of local anesthetics was assessed during the injection (real time). Akinesia was assessed by a blinded observer 10 minutes after block placement. The incidence of intraconal spread and its correlation with a complete akinesia was measured. The overall block failure rate was 28% in terms of akinesia, and the rate of rescue blocks was 20%. Clear intraconal spread during injection of the local anesthetic mixture could be detected with ultrasound imaging in 61 of 100 patients. The positive predictive value for successful block when intraconal spread was detected was 98% (95% confidence interval, 91%-100%). The association between clear and no evidence of intraconal spread and effective block was statistically significant (χ test, P < 0.001). Ultrasound imaging provides information of local anesthetic spread within the retro-orbital space, which might assist in the prediction of block success.

The Effect of Local Anesthetic Infiltration Around Nephrostomy Tract on Postoperative Pain Control after Percutaneous Nephrolithotomy: A Systematic Review and Meta-Analysis.

PubMed

Wang, Jiawu; Zhang, Chengyao; Tan, Dan; Tan, Guangzhong; Yang, Bo; Chen, Wenkai; Tang, Guoqiang

2016-01-01

To assess the safety and efficacy of local anesthetic infiltration around nephrostomy tract on postoperative pain control after percutaneous nephrolithotomy. This systematic review was performed based on randomized clinic trials about local anesthetic infiltration around nephrostomy tract on postoperative pain control. The weighted mean difference (WMD), with their corresponding 95% CI, was calculated to compare continuous variables. Our results showed that the consumption of analgesic was less in the experimental group than in the control group (WMD -25.32, 95% CI -48.09 to -2.55, p = 0.003). There was no significant difference between the mean Visual Analog Scale (VAS) in the experimental group than the control group after 6 h while significantly lower after 24 h. The time of first analgesic demand was significantly longer in the experimental group (WMD 2.19, 95% CI 0.98-3.41). There was no significant difference between 2 groups in terms of operation time, hemoglobin (Hb) alteration, and hospital stay. Local anesthetic infiltration around nephrostomy tract had similar efficacy in the control group in terms of operation time, Hb alteration, and hospital stay, but offers some potential advantages in terms of analgesia requirement, the time of first analgesic demand, and VAS-24 h. However, good quality and large studies with long-term follow-up are warranted for further research. © 2016 S. Karger AG, Basel.

Performance of an electrochemical carbon monoxide monitor in the presence of anesthetic gases.

PubMed

Dunning, M; Woehlck, H J

1997-11-01

The passage of volatile anesthetic agents through accidentally dried CO2 absorbents in anesthesia circuits can result in the chemical breakdown of anesthetics with production of greater than 10000 ppm carbon monoxide (CO). This study was designed to evaluate a portable CO monitor in the presence of volatile anesthetic agents. Two portable CO monitors employing electrochemical sensors were tested to determine the effects of anesthetic agents, gas sample flow rates, and high CO concentrations on their electrochemical sensor. The portable CO monitors were exposed to gas mixtures of 0 to 500 ppm CO in either 70% nitrous oxide, 1 MAC concentrations of contemporary volatile anesthetics, or reacted isoflurane or desflurane (containing CO and CHF3) in oxygen. The CO measurements from the electrochemical sensors were compared to simultaneously obtained samples measured by gas chromatography (GC). Data were analyzed by linear regression. Overall correlation between the portable CO monitors and the GC resulted in an r2 value >0.98 for all anesthetic agents. Sequestered samples produced an exponential decay of measured CO with time, whereas stable measurements were maintained during continuous flow across the sensor. Increasing flow rates resulted in higher CO readings. Exposing the CO sensor to 3000 and 19000 ppm CO resulted in maximum reported concentrations of approximately 1250 ppm, with a prolonged recovery. Decrease in measured concentration of the sequestered samples suggests destruction of the sample by the sensor, whereas a diffusion limitation is suggested by the dependency of measured value upon flow. Any value over 500 ppm must be assumed to represent dangerous concentrations of CO because of the non-linear response of these monitors at very high CO concentrations. These portable electrochemical CO monitors are adequate to measure CO concentrations up to 500 ppm in the presence of typical clinical concentrations of anesthetics.

Use of anesthetics associated to vasoconstrictors for dentistry in patients with cardiopathies. Review of the literature published in the last decade

PubMed Central

Serrera Figallo, María A.; Velázquez Cayón, Rocío T.; Corcuera Flores, Jose R.; Machuca Portillo, Guillermo

2012-01-01

Objective: The use of local anesthetics associated to vasoconstrictor agents in dentistry is thoroughly justified and is widely extended, but we cannot ignore the fact that anesthetic infiltration poses risk of complications throughout the dental treatment period. The objective of the present review is to document the reported effects the use of the local anesthetics most widely employed in dentistry, with or without association to vasoconstrictor agents may have in patients with any sort of cardiopathy. Study Design: We have searched for randomized clinical trials on the assessment of the cardiovascular effects of local anesthetics used in dentistry, without limits as regards age or sex, conducted in patients with any type of cardiopathy which were published during the last decade and were index-linked in Cochrane, Embase and Medline. Results: We have found six randomized clinical trials index-linked in Medline and Cochrane in the past ten years. These trials compare different types of anesthetics: lidocaine 2%, mepivacaine 2%, prilocaine 2% , associated or not to different vasoconstrictor concentrations such as adrenaline or felypressin. The cardiopathies affecting the patients included in the different trials range from hypertension, ischemic heart disease, arrythmias, chronic coronary disease to heart transplantation. Conclusions: The use of anesthetics associated to vasoconstrictor agents is justified in the case of patients with cardiopathies (once we get over the period in which any type of dental manipulation is contraindicated) and in controlled hypertensive patients. In any case, we must be very careful with the choice and execution of the anesthetic technique, being it possible to use a dose between 1.8 and 3.6 ml, on a general basis. Further studies are necessary to establish the effects of these drugs on severe hypertensive patients or in patients with other more advanced cardiopathies. Key words:Vasoconstrictor agents, epinephrine/adverse effects

Predictive accuracy of a model of volatile anesthetic uptake.

PubMed

Kennedy, R Ross; French, Richard A; Spencer, Christopher

2002-12-01

A computer program that models anesthetic uptake and distribution has been in use in our department for 20 yr as a teaching tool. New anesthesia machines that electronically measure fresh gas flow rates and vaporizer settings allowed us to assess the performance of this model during clinical anesthesia. Gas flow, vaporizer settings, and end-tidal concentrations were collected from the anesthesia machine (Datex S/5 ADU) at 10-s intervals during 30 elective anesthetics. These were entered into the uptake model. Expired anesthetic vapor concentrations were calculated and compared with actual values as measured by the patient monitor (Datex AS/3). Sevoflurane was used in 16 patients and isoflurane in 14 patients. For all patients, the median performance error was -0.24%, the median absolute performance error was 13.7%, divergence was 2.3%/h, and wobble was 3.1%. There was no significant difference between sevoflurane and isoflurane. This model predicted expired concentrations well in these patients. These results are similar to those seen when comparing calculated and actual propofol concentrations in propofol infusion systems and meet published guidelines for the accuracy of models used in target-controlled anesthesia systems. This model may be useful for predicting responses to changes in fresh gas and vapor settings. We compared measured inhaled anesthetic concentrations with those predicted by a model. The method used for comparison has been used to study models of propofol administration. Our model predicts expired isoflurane and sevoflurane concentrations at least as well as common propofol models predict arterial propofol concentrations.

Effect of four local anesthetics (tetracaine, proparacaine, lidocaine, and bupivacaine) on intraocular pressure in dogs.

PubMed

Sarchahi, Ali Asghar; Eskandari, Mehdi

2018-06-23

To measure IOP in animals, it is often necessary to use topical anesthetics. The use of these drugs may cause changes in IOP and interfere with the final results. To address this issue, the effects of four local anesthetics (tetracaine, proparacaine, lidocaine, and bupivacaine) on IOP were investigated in ten adult dogs. One drop of tetracaine was instilled in the right eye of half of the dogs and in the left eye of the other dogs; normal saline was instilled in the fellow eyes. The IOP in each dog was measured before and at 0, 5, 10, 15, 20, 25, 30, and 35 min after drug instillation using an electronic rebound tonometer. The effects of the other anesthetics were studied in the same way at intervals of at least 1 week. After instillation of tetracaine, the IOP decreased gradually, such that after 15 min, the IOP was significantly lower than the baseline (p = 0.022) and control values (p = 0.048). Proparacaine also reduced IOP after 10 min compared to baseline values (p = 0.046), but the two other drugs, bupivacaine and lidocaine, had no significant effect on IOP. The duration of eye anesthesia was 16, 20, 22, and 34 min for tetracaine, lidocaine, bupivacaine, and proparacaine, respectively. We recommend using drugs that combine inducing longer anesthesia with producing the smallest change in IOP, such as bupivacaine and, subsequently, lidocaine. Tetracaine and proparacaine have a significant effect on IOP, and if these drugs are used, this effect should be considered.

Use of intravenous lipid emulsion to reverse central nervous system toxicity of an iatrogenic local anesthetic overdose in a patient on peritoneal dialysis.

PubMed

Lange, D Bruce; Schwartz, Daniel; DaRoza, Gerald; Gair, Robert

2012-12-01

To describe a case of severe central nervous system toxicity after an overdose of lidocaine by local infiltration in a peritoneal dialysis patient and subsequent treatment of the toxicity with lipid emulsion. A 31-year-old male received an iatrogenic overdose of 1600 mg of lidocaine 2% by infiltration during an attempt to remove and replace a peritoneal dialysis catheter. Within 10 minutes after the last lidocaine injection, the patient exhibited features of local anesthetic toxicity, which included tachycardia, hypertension, shortness of breath, dizziness, and a choking sensation that progressed to hallucinations, dysarthria, and uncoordinated, weak limb movement. Within 10 minutes after administration of a single 1.5-mg/kg intravenous bolus of 1.5 mL/kg [corrected], the patient improved dramatically. After observation overnight in a monitored care setting, the patient was discharged home with no apparent neurologic sequelae. Systemic toxicity due to regional anesthesia with local anesthetic agents such as lidocaine has been well described in the medical literature. The use of lipid emulsion as an antidote to the toxicity of local anesthetics and other lipophilic drugs has been suggested as a valuable intervention in both early, rapidly progressive toxicity, as well as toxicity that is refractory to standard treatment. Patients with advanced chronic kidney disease may be more susceptible to systemic effects of lidocaine due to decreased drug elimination. Central nervous system toxicity due to an overdose of lidocaine was quickly reversed by intravenous lipid emulsion in our patient.

Continuous Transversus Abdominis Plane Nerve Blocks: Does Varying Local Anesthetic Delivery Method-Automatic Repeated Bolus Versus Continuous Basal Infusion-Influence the Extent of Sensation to Cold?: A Randomized, Triple-Masked, Crossover Study in Volunteers.

PubMed

Khatibi, Bahareh; Said, Engy T; Sztain, Jacklynn F; Monahan, Amanda M; Gabriel, Rodney A; Furnish, Timothy J; Tran, Johnathan T; Donohue, Michael C; Ilfeld, Brian M

2017-04-01

administration technique (continuous basal versus hourly bolus) when using ropivacaine 0.2% and TAP catheters at 8 mL/h and 24 mL every 3 hours significantly influences the cutaneous effects after 6 hours of administration. Additional research is required to determine whether changing variables (eg, local anesthetic concentration, basal infusion rate, bolus dose volume, and/or interval) would provide different results.

Detomidine reduces isoflurane anesthetic requirement (MAC) in horses.

PubMed

Steffey, Eugene P; Pascoe, Peter J

2002-10-01

To quantitate the dose- and time-related magnitude of the anesthetic sparing effect of, and selected physiological responses to detomidine during isoflurane anesthesia in horses. Randomized cross-over study. Three, healthy, young adult horses weighing 485 ± 14 kg. Horses were anesthetized on two occasions to determine the minimum alveolar concentration (MAC) of isoflurane in O 2 and then to measure the anesthetic sparing effect (time-related MAC reduction) following IV detomidine (0.03 and 0.06 mg kg -1 ). Selected common measures of cardiopulmonary function, blood glucose and urinary output were also recorded. Isoflurane MAC was 1.44 ± 0.07% (mean ± SEM). This was reduced by 42.8 ± 5.4% and 44.8 ± 3.0% at 83 ± 23 and 125 ± 36 minutes, respectively, following 0.03 and 0.06 mg kg -1 , detomidine. The MAC reduction was detomidine dose- and time-dependent. There was a tendency for mild cardiovascular and respiratory depression, especially following the higher detomidine dose. Detomidine increased both blood glucose and urine flow; the magnitude of these changes was time- and dose-dependent CONCLUSIONS: Detomidine reduces anesthetic requirement for isoflurane and increases blood glucose concentration and urine flow in horses. These changes were dose- and time-related. The results imply potent anesthetic sparing actions by detomidine. The detomidine-related increased urine flow should be considered in designing anesthetic protocols for individual horses. Copyright © 2002 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.

Comparing the effects of single shot sciatic nerve block versus posterior capsule local anesthetic infiltration on analgesia and functional outcome after total knee arthroplasty: a prospective, randomized, double-blinded, controlled trial.

PubMed

Safa, Ben; Gollish, Jeffrey; Haslam, Lynn; McCartney, Colin J L

2014-06-01

Peripheral nerve blocks appear to provide effective analgesia for patients undergoing total knee arthroplasty. Although the literature supports the use of femoral nerve block, addition of sciatic nerve block is controversial. In this study we investigated the value of sciatic nerve block and an alternative technique of posterior capsule local anesthetic infiltration analgesia. 100 patients were prospectively randomized into three groups. Group 1: sciatic nerve block; Group 2: posterior local anesthetic infiltration; Group 3: control. All patients received a femoral nerve block and spinal anesthesia. There were no differences in pain scores between groups. Sciatic nerve block provided a brief clinically insignificant opioid sparing effect. We conclude that sciatic nerve block and posterior local anesthetic infiltration do not provide significant analgesic benefits. Copyright © 2014 Elsevier Inc. All rights reserved.

[Evaluation of vaporizers by anesthetic gas monitors corrected with a new method for preparation of calibration gases].

PubMed

Kurashiki, T

1996-11-01

For resolving the discrepancy of concentrations found among anesthetic gas monitors, the author proposed a new method using a vaporizer as a standard anesthetic gas generator for calibration. In this method, the carrier gas volume is measured by a mass flow meter (SEF-510 + FI-101) installed before the inlet of the vaporizer. The vaporized weight of volatile anesthetic agent is simultaneously measured by an electronic force balance (E12000S), on which the vaporizer is placed directly. The molar percent of the anesthetic is calculated using these data and is transformed into the volume percent. These gases discharging from the vaporizer are utilized for calibrating anesthetic gas monitors. These monitors are normalized by the linear equation describing the relationship between concentrations of calibration gases and readings of the anesthetic gas monitors. By using normalized monitors, flow rate-concentration performance curves of several anesthetic vaporizers were obtained. The author concludes that this method can serve as a standard in evaluating anesthetic vaporizers.

Actions of Bupivacaine, a Widely Used Local Anesthetic, on NMDA Receptor Responses

PubMed Central

Paganelli, Meaghan A.

2015-01-01

NMDA receptors mediate excitatory neurotransmission in brain and spinal cord and play a pivotal role in the neurological disease state of chronic pain, which is caused by central sensitization. Bupivacaine is the indicated local anesthetic in caudal, epidural, and spinal anesthesia and is widely used clinically to manage acute and chronic pain. In addition to blocking Na+ channels, bupivacaine affects the activity of many other channels, including NMDA receptors. Importantly, bupivacaine inhibits NMDA receptor-mediated synaptic transmission in the dorsal horn of the spinal cord, an area critically involved in central sensitization. We used recombinant NMDA receptors expressed in HEK293 cells and found that increasing concentrations of bupivacaine decreased channel open probability in GluN2 subunit- and pH-independent manner by increasing the mean duration of closures and decreasing the mean duration of openings. Using kinetic modeling of one-channel currents, we attributed the observed current decrease to two main mechanisms: a voltage-dependent “foot-in-the-door” pore block and an allosteric gating effect. Further, the inhibition was state-independent because it occurred to the same degree whether the drug was applied before or after glutamate stimulation and was mediated by extracellular and intracellular inhibitory sites, via hydrophilic and hydrophobic pathways. These results predict that clinical doses of bupivacaine would decrease the peak and accelerate the decay of synaptic NMDA receptor currents during normal synaptic transmission. These quantitative predictions inform possible applications of bupivacaine as preventative and therapeutic approaches in chronic pain. PMID:25589775

Local anesthetic-induced inhibition of human neutrophil priming: the influence of structure, lipophilicity, and charge.

PubMed

Picardi, Susanne; Cartellieri, Sibylle; Groves, Danja; Hahnenkamp, Klaus; Hahnenekamp, Klaus; Gerner, Peter; Durieux, Marcel E; Stevens, Markus F; Lirk, Philipp; Hollmann, Markus W

2013-01-01

Local anesthetics (LAs) are widely known for inhibition of voltage-gated sodium channels underlying their antiarrhythmic and antinociceptive effects. However, LAs have significant immunomodulatory properties and were shown to affect human neutrophil functions independent of sodium-channel blockade. Previous studies suggest a highly selective interaction between LAs and the α-subunit of G protein-coupled receptors of the Gq/G11 family as underlying mechanism. Providing a detailed structure function analysis, this study aimed to determine the active parts within the LA molecule responsible for the effects on human neutrophil priming. Human neutrophils were incubated with structurally different LAs for 60 minutes, followed by priming and activation using either platelet-activating factor or lysophosphatidic acid and N-formyl-methionyl-L-leucyl-L-phenylalanine. Superoxide anion generation was determined, using the cytochrome c reduction assay. Differences in priming inhibition of human neutrophils between LAs were smaller than expected, although significant. Ester-linked LAs blocked priming responses more effectively than did amide LAs. Furthermore, the inhibitory potency of LAs on priming decreased with an increase of their respective octanol-buffer coefficient, and inhibition did not correlate with sodium-channel-blocking potency. Charge was not crucially required for priming inhibition, yet it played a role in effect size. Local anesthetics significantly attenuated Gαq-protein-mediated neutrophil priming. The most potent inhibition was achieved by ester compounds, inversely correlated with their octanol-buffer coefficient, and enhanced by permanent charges within the LA molecule. No correlation to their potency of blocking sodium channels was found.

Lysine-based surfactants as chemical permeation enhancers for dermal delivery of local anesthetics.

PubMed

Teixeira, Raquel S; Cova, Tânia F G G; Silva, Sérgio M C; Oliveira, Rita; Araújo, Maria J; Marques, Eduardo F; Pais, Alberto A C C; Veiga, Francisco J B

2014-10-20

The aim of this study is to investigate the efficacy of new, biocompatible, lysine-based surfactants as chemical permeation enhancers for two different local anesthetics, tetracaine and ropivacaine hydrochloride, topically administered. Results show that this class of surfactants strongly influences permeation, especially in the case of the hydrophilic and ionized drug, ropivacaine hydrochloride, that is not easily administered through the stratum corneum. It is also seen that the selected permeation enhancers do not have significant deleterious effects on the skin structure. A cytotoxicity profile for each compound was established from cytotoxicity studies. Molecular dynamics simulation results provided a rationale for the experimental observations, introducing a mechanistic view of the action of the surfactants molecules upon lipid membranes. Copyright © 2014. Published by Elsevier B.V.

Chronological Changes in Ropivacaine Concentration and Analgesic Effects Between Transversus Abdominis Plane Block and Rectus Sheath Block.

PubMed

Murouchi, Takeshi; Iwasaki, Soshi; Yamakage, Michiaki

2015-01-01

Transversus abdominis plane block (TAPB) and rectus sheath block (RSB) are popular methods of controlling postoperative pain. Chronological changes in blood concentrations of local anesthetics have not been described, although a large amount of local anesthetic is required to block these compartments. We postulated that blood concentrations of anesthetics would peak earlier during TAPB than RSB (primary end point). Secondary end points were elapsed time from block until first postoperative rescue analgesia and affected dermatomes. This prospective, randomized study included 22 patients scheduled for laparoscopic ovarian surgery under general anesthesia. The patients were randomized to receive either a bilateral single-shot TAPB or a bilateral RSB (15 mL of 0.5% ropivacaine per side). Arterial blood was sampled 10, 20, 30, 45, 60, 90, and 120 minutes after ropivacaine administration. This trial was registered at the UMIN-Clinical Trials Registry (UMIN000012133) before patient recruitment. Arterial ropivacaine levels after block peaked earlier in the TAPB than in RSB [Tmax: 35 (12) vs 53 (16) minutes; P = 0.02], whereas peak ropivacaine concentrations did not significantly differ between the groups [Cmax: 1.83 (0.41) vs 1.79 (0.33) μg/mL; P = 0.54]. Peak ropivacaine concentrations exceeded 2.2 μg/mL in 1 and 2 patients in the RSB and TAPB groups, respectively, although symptoms of local anesthetic systemic toxicity were not evident in any of them. The median [interquartile range] duration of analgesia was significantly longer for TAPB than RSB (421 [335-536] vs 196 [168-277] minutes; P = 0.01). Peak ropivacaine concentrations were comparable during TAPB and RSB, but peaked earlier during TAPB. Although 150 mg of ropivacaine remained effective significantly longer during TAPB than RSB during laparoscopic surgery, this dose could cause local anesthetic systemic toxicity. The analgesic effects of blocks with less ropivacaine should be assessed.

Variability in anesthetic considerations for arteriovenous fistula creation.

PubMed

Siracuse, Jeffrey J; Gill, Heather L; Parrack, Inkyong; Huang, Zhen S; Schneider, Darren B; Connolly, Peter H; Meltzer, Andrew J

2014-01-01

Anesthetic options for arteriovenous fistula (AVF) creation include regional anesthesia (RA), general anesthesia (GA) and local anesthetic for select cases. In addition to the benefits of avoiding GA in high-risk patients, recent studies suggest that RA may increase perioperative venous dilation and improve maturation. Our objective was to assess perioperative outcomes of AVF creation with respect to anesthetic modality and identify patient-level factors associated with variation in contemporary anesthetic selection. National Surgical Quality Improvement Project (NSQIP) data (2007-2010) were accessed to identify patients undergoing AVF creation. Univariate analysis and multivariate logistic regression were performed to assess the relationships among patient characteristics, anesthesia modality and outcome. Of 1,540 patients undergoing new upper extremity AVF creation, 52% were male and 81% were younger than 75 years. Anesthesia distribution was GA in 85.2%, local/monitored anesthetic care (MAC) in 2.9% and RA in 11.9% of cases. By multivariate analysis, independent predictors of RA were dyspnea at rest (hazard ratio [HR] 2.3, 95% confidence interval [CI] 1.1-4.9), age >75 (HR 1.6, 95% CI 1.1-2.3) and teaching hospital status as indicated by housestaff involvement (HR 3.7, 95% CI 2.5-5.5). RA was associated with higher total operative time, duration of anesthesia, length of time in operating room and duration of anesthesia start until surgery start (p<0.01). There were no differences between perioperative complications or mortality among anesthetic modalities, although all deaths occurred in the GA group. Despite recent reports highlighting potential benefits of RA for AVF creation, GA was surprisingly used in the vast majority of cases in the United States. The only comorbidities associated with preferential RA use were advanced age and dyspnea at rest. Practice environment may influence anesthetic selection for these cases, as a nonteaching environment was

Efficacy of Benzocaine, Eugenol and Menthol as Anesthetics for Freshwater Angelfish (Pterophyllum scalare).

PubMed

de Souza Romaneli, Rafael; Boaratti, André Zuffo; Tellechea Rodrigues, Andressa; de Almeida Ueiroz, Daniel Monge; Khan, Kifayat Ullah; Nascimento, Thiago Matias Torres; Fernandes, João Batista Kochenborger

2018-05-29

For the production and commercialization of ornamental fish species, it is indispensable to collect biometric data for the selection of animals for trade and genetic improvement of the stock. However, during handling processes, fishes receive more stress if proper anesthetics are not used. Thus, using appropriate anesthetics is an important tool for minimizing stress in animals. The objective of this study was to determine the effective concentrations of benzocaine, eugenol and menthol for angelfish (Pterophyllum scalare) anesthesia and to develop induction and recovery response curves for different concentrations of these anesthetics. A total of 75 fish were exposed to five concentrations of three different anesthetics, benzocaine (60, 85, 110, 135 and 160 mg L -1 ), eugenol (40, 80, 120, 160 and 200 mg L -1 ) and menthol (50, 75, 150, 200 and 250 mg L -1 ) in a completely randomized design. Each concentration (5 fish per concentration) consisted of five replicates and each replicate was represented by a single fish (1 fish per replicate). The results indicate that the tested substances have met the criteria of anesthetic efficiency. The effective concentrations of benzocaine, eugenol and menthol determined to be 89.25 mg L -1 , 90.6 mg L -1 and 92.1 mg L -1 , respectively for the anesthesia of freshwater angelfish. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Anesthetic synergy between two n-alkanes.

PubMed

Brosnan, Robert J; Fukushima, Fabíola B; Pham, Trung L

2017-05-01

N-butane and n-pentane can both produce general anesthesia. Both compounds potentiate γ-aminobutyric acid type A (GABA A ) receptor function, but only butane inhibits N-methyl-d-aspartate (NMDA) receptors. It was hypothesized that butane and pentane would exhibit anesthetic synergy due to their different actions on ligand-gated ion channels. Prospective experimental study. A total of four Xenopus laevis frogs and 43 Sprague-Dawley rats. Alkane concentrations for all studies were determined via gas chromatography. Using a Xenopus oocyte expression model, standard two-electrode voltage clamp techniques were used to measure NMDA and GABA A receptor responses in vitro as a function of butane and pentane concentrations relevant to anesthesia. The minimum alveolar concentrations (MAC) of butane and pentane were measured separately in rats, and then pentane MAC was measured during coadministration of 0.25, 0.50 or 0.75 times MAC of butane. An isobole with 95% confidence intervals was constructed using regression analysis. A sum of butane and pentane that was statistically less than the lower-end confidence bound isobole indicated a synergistic interaction. Both butane and pentane dose-dependently potentiated GABA A receptor currents over the study concentration range. Butane dose-dependently inhibited NMDA receptor currents, but pentane did not modulate NMDA receptors. Butane and pentane MAC in rats was 39.4±0.7 and 13.7±0.4 %, respectively. A small but significant (p<0.03) synergistic anesthetic effect with pentane was observed during administration of either 0.50 or 0.75×MAC butane. Butane and pentane show synergistic anesthetic effects in vivo consistent with their different in vitro receptor effects. Findings support the relevance of NMDA receptors in mediating anesthetic actions for some, but not all, inhaled agents. Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd

Anesthetic agent-specific effects on synaptic inhibition.

PubMed

MacIver, M Bruce

2014-09-01

Anesthetics enhance γ-aminobutyric acid (GABA)-mediated inhibition in the central nervous system. Different agents have been shown to act on tonic versus synaptic GABA receptors to different degrees, but it remains unknown whether different forms of synaptic inhibition are also differentially engaged. With this in mind, we tested the hypothesis that different types of GABA-mediated synapses exhibit different anesthetic sensitivities. The present study compared effects produced by isoflurane, halothane, pentobarbital, thiopental, and propofol on paired-pulse GABAA receptor-mediated synaptic inhibition. Effects on glutamate-mediated facilitation were also studied. Synaptic responses were measured in rat hippocampal brain slices. Orthodromic paired-pulse stimulation was used to assess anesthetic effects on either glutamate-mediated excitatory inputs or GABA-mediated inhibitory inputs to CA1 neurons. Antidromic stimulation was used to assess anesthetic effects on CA1 background excitability. Agents were studied at equieffective concentrations for population spike depression to compare their relative degree of effect on synaptic inhibition. Differing degrees of anesthetic effect on paired-pulse facilitation at excitatory glutamate synapses were evident, and blocking GABA inhibition revealed a previously unseen presynaptic action for pentobarbital. Although all 5 anesthetics depressed synaptically evoked excitation of CA1 neurons, the involvement of enhanced GABA-mediated inhibition differed considerably among agents. Single-pulse inhibition was enhanced by propofol, thiopental, and pentobarbital, but only marginally by halothane and isoflurane. In contrast, isoflurane enhanced paired-pulse inhibition strongly, as did thiopental, but propofol, pentobarbital, and halothane were less effective. These observations support the idea that different GABA synapses use receptors with differing subunit compositions and that anesthetics exhibit differing degrees of selectivity for

Binding site and affinity prediction of general anesthetics to protein targets using docking.

PubMed

Liu, Renyu; Perez-Aguilar, Jose Manuel; Liang, David; Saven, Jeffery G

2012-05-01

The protein targets for general anesthetics remain unclear. A tool to predict anesthetic binding for potential binding targets is needed. In this study, we explored whether a computational method, AutoDock, could serve as such a tool. High-resolution crystal data of water-soluble proteins (cytochrome C, apoferritin, and human serum albumin), and a membrane protein (a pentameric ligand-gated ion channel from Gloeobacter violaceus [GLIC]) were used. Isothermal titration calorimetry (ITC) experiments were performed to determine anesthetic affinity in solution conditions for apoferritin. Docking calculations were performed using DockingServer with the Lamarckian genetic algorithm and the Solis and Wets local search method (http://www.dockingserver.com/web). Twenty general anesthetics were docked into apoferritin. The predicted binding constants were compared with those obtained from ITC experiments for potential correlations. In the case of apoferritin, details of the binding site and their interactions were compared with recent cocrystallization data. Docking calculations for 6 general anesthetics currently used in clinical settings (isoflurane, sevoflurane, desflurane, halothane, propofol, and etomidate) with known 50% effective concentration (EC(50)) values were also performed in all tested proteins. The binding constants derived from docking experiments were compared with known EC(50) values and octanol/water partition coefficients for the 6 general anesthetics. All 20 general anesthetics docked unambiguously into the anesthetic binding site identified in the crystal structure of apoferritin. The binding constants for 20 anesthetics obtained from the docking calculations correlate significantly with those obtained from ITC experiments (P = 0.04). In the case of GLIC, the identified anesthetic binding sites in the crystal structure are among the docking predicted binding sites, but not the top ranked site. Docking calculations suggest a most probable binding site

Calcium-Binding Properties of Sarcoplasmic Reticulum As Influenced by ATP, Caffeine, Quinine, and Local Anesthetics

PubMed Central

Carvalho, Arselio P.

1968-01-01

Calcium retained at binding sites of the sarcoplasmic reticulum membranes isolated from rabbit skeletal muscle requires 10-5 – 10-4 M ATP to exchange with 45Ca added to the medium. The ATP requirement for Ca exchangeability was observed with respect to the "intrinsic" Ca of the reticulum membranes and the fraction of Ca that is "actively" bound in the presence of ATP. Furthermore, a concentration of free Ca in the medium higher than 10-8 M is required for ATP to promote Ca exchangeability. This exchangeability is not influenced by caffeine, quinine, procaine, and tetracaine, and Ca that is either nonexchangeable (in the absence of ATP) or exchangeable (in the presence of ATP) is released by 1–5 mM quinine or tetracaine, but neither caffeine (6 mM) nor procaine (2–5 mM) has this effect. Quinine or tetracaine also releases Ca and Mg bound passively to the reticulum membranes. A possible role of ATP in maintaining the integrity of cellular membranes is discussed, and the effects of caffeine, quinine, and of local anesthetics on the binding of Ca by the isolated reticulum are related to the effects of these agents on 45Ca fluxes and on the twitch output observed in whole muscles. PMID:19873636

Assessing the permeability of the rat sciatic nerve epineural sheath against compounds with local anesthetic activity: an ex vivo electrophysiological study.

PubMed

Kagiava, Alexia; Theophilidis, George

2013-10-01

Abstract Studies have shown that the sciatic nerve epineural sheath acts as a barrier and has a delaying effect on the diffusion of local anesthetics into the nerve fibers and endoneurium. The purpose of this work is to assess and to quantify the permeability of the epineural sheath. For this purpose, we isolated the rat sciatic nerve in a three-chamber recording bath that allowed us to monitor the constant in amplitude evoked nerve compound action potential (nCAP) for over 24 h. For nerves exposed to the compounds under investigation, we estimated the IT50 the time required to inhibit the nCAP to 50% of its initial value. For desheathed nerves, the half-vitality time was denoted as IT50(-) and for the ensheath normal nerves as IT50(+). There was no significant difference between the IT50 of desheathed and ensheathed nerves exposed to normal saline. The IT50(-) for nerves exposed to 40 mM lidocaine was 12.1 ± 0.95 s (n=14) and the IT50(+) was 341.4 ± 2.49 s (n=6). The permeability (P) coefficient of the epineural sheath was defined as the ratio IT50(+)/IT50(-). The P coefficient for 40 mM lidocaine and linalool was 28.2 and 3.48, correspondingly, and for 30 mM 2-heptanone was 4.87. This is an indication that the epineural sheath provided a stronger barrier against lidocaine, compared to natural local anesthetics, linalool and 2-heptanone. The methodology presented here is a useful tool for studying epineural sheath permeability to compounds with local anesthetic properties.

The use of compound topical anesthetics: a review.

PubMed

Kravitz, Neal D

2007-10-01

The author reviewed the history of, federal regulations regarding, risks of and adverse drug reactions of five compound topical anesthetics: tetracaine, adrenaline/epinephrine and cocaine (TAC); lidocaine, adrenaline/epinephrine and tetracaine (LET); lidocaine, tetracaine and phenylephrine (TAC 20 percent Alternate); lidocaine, prilocaine and tetracaine (Profound); and lidocaine, prilocaine, tetracaine and phenylephrine with thickeners (Profound PET). The author reviewed clinical trials, case reports, descriptive articles, and U.S. Food and Drug Administration (FDA) regulations and recent public advisory warnings regarding the federal approval of and risks associated with the use of compound topical anesthetics. Compound topical anesthetics are neither FDA-regulated nor -unregulated. Some compounding pharmacies bypass the new FDA drug approval process, which is based on reliable scientific data and ensures that a marketed drug is safe, effective, properly manufactured and accurately labeled. Two deaths have been attributed to the lay use of compound topical anesthetics. In response, the FDA has announced the strengthening of its efforts against unapproved drug products. Compound topical anesthetics may be an effective alternative to local infiltration for some minimally invasive dental procedures; however, legitimate concerns exist in regard to their safety. Until they become federally regulated, compound topical anesthetics remain unapproved drug products whose benefits may not outweigh their risks for dental patients.

Modifying the baricity of local anesthetics for spinal anesthesia by temperature adjustment: model calculations.

PubMed

Heller, Axel R; Zimmermann, Katrin; Seele, Kristin; Rössel, Thomas; Koch, Thea; Litz, Rainer J

2006-08-01

Although local anesthetics (LAs) are hyperbaric at room temperature, density drops within minutes after administration into the subarachnoid space. LAs become hypobaric and therefore may cranially ascend during spinal anesthesia in an uncontrolled manner. The authors hypothesized that temperature and density of LA solutions have a nonlinear relation that may be described by a polynomial equation, and that conversion of this equation may provide the temperature at which individual LAs are isobaric. Density of cerebrospinal fluid was measured using a vibrating tube densitometer. Temperature-dependent density data were obtained from all LAs commonly used for spinal anesthesia, at least in triplicate at 5 degrees, 20 degrees, 30 degrees, and 37 degrees C. The hypothesis was tested by fitting the obtained data into polynomial mathematical models allowing calculations of substance-specific isobaric temperatures. Cerebrospinal fluid at 37 degrees C had a density of 1.000646 +/- 0.000086 g/ml. Three groups of local anesthetics with similar temperature (T, degrees C)-dependent density (rho) characteristics were identified: articaine and mepivacaine, rho1(T) = 1.008-5.36 E-06 T2 (heavy LAs, isobaric at body temperature); L-bupivacaine, rho2(T) = 1.007-5.46 E-06 T2 (intermediate LA, less hypobaric than saline); bupivacaine, ropivacaine, prilocaine, and lidocaine, rho3(T) = 1.0063-5.0 E-06 T (light LAs, more hypobaric than saline). Isobaric temperatures (degrees C) were as follows: 5 mg/ml bupivacaine, 35.1; 5 mg/ml L-bupivacaine, 37.0; 5 mg/ml ropivacaine, 35.1; 20 mg/ml articaine, 39.4. Sophisticated measurements and mathematic models now allow calculation of the ideal injection temperature of LAs and, thus, even better control of LA distribution within the cerebrospinal fluid. The given formulae allow the adaptation on subpopulations with varying cerebrospinal fluid density.

Local Anesthetic Peripheral Nerve Block Adjuvants for Prolongation of Analgesia: A Systematic Qualitative Review

PubMed Central

Kirksey, Meghan A.; Haskins, Stephen C.; Cheng, Jennifer; Liu, Spencer S.

2015-01-01

Background The use of peripheral nerve blocks for anesthesia and postoperative analgesia has increased significantly in recent years. Adjuvants are frequently added to local anesthetics to prolong analgesia following peripheral nerve blockade. Numerous randomized controlled trials and meta-analyses have examined the pros and cons of the use of various individual adjuvants. Objectives To systematically review adjuvant-related randomized controlled trials and meta-analyses and provide clinical recommendations for the use of adjuvants in peripheral nerve blocks. Methods Randomized controlled trials and meta-analyses that were published between 1990 and 2014 were included in the initial bibliographic search, which was conducted using Medline/PubMed, Cochrane Central Register of Controlled Trials, and EMBASE. Only studies that were published in English and listed block analgesic duration as an outcome were included. Trials that had already been published in the identified meta-analyses and included adjuvants not in widespread use and published without an Investigational New Drug application or equivalent status were excluded. Results Sixty one novel clinical trials and meta-analyses were identified and included in this review. The clinical trials reported analgesic duration data for the following adjuvants: buprenorphine (6), morphine (6), fentanyl (10), epinephrine (3), clonidine (7), dexmedetomidine (7), dexamethasone (7), tramadol (8), and magnesium (4). Studies of perineural buprenorphine, clonidine, dexamethasone, dexmedetomidine, and magnesium most consistently demonstrated prolongation of peripheral nerve blocks. Conclusions Buprenorphine, clonidine, dexamethasone, magnesium, and dexmedetomidine are promising agents for use in prolongation of local anesthetic peripheral nerve blocks, and further studies of safety and efficacy are merited. However, caution is recommended with use of any perineural adjuvant, as none have Food and Drug Administration approval, and

Interactions of anesthetics with the membrane-water interface

NASA Technical Reports Server (NTRS)

Pohorille, A.; Cieplak, P.; Wilson, M. A.

1996-01-01

Although the potency of conventional anesthetics correlates with lipophilicity, an affinity to water also is essential. It was recently found that compounds with very low affinities to water do not produce anesthesia regardless of their lipophilicity. This finding implies that clinical anesthesia might arise because of interactions at molecular sites near the interface of neuronal membranes with the aqueous environment and, therefore, might require increased concentrations of anesthetic molecules at membrane interfaces. As an initial test of this hypothesis, we calculated in molecular dynamics simulations the free energy profiles for the transfer of anesthetic 1,1,2-trifluoroethane and nonanesthetic perfluoroethane across water-membrane and water-hexane interfaces. Consistent with the hypothesis, it was found that trifluoroethane, but not perfluoroethane, exhibits a free energy minimum and, therefore, increased concentrations at both interfaces. The transfer of trifluoroethane from water to the nonpolar hexane or interior of the membrane is accompanied by a considerable, solvent-induced shift in the conformational equilibrium around the C-C bond.

Anesthetic effects on fictive locomotion in the rat isolated spinal cord

PubMed Central

Jinks, Steven L.; Andrada, Jason; Satter, Omar

2011-01-01

General anesthetic mechanisms are poorly understood. Anesthetic immobilizing effects occur in the spinal ventral horn. However, a detailed analysis of anesthetic effects on ventral motor networks is lacking. We delivered isoflurane, desflurane, or propofol during NMDA/5-HT-induced, or noxious tail stimulus-evoked, fictive locomotion in neonatal rat isolated spinal cords. Anesthetics changed the frequency, amplitude, and regularity of fictive locomotion with little effect on phase-lag. Isoflurane abolished pharmacologically-induced vs noxious stimulus-induced motor output at similar concentrations. Propofol abolished pharmacologically-induced fictive locomotion via a GABAA-receptor mechanism. Anesthetic effects on pharmacologically-elicted fictive locomotion appear clinically-relevant, and support a ventral horn immobilizing effect on locomotor rhythm generation. PMID:21817927

Refractometry for quality control of anesthetic drug mixtures.

PubMed

Stabenow, Jennifer M; Maske, Mindy L; Vogler, George A

2006-07-01

Injectable anesthetic drugs used in rodents are often mixed and further diluted to increase the convenience and accuracy of dosing. We evaluated clinical refractometry as a simple and rapid method of quality control and mixing error detection of rodent anesthetic or analgesic mixtures. Dilutions of ketamine, xylazine, acepromazine, and buprenorphine were prepared with reagent-grade water to produce at least 4 concentration levels. The refraction of each concentration then was measured with a clinical refractometer and plotted against the percentage of stock concentration. The resulting graphs were linear and could be used to determine the concentration of single-drug dilutions or to predict the refraction of drug mixtures. We conclude that refractometry can be used to assess the concentration of dilutions of single drugs and can verify the mixing accuracy of drug combinations when the components of the mixture are known and fall within the detection range of the instrument.

The effect of inhalant anesthetic and body temperature on peri-anesthetic serum concentrations of transdermally administered fentanyl in dogs.

PubMed

Pettifer, Glenn R; Hosgood, Giselle

2004-04-01

To determine whether moderate hypothermia during anesthesia significantly affects the serum concentration of transdermally delivered fentanyl and whether halothane or isoflurane affect these concentrations. Randomized cross-over experimental trial. Six mature, healthy Beagles (three males, three females) weighing 10.6 +/- 0.43 kg. A 50-microg hour(-1) fentanyl patch was applied 36 hours prior to anesthesia. Anesthesia was induced at time 0 (t = 0). Each dog received four treatments: isoflurane + normothermia (ISO-NORM), isoflurane + hypothermia (ISO-HYPO), halothane + normothermia (HAL-NORM), and halothane + hypothermia (HAL-HYPO). Dogs were intubated and maintained at 1.5 times MAC. Animals in the hypothermia treatments were cooled to 35 degrees C during anesthesia. Serum fentanyl analysis was performed at -36, -24, -12, 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 9, 10, 18, and 26 hours. Direct arterial blood pressures and arterial blood gases were monitored. The mean body temperatures (+/-SEM) during the anesthetic period for the four treatments were: ISO-NORM = 37.7 +/- 0.07 degrees C, ISO-HYPO = 35.8 +/- 0.1 degrees C, HAL-NORM = 37.7 +/- 0.06 degrees C, and HAL-HYPO = 35.8 +/- 0.13 degrees C. The mean (+/-SEM) serum fentanyl concentrations (SFC) for both hypothermia treatments were significantly lower than baseline concentrations at t = 1 hour and persisted for the duration of anesthesia for the ISO-HYPO treatment but only from t = 1 to 2 hours for the HAL-HYPO treatment. Serum fentanyl concentrations returned to baseline within one hour of the end of anesthesia, regardless of body temperature. There were no significant differences between treatments for systolic or diastolic blood pressure but mean blood pressures were higher during normothermia versus hypothermia during the last hour of anesthesia. Hypothermia during inhalation anesthesia produced a significant reduction in SFC using transdermal administration and was more protracted with isoflurane

Volatile Anesthetics Improve Survival after Cecal Ligation and Puncture

PubMed Central

Herrmann, Inge K.; Castellon, Maricela; Schwartz, David E.; Hasler, Melanie; Urner, Martin; Hu, Guochang; Minshall, Richard D.; Beck-Schimmer, Beatrice

2016-01-01

Background Sepsis remains a leading cause of death in intensive care units. There is growing evidence that volatile anesthetics have beneficial immunomodulatory effects on complex inflammation-mediated conditions. The authors investigated the effect of volatile anesthetics on the overall survival of mice in a sepsis model of cecal ligation and puncture (CLP). Methods Mice (N = 12 per treatment group) were exposed to anesthetic concentrations of desflurane, isoflurane, and sevoflurane either during induction of sepsis or when the mice showed pronounced symptoms of inflammation. Overall survival, as well as organ function and inflammation was compared with the CLP group without intervention. Results With desflurane and sevoflurane conditioning (1.2 minimal alveolar concentration for 2 h immediately after induction of CLP) overall survival was improved to 58% and 83%, respectively, compared with 17% in the untreated CLP group. Isoflurane did not significantly affect outcome. Application of sevoflurane 24 h after sepsis induction significantly improved overall survival to 66%. Conclusions Administration of the volatile anesthetics desflurane and sevoflurane reduced CLP-induced mortality. Anesthesia may be a critical confounder when comparing study data where different anesthesia protocols were used. PMID:23867232

Continuous intra-articular local anesthetic drug instillation versus discontinuous sciatic nerve block after total knee arthroplasty.

PubMed

Cip, Johannes; Erb-Linzmeier, Hedwig; Stadlbauer, Peter; Bach, Christian; Martin, Arno; Germann, Reinhard

2016-12-01

Sciatic nerve block (SNB) is commonly used as adjunct to femoralis nerve block (FNB) to achieve high-quality pain relief after total knee arthroplasty (TKA). However, this combination is associated with considerable muscle weakness, foot drop and surgically related nerve injuries may be masked. The purpose of this study was to assess whether low risk continuous intra-articular anesthetic drug instillation is an adequate alternative to SNB when adding to FNB after TKA. Retrospective investigational follow-up study. University teaching hospital. Interdisciplinary postoperative anesthetic and orthopedic survey. For this investigational analysis, 34 of 50 consecutive patients were available. All patients underwent primary unilateral TKA. Group A (18 patients) received a continuous intra-articular 0.33% ropivacaine (5 mL/h) instillation for the first 48 h postoperatively. In Group B (16 patients) a discontinuous SNB was used. Both groups were treated with a continuous FNB. Main endpoints were mean and maximum postoperative pain intensity levels for both anterior and posterior knee side, amount of postoperative administered opioid drugs, differences in functional outcome or hospital stay and rate of postoperative complications. Group A showed higher pain intensity levels for the posterior knee side (P≤.042). Merely on the second postoperative day there were no differences within either study group. No differences were found regarding anterior knee pain. Group A showed a significant higher postoperative piritramid consumption (P≤.007). Length of hospital stay or postoperative functional outcome was not significant different. Postoperative complications were not related to anesthesia techniques. SNB technique resulted in superior pain relief in comparison to continuous intra-articular local anesthetic drug instillation as adjunct to continuous FNB after TKA. Copyright © 2016 Elsevier Inc. All rights reserved.

Anesthetic Agent-Specific Effects on Synaptic Inhibition

PubMed Central

MacIver, M. Bruce

2014-01-01

Background Anesthetics enhance gamma-aminobutyric acid (GABA)-mediated inhibition in the central nervous system. Different agents have been shown to act on tonic versus synaptic GABA receptors to different degrees, but it remains unknown whether different forms of synaptic inhibition are also differentially engaged. With this in mind, we tested the hypothesis that different types of GABA-mediated synapses exhibit different anesthetic sensitivities. The present study compared effects produced by isoflurane, halothane, pentobarbital, thiopental and propofol on paired pulse GABAA receptor-mediated synaptic inhibition. Effects on glutamate-mediated facilitation were also studied. Methods Synaptic responses were measured in rat hippocampal brain slices. Orthodromic paired pulse stimulation was used to assess anesthetic effects on either glutamate-mediated excitatory inputs or GABA-mediated inhibitory inputs to CA1 neurons. Antidromic stimulation was used to assess anesthetic effects on CA1 background excitability. Agents were studied at equi-effective concentrations for population spike depression to compare their relative degree of effect on synaptic inhibition. Results Differing degrees of anesthetic effect on paired pulse facilitation at excitatory glutamate synapses were evident, and blocking GABA inhibition revealed a previously unseen presynaptic action for pentobarbital. Although all five anesthetics depressed synaptically evoked excitation of CA1 neurons, the involvement of enhanced GABA-mediated inhibition differed considerably among agents. Single pulse inhibition was enhanced by propofol, thiopental and pentobarbital, but only marginally by halothane and isoflurane. In contrast, isoflurane enhanced paired pulse inhibition strongly, as did thiopental, but propofol, pentobarbital and halothane were less effective. Conclusions These observations support the idea that different GABA synapses use receptors with differing subunit compositions, and that anesthetics

Anesthesia with Isoflurane and Sevoflurane in the Crested Serpent Eagle (Spilornis cheela hoya): Minimum Anesthetic Concentration, Physiological Effects, Hematocrit, Plasma Chemistry and Behavioral Effects

PubMed Central

CHAN, Fang-Tse; CHANG, Geng-Ruei; WANG, Hsien-Chi; HSU, Tien-Huan

2013-01-01

ABSTRACT The initial goal of this study was to determine the minimum anesthetic concentration (MAC) for isoflurane (ISO) and sevoflurane (SEVO) for the crested serpent eagle. Next, we compared the anesthetic effects of each on the physiological effects, hematocrit, plasma chemistry values and behavior in spontaneously breathing captive adult crested serpent eagles. Sixteen eagles were randomly allocated to two groups for anesthesia with ISO (n=8) or SEVO (n=8). First, we measured the MAC values of ISO and SEVO, and four weeks later, we investigated the effect of each on the physiological effects, hematocrit (HCT) and plasma chemistry values. The MAC values of ISO and SEVO for crested serpent eagles were 1.46 ± 0.30 and 2.03 ± 0.32%, respectively. The results revealed no significant differences between the two anesthetics in induction time, while time of extubation to recovery was significantly shorter with SEVO. A time-related increase in end-tidal CO2 and decreases in body temperature and respiratory rates were observed during anesthesia with each anesthetic. There were no significant differences between the effect of the two anesthetics on heart rate, hematocrit, plasma chemistry values or respiration, although each caused minor respiration depression. We concluded that SEVO is a more effective inhalant agent than ISO for use in eagles, showing the most rapidest induction and recovery from anesthesia. PMID:23955396

Anesthesia with isoflurane and sevoflurane in the crested serpent eagle (Spilornis cheela hoya): minimum anesthetic concentration, physiological effects, hematocrit, plasma chemistry and behavioral effects.

PubMed

Chan, Fang-Tse; Chang, Geng-Ruei; Wang, Hsien-Chi; Hsu, Tien-Huan

2013-12-30

The initial goal of this study was to determine the minimum anesthetic concentration (MAC) for isoflurane (ISO) and sevoflurane (SEVO) for the crested serpent eagle. Next, we compared the anesthetic effects of each on the physiological effects, hematocrit, plasma chemistry values and behavior in spontaneously breathing captive adult crested serpent eagles. Sixteen eagles were randomly allocated to two groups for anesthesia with ISO (n=8) or SEVO (n=8). First, we measured the MAC values of ISO and SEVO, and four weeks later, we investigated the effect of each on the physiological effects, hematocrit (HCT) and plasma chemistry values. The MAC values of ISO and SEVO for crested serpent eagles were 1.46 ± 0.30 and 2.03 ± 0.32%, respectively. The results revealed no significant differences between the two anesthetics in induction time, while time of extubation to recovery was significantly shorter with SEVO. A time-related increase in end-tidal CO₂ and decreases in body temperature and respiratory rates were observed during anesthesia with each anesthetic. There were no significant differences between the effect of the two anesthetics on heart rate, hematocrit, plasma chemistry values or respiration, although each caused minor respiration depression. We concluded that SEVO is a more effective inhalant agent than ISO for use in eagles, showing the most rapidest induction and recovery from anesthesia.

Awake vs. anesthetized: layer-specific sensory processing in visual cortex and functional connectivity between cortical areas

PubMed Central

Sellers, Kristin K.; Bennett, Davis V.; Hutt, Axel; Williams, James H.

2015-01-01

During general anesthesia, global brain activity and behavioral state are profoundly altered. Yet it remains mostly unknown how anesthetics alter sensory processing across cortical layers and modulate functional cortico-cortical connectivity. To address this gap in knowledge of the micro- and mesoscale effects of anesthetics on sensory processing in the cortical microcircuit, we recorded multiunit activity and local field potential in awake and anesthetized ferrets (Mustela putoris furo) during sensory stimulation. To understand how anesthetics alter sensory processing in a primary sensory area and the representation of sensory input in higher-order association areas, we studied the local sensory responses and long-range functional connectivity of primary visual cortex (V1) and prefrontal cortex (PFC). Isoflurane combined with xylazine provided general anesthesia for all anesthetized recordings. We found that anesthetics altered the duration of sensory-evoked responses, disrupted the response dynamics across cortical layers, suppressed both multimodal interactions in V1 and sensory responses in PFC, and reduced functional cortico-cortical connectivity between V1 and PFC. Together, the present findings demonstrate altered sensory responses and impaired functional network connectivity during anesthesia at the level of multiunit activity and local field potential across cortical layers. PMID:25833839

Anesthetics mechanism on a DMPC lipid membrane model: Insights from molecular dynamics simulations.

PubMed

Saeedi, Marzieh; Lyubartsev, Alexander P; Jalili, Seifollah

2017-07-01

To provide insight into the molecular mechanisms of local anesthetic action, we have carried out an extensive investigation of two amide type local anesthetics, lidocaine and articaine in both charged and uncharged forms, interacting with DMPC lipid membrane. We have applied both standard molecular dynamics simulations and metadynamics simulations to provide a detailed description of the free energy landscape of anesthetics embedded in the lipid bilayer. The global minimum of the free energy surface (equilibrium position of anesthetics in the lipid membrane) occurred around 1nm of the bilayer center. The uncharged anesthetics show more affinity to bind to this region compared to the charged drugs. The binding free energy of uncharged lidocaine in the membrane (-30.3kJ/mol) is higher than uncharged articaine (-24.0kJ/mol), which is in good agreement with higher lipid solubility of lidocaine relative to the articaine. The octanol/water partition coefficient of uncharged drugs was also investigated using expanded ensemble simulations. In addition, complementary standard MD simulations were carried out to study the partitioning behavior of multiple anesthetics inside the lipid bilayer. The results obtained here are in line with previously reported simulations and suggest that the different forms of anesthetics induce different structural modifications in the lipid bilayer, which can provide new insights into their complex membrane translocation phenomena. Copyright © 2017 Elsevier B.V. All rights reserved.

Analgesic efficacy of ultrasound guided transversus abdominis plane block versus local anesthetic infiltration in adult patients undergoing single incision laparoscopic cholecystectomy: A randomized controlled trial.

PubMed

Bava, Ejas P; Ramachandran, Rashmi; Rewari, Vimi; Chandralekha; Bansal, Virinder Kumar; Trikha, Anjan

2016-01-01

Transversus abdominis plane (TAP) block has been used to provide intra- and post-operative analgesia with single incision laparoscopic (SIL) bariatric and gynecological surgery with mixed results. Its efficacy in providing analgesia for SIL cholecystectomy (SILC) via the same approach remains unexplored. The primary objective of our study was to compare the efficacy of bilateral TAP block with local anesthetic infiltration for perioperative analgesia in patients undergoing SILC. This was a prospective, randomized, controlled, double-blinded trial performed in a tertiary care hospital. Forty-two patients undergoing SILC were randomized to receive either ultrasound-guided (USG) bilateral mid-axillary TAP blocks with 0.375% ropivacaine or local anesthetic infiltration of the port site. The primary outcome measure was the requirement of morphine in the first 24 h postoperatively. The data were analyzed using t -test, Mann-Whitney test or Chi-square test. The 24 h morphine requirement (mean ± standard deviation) was 34.57 ± 14.64 mg in TAP group and 32.76 ± 14.34 mg in local infiltration group ( P = 0.688). The number of patients requiring intraoperative supplemental fentanyl in TAP group was 8 and in local infiltration group was 16 ( P = 0.028). The visual analog scale scores at rest and on coughing were significantly higher in the local infiltration group in the immediate postoperative period ( P = 0.034 and P = 0.007, respectively). USG bilateral TAP blocks were not effective in decreasing 24 h morphine requirement as compared to local anesthetic infiltration in patients undergoing SILC although it provided some analgesic benefit intraoperatively and in the initial 4 h postoperatively. Hence, the benefits of TAP blocks are not worth the effort and time spent for administering them for this surgery.

Analgesic efficacy of ultrasound guided transversus abdominis plane block versus local anesthetic infiltration in adult patients undergoing single incision laparoscopic cholecystectomy: A randomized controlled trial

PubMed Central

Bava, Ejas P.; Ramachandran, Rashmi; Rewari, Vimi; Chandralekha; Bansal, Virinder Kumar; Trikha, Anjan

2016-01-01

Background: Transversus abdominis plane (TAP) block has been used to provide intra- and post-operative analgesia with single incision laparoscopic (SIL) bariatric and gynecological surgery with mixed results. Its efficacy in providing analgesia for SIL cholecystectomy (SILC) via the same approach remains unexplored. Aims: The primary objective of our study was to compare the efficacy of bilateral TAP block with local anesthetic infiltration for perioperative analgesia in patients undergoing SILC. Settings and Design: This was a prospective, randomized, controlled, double-blinded trial performed in a tertiary care hospital. Materials and Methods: Forty-two patients undergoing SILC were randomized to receive either ultrasound-guided (USG) bilateral mid-axillary TAP blocks with 0.375% ropivacaine or local anesthetic infiltration of the port site. The primary outcome measure was the requirement of morphine in the first 24 h postoperatively. Statistical Analysis: The data were analyzed using t-test, Mann–Whitney test or Chi-square test. Results: The 24 h morphine requirement (mean ± standard deviation) was 34.57 ± 14.64 mg in TAP group and 32.76 ± 14.34 mg in local infiltration group (P = 0.688). The number of patients requiring intraoperative supplemental fentanyl in TAP group was 8 and in local infiltration group was 16 (P = 0.028). The visual analog scale scores at rest and on coughing were significantly higher in the local infiltration group in the immediate postoperative period (P = 0.034 and P = 0.007, respectively). Conclusion: USG bilateral TAP blocks were not effective in decreasing 24 h morphine requirement as compared to local anesthetic infiltration in patients undergoing SILC although it provided some analgesic benefit intraoperatively and in the initial 4 h postoperatively. Hence, the benefits of TAP blocks are not worth the effort and time spent for administering them for this surgery. PMID:27746552

Antimicrobial Properties of Topical Anesthetic Liquids Containing Lidocaine or Benzocaine

PubMed Central

Morrow, Mark E.; Berry, Charles W.

1988-01-01

Six species of microorganisms commonly found within the oral cavity were exposed for either one minute or two hours to 5% lidocaine liquid topical anesthetic and benzocaine liquid topical anesthetic. Mixtures of microorganisms and anesthetics were diluted and plated onto a brain heart infusion medium. Reduction in cell viability was 73-100% after exposure to the anesthetic agents when compared with the saline/buffer controls. A significant reduction (p < .005) in cell growth by Streptococcus mutans, S. sanguis, S. mitis, S. salivarius, Actinomyces viscosus, and Candida albicans was associated with a one-minute and two-hour exposure to lidocaine, benzocaine, 5% lidocaine, and the benzocaine vehicle control. Five percent lidocaine reduced growth of the test orgainisms more than benzocaine in one-minute exposures to S. mutans, A. viscosus and S. salivarius and with a two-hour exposure to S. salivarius. Five percent lidocaine was bacteriocidal or fungicidal to all microorganisms for both time periods whereas, benzocaine liquid topical anesthetic was predominately bacteriostatic or fungistatic after one-minute exposures and bacteriocidal or fungicidal after two hours. The results indicated that two dental liquid topical anesthetics containing lidocaine or benzocaine possessed considerable antimicrobial activity to selected oral microorganisms. The exclusive use of a topical liquid anesthetic may be an adequate means to render the oral mucosa aseptic before injection of a local anesthetic. PMID:3278655

Pharmacoeconomics of inhaled anesthetic agents: considerations for the pharmacist.

PubMed

Chernin, Eric L

2004-10-15

Types of economic analyses used for inhaled anesthetic agents, factors to consider in calculating the cost of inhaled anesthetics, limitations of pharmacoeconomic studies of these agents, and strategies for controlling inhaled anesthetic costs are discussed. Inhaled anesthetic agents comprise a substantial component of drug budgets. Calculation of the cost of administering an inhaled anesthetic should take into consideration the cost per mL, potency, waste, concentration and duration of gas delivery, fresh gas flow rate, molecular weight, and density. The use of newer inhaled anesthetic agents with low solubility in blood and tissue provides a more rapid recovery from anesthesia than older, more soluble agents, and also provides the same level of control of depth of anesthesia at a lower fresh gas flow rate and possibly a lower cost than older agents at a higher fresh gas flow rate. A more rapid recovery may facilitate fast-track recovery and yield cost savings if it allows the completion of additional surgical cases or allows a reduction in personnel overtime expenses. Interpretation of pharmacoeconomic studies of inhaled anesthetics requires an appreciation of the limitations in methodology and ability to extrapolate results from one setting to another. Pharmacists' efforts to reduce anesthetic waste and collaborate with anesthesiologists to improve the use of these agents can help contain costs, but improving scheduling and efficiency in the operating room has a greater potential to reduce operating room costs. Much can be done to control costs of anesthetic agents without compromising availability of these agents and patient care.

Rapid Vortex Fluidics: Continuous Flow Synthesis of Amides and Local Anesthetic Lidocaine.

PubMed

Britton, Joshua; Chalker, Justin M; Raston, Colin L

2015-07-20

Thin film flow chemistry using a vortex fluidic device (VFD) is effective in the scalable acylation of amines under shear, with the yields of the amides dramatically enhanced relative to traditional batch techniques. The optimized monophasic flow conditions are effective in ≤80 seconds at room temperature, enabling access to structurally diverse amides, functionalized amino acids and substituted ureas on multigram scales. Amide synthesis under flow was also extended to a total synthesis of local anesthetic lidocaine, with sequential reactions carried out in two serially linked VFD units. The synthesis could also be executed in a single VFD, in which the tandem reactions involve reagent delivery at different positions along the rapidly rotating tube with in situ solvent replacement, as a molecular assembly line process. This further highlights the versatility of the VFD in organic synthesis, as does the finding of a remarkably efficient debenzylation of p-methoxybenzyl amines. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Postoperative environmental anesthetic vapour concentrations following removal of the airway device in the operating room versus the postanesthesia care unit.

PubMed

Cheung, Sara K; Özelsel, Timur; Rashiq, Saifee; Tsui, Ban C

2016-09-01

This study was designed to compare waste anesthetic gas (WAG) concentrations within patients' breathing zones after removal of the patient's airway device in the postanesthesia care unit (PACU) vs in the operating room (OR). Following Research Ethics Board approval and patient consent, we recruited patients undergoing surgery who received volatile anesthesia via an endotracheal tube or supraglottic airway. Patients had their airway device removed in the OR or in the PACU depending on the attending anesthesiologist's preference. Upon the patient's arrival in the PACU, concentrations of exhaled sevoflurane and desflurane were measured at their breathing zone (i.e., 15 cm from the patient's mouth and nose) using a single-beam infrared spectrophotometer. Seventy patients were recruited during the five-month study period. The median [interquartile range] WAG levels in the patients' breathing zones were higher when their airway devices were removed in the PACU vs in the OR. The WAG levels for sevoflurane were 0.7 [0.4-1.1] parts per million (ppm) vs 0.5 [0.4-0.7] ppm, respectively; median difference, 0.3; 95% confidence interval (CI), 0.1 to 0.6; P = 0.04. The WAG levels for desflurane were 2.4 [1.2-3.4] ppm vs 4.1 [2.5-5.2] ppm, respectively; median difference, 1.5; 95% CI, 0.3 to 2.7; P = 0.04. After a volatile-based anesthetic, our results suggest that removal of the airway device in the PACU vs in the OR increases the amount of waste anesthetic gas in a patient's breathing zone and thus potentially in the PACU nurse's working zone.

Validation of the bispectral index as an indicator of anesthetic depth in Thoroughbred horses anesthetized with sevoflurane

PubMed Central

TOKUSHIGE, Hirotaka; KAKIZAKI, Masashi; ODE, Hirotaka; OKANO, Atsushi; OKADA, Jun; KURODA, Taisuke; WAKUNO, Ai; OHTA, Minoru

2016-01-01

ABSTRACT To evaluate the bispectral index (BIS) as an indicator of anesthetic depth in Thoroughbred horses, BIS values were measured at multiple stages of sevoflurane anesthesia in five horses anesthetized with guaifenesin and thiopental following premedication with xylazine. There was no significant difference between the BIS values recorded at end-tidal sevoflurane concentrations of 2.8% (median 60 ranging from 47 to 68) and 3.5% (median 71 ranging from 49 to 82) in anesthetized horses. These BIS values during anesthesia were significantly lower (P<0.01) than those in awake horses (median 98 ranging from 98 to 98) or sedated horses (median 92 ranging from 80 to 93). During the recovery phase, the BIS values gradually increased over time but did not significantly increase until the horses showed movement. In conclusion, the BIS value could be useful as an indicator of awakening during the recovery period in horses, as previous reported. PMID:27974877

The immune response to anesthesia: part 2 sedatives, opioids, and injectable anesthetic agents.

PubMed

Anderson, Stacy L; Duke-Novakovski, Tanya; Singh, Baljit

2014-11-01

To review the immune response to injectable anesthetics and sedatives and to compare the immunomodulatory properties between inhalation and injectable anesthetic protocols. Review. Multiple literature searches were performed using PubMed and Google Scholar from March 2012 through November 2013. Relevant anesthetic and immune terms were used to search databases without year published or species constraints. The online database for Veterinary Anaesthesia and Analgesia and the Journal of Veterinary Emergency and Critical Care were searched by issue starting in 2000 for relevant articles. Sedatives, injectable anesthetics, opioids, and local anesthetics have immunomodulatory effects that may have positive or negative consequences on disease processes such as endotoxemia, generalized sepsis, tumor growth and metastasis, and ischemia-reperfusion injury. Therefore, anesthetists should consider the immunomodulatory effects of anesthetic drugs when designing anesthetic protocols for their patients. © 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

Local anesthetic delivery via surgical drain provides improved pain control versus direct skin infiltration following axillary node dissection for breast cancer.

PubMed

Khpal, Muska; Miller, James R C; Petrovic, Zika; Hassanally, Delilah

2018-03-01

Axillary node dissection has a central role in the surgical management of breast cancer; however, it is associated with a significant risk of lymphoedema and chronic pain. Peri-operative administration of local anesthesia reduces acute and persistent post-surgical pain, but there is currently no consensus on the optimal method of local anesthetic delivery. Patients undergoing axillary dissection for breast cancer were randomly assigned to receive a one-off dose of levobupivacaine 0.5% (up to 2 mg/kg) following surgery, either via the surgical drain or by direct skin infiltration. Post-operative pain control at rest and on shoulder abduction was assessed using a numerical rating scale. Total analgesia consumption 48 h after surgery was also recorded. Pain scores were significantly lower when local anesthesia was administered via surgical drain at both 3 and 12 h after surgery; this trend extended to 24 h post-operatively. However, pain scores on shoulder abduction did not differ at the 12 or 24 h time points. No differences were found in the total analgesia consumption or length of hospital stay between treatment groups. This study demonstrates that local anesthetic delivery via a surgical drain provides improved pain control compared to direct skin infiltration following axillary node dissection. This is likely to be important for the management of acute pain in the immediate post-operative period; however, further studies may be required to validate this in specific patient subgroups, e.g., breast-conserving surgery versus mastectomy.

The pH-dependent local anesthetic activity of diethylaminoethanol, a procaine metabolite.

PubMed

Butterworth, J F; Lief, P A; Strichartz, G R

1988-04-01

To test whether the products of procaine hydrolysis have local anesthetic actions resembling those of procaine, the authors compared the ability of procaine and its metabolites diethylaminoethanol (DEAE) and para-aminobenzoic acid (PABA) to block compound action potentials in excised, desheathed frog and rat sciatic nerves. Studies were performed in solutions of impermeant buffers at pH 7.4 (corresponding to mammalian physiologic pH) and at pH 9.2 (close to the pKa of procaine and DEAE) to test for extracellular pH-dependent increases in drug permeation and potency. Both procaine and DEAE inhibited compound action potentials at pH 7.4 and 9.2 in a reversible and dose-dependent manner, and both were approximately ten-fold more potent at pH 9.2 than at pH 7.4, procaine inhibiting the action potential height by 50% at 0.15 mM (pH 9.2) and 1.1 mM (pH 7.4), DEAE at 4 mM (pH 9.2) and 70 mM (pH 7.4). In contrast, PABA at concentrations up to 25 mM and at either pH failed to inhibit compound action potentials, and did not modify the effects of DEAE when both drugs were given together. Procaine produced greater use-dependent block at the higher pH and at higher stimulation rates (100 Hz vs. 40 Hz); DEAE produced almost no use-dependent block. These observations suggest: 1) that DEAE might account for some of the neuropharmacologic activity of procaine in techniques that favor the accumulation of metabolites (such as those requiring large doses or prolonged infusions); and 2) that alkalinization of procaine and DEAE solutions appears to increase their potency for both resting and use-dependent block of action potentials.

Local anesthetic inhibition of a bacterial sodium channel

PubMed Central

Lee, Sora; Goodchild, Samuel J.

2012-01-01

Recent structural breakthroughs with the voltage-gated sodium channel from Arcobacter butzleri suggest that such bacterial channels may provide a structural platform to advance the understanding of eukaryotic sodium channel gating and pharmacology. We therefore set out to determine whether compounds known to interact with eukaryotic NaVs could also inhibit the bacterial channel from Bacillus halodurans and NaChBac and whether they did so through similar mechanisms as in their eukaryotic homologues. The data show that the archetypal local anesthetic (LA) lidocaine inhibits resting NaChBac channels with a dissociation constant (Kd) of 260 µM, and channels displayed a left-shifted steady-state inactivation gating relationship in the presence of the drug. Extracellular application of QX-314 to expressed NaChBac channels had no effect on sodium current, whereas internal exposure via injection of a bolus of the quaternary derivative rapidly reduced sodium conductance, consistent with a hydrophilic cytoplasmic access pathway to an internal binding site. However, the neutral derivative benzocaine applied externally inhibited NaChBac channels, suggesting that hydrophobic pathways can also provide drug access to inhibit channels. Alternatively, ranolazine, a putative preopen state blocker of eukaryotic NaVs, displayed a Kd of 60 µM and left-shifted the NaChBac activation-voltage relationship. In each case, block enhanced entry into the inactivated state of the channel, an effect that is well described by a simple kinetic scheme. The data suggest that although significant differences exist, LA block of eukaryotic NaVs also occurs in bacterial sodium channels and that NaChBac shares pharmacological homology to the resting state of vertebrate NaV homologues. PMID:22641643

n-Dodecyl β-D-maltoside specifically competes with general anesthetics for anesthetic binding sites.

PubMed

Xu, Longhe; Matsunaga, Felipe; Xi, Jin; Li, Min; Ma, Jingyuan; Liu, Renyu

2014-01-01

We recently demonstrated that the anionic detergent sodium dodecyl sulfate (SDS) specifically interacts with the anesthetic binding site in horse spleen apoferritin, a soluble protein which models anesthetic binding sites in receptors. This raises the possibility of other detergents similarly interacting with and occluding such sites from anesthetics, thereby preventing the proper identification of novel anesthetic binding sites. n-Dodecyl β-D-maltoside (DDM) is a non-ionic detergent commonly used during protein-anesthetic studies because of its mild and non-denaturing properties. In this study, we demonstrate that SDS and DDM occupy anesthetic binding sites in the model proteins human serum albumin (HSA) and horse spleen apoferritin and thereby inhibit the binding of the general anesthetics propofol and isoflurane. DDM specifically interacts with HSA (Kd = 40 μM) with a lower affinity than SDS (Kd = 2 μM). DDM exerts all these effects while not perturbing the native structures of either model protein. Computational calculations corroborated the experimental results by demonstrating that the binding sites for DDM and both anesthetics on the model proteins overlapped. Collectively, our results indicate that DDM and SDS specifically interact with anesthetic binding sites and may thus prevent the identification of novel anesthetic sites. Special precaution should be taken when undertaking and interpreting results from protein-anesthetic investigations utilizing detergents like SDS and DDM.

Comparison of subarachnoid anesthetic effect of emulsified volatile anesthetics in rats.

PubMed

Guo, Jiao; Zhou, Cheng; Liang, Peng; Huang, Han; Li, Fengshan; Chen, Xiangdong; Liu, Jin

2014-01-01

Spinal cord is an important target of volatile anesthetics in particular for the effect of immobility. Intrathecal injection of volatile anesthetics has been found to produce subarachnoid anesthesia. The present study was designed to compare spinal anesthetic effects of emulsified volatile anesthetics, and to investigate the correlation between their spinal effects and general effect of immobility. In this study, halothane, isoflurane, enflurane and sevoflurane were emulsified by 30% Intralipid. These emulsified volatile anesthetics were intravenously and intrathecally injected, respectively. ED50 of general anesthesia and EC50 of spinal anesthesia were determined. The durations of general and spinal anesthesia were recorded. Correlation analysis was applied to evaluate the anesthetic potency of volatile anesthetics between their spinal and general effects. ED50 of general anesthesia induced by emulsified halothane, isoflurane, enflurane and sevoflurane were 0.41 ± 0.07, 0.54 ± 0.07, 0.74 ± 0.11 and 0.78 ± 0.08 mmol/kg, respectively, with significant correlation to their inhaled MAC (R(2) = 0.8620, P = 0.047). For intrathecal injection, EC50 of spinal anesthesia induced by emulsified halothane, isoflurane, enflurane and sevoflurane were 0.35, 0.27, 0.33 and 0.26 mol/L, respectively, which could be predicted by the product of inhaled MAC and olive oil/gas partition coefficients (R(2) = 0.9627, P = 0.013). In conclusion, potency and efficacy of the four emulsified volatile anesthetics in spinal anesthesia were similar and could be predicted by the product of inhaled MAC and olive oil/gas partition coefficients (MAC × olive oil/gas partition coefficients).

Local anesthetic wound infiltration for pain management after periacetabular osteotomy. A randomized, placebo-controlled, double-blind clinical trial with 53 patients.

PubMed

Bech, Rune D; Ovesen, Ole; Lindholm, Peter; Overgaard, Søren

2014-04-01

To our knowledge, there is no evidence to support the use of local infiltration analgesia (LIA) for postoperative pain relief after periacetabular osteotomy (PAO). We investigated the effect of wound infiltration with a long-acting local anesthetic (ropivacaine) for postoperative analgesia after PAO. We performed a randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov: NCT00815503) in 53 patients undergoing PAO to evaluate the effect of local anesthetic infiltration on postoperative pain and on postoperative opioid consumption. All subjects received intraoperative infiltration followed by 5 postoperative injections in 10-hour intervals through a multi-holed catheter placed at the surgical site. 26 patients received ropivacaine and 27 received saline. The intervention period was 2 days and the observational period was 4 days. All subjects received patient-controlled opioid analgesia without any restrictions on the total daily dose. Pain was assessed at specific postoperative time points and the daily opioid usage was registered. Infiltration with 75 mL (150 mg) of ropivacaine did not reduce postoperative pain or opioid requirements during the first 4 days. The clinical importance of ropivacaine as single component in postoperative treatment of pain is questionable, and we are planning further studies to explore the potential of LIA in larger volume-and also a multimodal regimen-to treat pain in this category of patients.

Anesthetic activity of plant essential oils on Cyprinus carpio (koi carp).

PubMed

Khumpirapang, Nattakanwadee; Pikulkaew, Surachai; Anuchapreeda, Songyot; Okonogi, Siriporn

2018-03-19

The aims of this study were to investigate the anesthetic and cytotoxic effects of essential oils (EOs) of Ocimum basilicum (OBO), O. canum (OCO), and O. sanctum (OSO) on Cyprinus carpio (koi carp). For anesthetic effect, induction time to surgical anesthesia and recovery time were determined. For cytotoxicity effect, viability of fish peripheral blood nuclear cells (PBMCs) was investigated. Results indicated that increasing oil concentration caused significant (p < 0.01) decrease of induction time. OSO at 100, 200, and 300 mg/L gave the induction time of 169.5 ± 10.2, 62.8 ± 2.3, 45.3 ± 2.2 sec, respectively, significantly shorter than OCO, and OBO. The recovery time of anesthetized fish was dose dependent (p <0.01). Among them, OCO showed the longest recovery time of 313.0 ± 8.1, 420.7 ± 12.6, 616.6 ± 12.1 sec for concentrations of 100, 200, and 300 mg/L, respectively, followed by OSO and OBO, respectively. Within 10 min contact time of the EOs and fish PBMCs, the fish PBMC viability was higher than 80%. Increase contact time and EO concentration caused an increase in cytotoxicity to fish PBMC. OBO showed less toxic than OSO and OCO. Based on the desired induction and recovery times for anesthetizing koi carp, OBO, OCO, and OSO at 300, 200, and 100 mg/L, respectively were suggested to be the most suitable. It was concluded that OBO, OCO, and OSO can be used as natural anesthetics for fish.

Anesthetic depth and long-term survival: an update.

PubMed

Leslie, Kate; Short, Timothy G

2016-02-01

The purpose of this paper is to review the current evidence relating anesthetic depth to long-term survival after surgery. Using PubMed as the principal source, this review included published studies in all languages comparing mortality in patients with low- and high-processed electro-encephalo-graphic index values. All published studies used the bispectral index (BIS) monitor to measure anesthetic depth. The majority of the published observational studies were post hoc analyses of studies undertaken for other purposes. Most of these studies report a statistically significant association between deep general anesthesia (i.e., BIS values < 45) and death. Some studies also suggest an association between deep general anesthesia and myocardial infarction or postoperative cognitive decline. The combination of low BIS values and low delivered anesthetic concentrations (thus defining increased anesthetic sensitivity) may identify patients at particularly high risk. One of the three available randomized controlled trials reports worse outcomes in the BIS = 50 group compared with the BIS > 80 group, and two report no difference in mortality between the BIS = 35 and BIS = 50-55 groups. The available evidence on anesthetic depth and long-term survival is inconclusive. Randomized controlled trials with carefully controlled arterial blood pressure are required.

When pharmacologic anesthesia is precluded: the value of hypnosis as a sole anesthetic agent in dentistry.

PubMed

Kleinhauz, M; Eli, I

1993-01-01

Occasionally, a dental patient presents his/her dentist with a history of hypersensitivity to local anesthetic agents. The symptoms may include immediate reactions to the injection procedure (dizziness, shortness of breath, tachycardia, etc), or delayed reactions to the anesthetic (swelling, urticaria, etc). Although the true incidence of local anesthetic allergy is low, such a history often involves the patient's anxiety regarding the use of the drug in question, and the dentist's apprehension to treat the "problematic" patient. In such cases, hypnosis can play a major role in controlling pain and the associated distress. In the present article, the method concerning the implementation of hypnosis to induce local anesthesia is described and illustrated through case demonstrations.

Efficacy of benzocaine as an anesthetic for salmonid fishes

USGS Publications Warehouse

Gilderhus, P.A.

1989-01-01

Benzocaine was tested in the laboratory to determine the effective concentrations for anesthetizing juvenile chinook salmon Oncorhynchus tshawytscha an rainbow trout O. mykiss (formerly Salmo gairdneri ). Tests were conducted at three water temperatures, in waters ranging from very soft to very hard, and with groups of rainbow trout from 5 to 47 cm long and chinook salmon 20 cm long. Effective concentrations were defined as those that rendered the fish fully handleable in 3 min or less, allowed recovery of most fish within 10 min, and caused no mortality after 15-min exposures. Concentrations of 25-45 mg/L anesthetized both species over the entire range of conditions tested. Although efficacy was essentially unrelated to species or water quality, it was related to water temperature and size of fish; the concentrations of benzocaine required were highest at the lowest water temperature and for the largest fish.

Comparison of subarachnoid anesthetic effect of emulsified volatile anesthetics in rats

PubMed Central

Guo, Jiao; Zhou, Cheng; Liang, Peng; Huang, Han; Li, Fengshan; Chen, Xiangdong; Liu, Jin

2014-01-01

Spinal cord is an important target of volatile anesthetics in particular for the effect of immobility. Intrathecal injection of volatile anesthetics has been found to produce subarachnoid anesthesia. The present study was designed to compare spinal anesthetic effects of emulsified volatile anesthetics, and to investigate the correlation between their spinal effects and general effect of immobility. In this study, halothane, isoflurane, enflurane and sevoflurane were emulsified by 30% Intralipid. These emulsified volatile anesthetics were intravenously and intrathecally injected, respectively. ED50 of general anesthesia and EC50 of spinal anesthesia were determined. The durations of general and spinal anesthesia were recorded. Correlation analysis was applied to evaluate the anesthetic potency of volatile anesthetics between their spinal and general effects. ED50 of general anesthesia induced by emulsified halothane, isoflurane, enflurane and sevoflurane were 0.41 ± 0.07, 0.54 ± 0.07, 0.74 ± 0.11 and 0.78 ± 0.08 mmol/kg, respectively, with significant correlation to their inhaled MAC (R2 = 0.8620, P = 0.047). For intrathecal injection, EC50 of spinal anesthesia induced by emulsified halothane, isoflurane, enflurane and sevoflurane were 0.35, 0.27, 0.33 and 0.26 mol/L, respectively, which could be predicted by the product of inhaled MAC and olive oil/gas partition coefficients (R2 = 0.9627, P = 0.013). In conclusion, potency and efficacy of the four emulsified volatile anesthetics in spinal anesthesia were similar and could be predicted by the product of inhaled MAC and olive oil/gas partition coefficients (MAC × olive oil/gas partition coefficients). PMID:25674241

Mechanism of sodium channel block by local anesthetics, antiarrhythmics, and anticonvulsants

PubMed Central

Tikhonov, Denis B.

2017-01-01

Local anesthetics, antiarrhythmics, and anticonvulsants include both charged and electroneutral compounds that block voltage-gated sodium channels. Prior studies have revealed a common drug-binding region within the pore, but details about the binding sites and mechanism of block remain unclear. Here, we use the x-ray structure of a prokaryotic sodium channel, NavMs, to model a eukaryotic channel and dock representative ligands. These include lidocaine, QX-314, cocaine, quinidine, lamotrigine, carbamazepine (CMZ), phenytoin, lacosamide, sipatrigine, and bisphenol A. Preliminary calculations demonstrated that a sodium ion near the selectivity filter attracts electroneutral CMZ but repels cationic lidocaine. Therefore, we further docked electroneutral and cationic drugs with and without a sodium ion, respectively. In our models, all the drugs interact with a phenylalanine in helix IVS6. Electroneutral drugs trap a sodium ion in the proximity of the selectivity filter, and this same site attracts the charged group of cationic ligands. At this position, even small drugs can block the permeation pathway by an electrostatic or steric mechanism. Our study proposes a common pharmacophore for these diverse drugs. It includes a cationic moiety and an aromatic moiety, which are usually linked by four bonds. PMID:28258204

Mechanism of sodium channel block by local anesthetics, antiarrhythmics, and anticonvulsants.

PubMed

Tikhonov, Denis B; Zhorov, Boris S

2017-04-03

Local anesthetics, antiarrhythmics, and anticonvulsants include both charged and electroneutral compounds that block voltage-gated sodium channels. Prior studies have revealed a common drug-binding region within the pore, but details about the binding sites and mechanism of block remain unclear. Here, we use the x-ray structure of a prokaryotic sodium channel, NavMs, to model a eukaryotic channel and dock representative ligands. These include lidocaine, QX-314, cocaine, quinidine, lamotrigine, carbamazepine (CMZ), phenytoin, lacosamide, sipatrigine, and bisphenol A. Preliminary calculations demonstrated that a sodium ion near the selectivity filter attracts electroneutral CMZ but repels cationic lidocaine. Therefore, we further docked electroneutral and cationic drugs with and without a sodium ion, respectively. In our models, all the drugs interact with a phenylalanine in helix IVS6. Electroneutral drugs trap a sodium ion in the proximity of the selectivity filter, and this same site attracts the charged group of cationic ligands. At this position, even small drugs can block the permeation pathway by an electrostatic or steric mechanism. Our study proposes a common pharmacophore for these diverse drugs. It includes a cationic moiety and an aromatic moiety, which are usually linked by four bonds. © 2017 Tikhonov and Zhorov.

The Thermodynamics of General and Local Anesthesia

PubMed Central

Græsbøll, Kaare; Sasse-Middelhoff, Henrike; Heimburg, Thomas

2014-01-01

General anesthetics are known to cause depression of the freezing point of transitions in biomembranes. This is a consequence of ideal mixing of the anesthetic drugs in the membrane fluid phase and exclusion from the solid phase. Such a generic law provides physical justification of the famous Meyer-Overton rule. We show here that general anesthetics, barbiturates, and local anesthetics all display the same effect on melting transitions. Their effect is reversed by hydrostatic pressure. Thus, the thermodynamic behavior of local anesthetics is very similar to that of general anesthetics. We present a detailed thermodynamic analysis of heat capacity profiles of membranes in the presence of anesthetics. Using this analysis, we are able to describe experimentally observed calorimetric profiles and predict the anesthetic features of arbitrary molecules. In addition, we discuss the thermodynamic origin of the cutoff effect of long-chain alcohols and the additivity of the effect of general and local anesthetics. PMID:24853743

The Thermodynamics of General and Local Anesthesia

NASA Astrophysics Data System (ADS)

Græsbøll, Kaare; Sasse-Middelhoff, Henrike; Heimburg, Thomas

2014-05-01

General anesthetics are known to cause depression of the freezing point of transitions in biomembranes. This is a consequence of ideal mixing of the anesthetic drugs in the membrane fluid phase and exclusion from the solid phase. Such a generic law provides physical justification of the famous Meyer-Overton rule. We show here that general anesthetics, barbiturates and local anesthetics all display the same effect on melting transitions. Their effect is reversed by hydrostatic pressure. Thus, the thermodynamic behavior of local anesthetics is very similar to that of general anesthetics. We present a detailed thermodynamic analysis of heat capacity profiles of membranes in the presence of anesthetics. This analysis is able to describe experimentally observed calorimetric profiles and permits prediction of the anesthetic features of arbitrary molecules. In addition, we discuss the thermodynamic origin of the cutoff-effect of long-chain alcohols and the additivity of the effect of general and local anesthetics.

Influence of local anesthetics upon human polymorphonuclear leukocyte function in vitro. Reduction of lysosomal enzyme release and superoxide anion production

PubMed Central

1977-01-01

Cationic local anesthetics have been reported to influence cellular responses to surface stimuli by interfering with the function of microtubules and microfilaments. Since unimpaired microtubule and microfilament functions are required by human polymorphonuclear leukocytes in order to respond normally to surface stimulation, we have studied effects of the local anesthetic, tetracaine on the function and morphology of these cells in vitro. Tetracaine (0.25--1.0 mM) significantly reduced extracellular release of the lysosomal enzymes, beta-glucuronidase and lysozyme from polymorphonuclear leukocytes exposed to serum-treated zymosan (a particulate stimulus), zymosan- treated serum (a soluble stimulus), and to the surface-active lectin, concanavalin A. Tetracaine also significantly reduced superoixde anion production (superoxide dismutase-inhibitable cytochrome c reduction) by these cells. Tetrancaine was not cytotoxic and its effects could be reversed completely by washing cells once with buffer. Electron microscope examination of tetracaine-treated cells revealed marked alterations of surface membranes. Microtubules and microfilaments appeared normal in "resting" polymorphonuclear leukocytes, but the increase in microtubules normally observed in stimulated cells was not seen after tetracaine treatment. These results suggest that tetracaine interferes with those interactions between immune reactants and the polymorphonuclear leukocyte cell surface which provoke exocytosis and increased oxidative metabolism. PMID:195003

Hypersensitivity lo local anesthetics.

PubMed

Grzanka, Alicja; Wasilewska, Iwona; Śliwczyńska, Magdalena; Misiołek, Hanna

2016-01-01

Using local anaesthetics in daily practice, particularly by anaesthetists and dentists, is connected with the risk of side effects. Therefore, the observation of side effects, carrying out detailed research (according to the chart proposed in this study) and conducting specialist examinations is of the highest importance. There is a variety of side effects that could occur during local anaesthesia procedures, with the intensity ranging from clinically unimportant to life threatening. Clinicians' major concerns are the appearance of various hypersensitivity reactions, including anaphylaxis. Healthcare providers responsible for the administration of local anaesthetics should be able to detect hypersensitivity reactions to implement appropriate treatment and then choose highly selected diagnostic procedures. The final diagnosis should be based on specific medical history; documentation, including a description of the case and measurement of tryptase activity; skin tests; and provocation trials. Screening tests are not recommended in populations without hypersensitivity to local anaesthestics in their medical history.

Anesthetics lower Tc of a 2D miscibility critical point in the plasma membrane

NASA Astrophysics Data System (ADS)

Machta, Benjamin; Gray, Elly; Veatch, Sarah

2014-03-01

Many small hydrophobic molecules induce general anesthesia. Their efficacy as anesthetics has been shown to correlate both with their hydrophobicity and with their potency in inhibiting certain ligand gated ion channels. I will first report on our experiments on the effects that these molecules have on the two-dimensional miscibility critical point observed in cell derived vesicles (GPMVs). We show that anesthetics depress the critical temperature (Tc) of these GPMVs but do not strongly affect the ratio of phases found below Tc. The magnitude of this affect is consistent across the n-alcohols only when their concentration is rescaled by the median anesthetic concentration (AC50) for tadpole anesthesia and at AC50 we see a 4K downward shift in Tc. I will next present a model in which anesthetics interfere with native allosteric regulation of ligand gated channels by the critical membrane, showing that our observed change in critical properties could lead to the previously observed changes in channel conductance without a direct interaction between anesthetic molecules and their target proteins. Finally, I will discuss ongoing experiments that will clarify the role of this membrane effect in mediating the organism level anesthetic response.

Epidural analgesia with amide local anesthetics, bupivacaine, and ropivacaine in combination with fentanyl for labor pain relief: a meta-analysis.

PubMed

Li, Yiyang; Hu, Cong; Fan, Yanyan; Wang, Huixia; Xu, Hongmei

2015-03-29

The study compares the effectiveness of bupivacaine and fentanyl (BUPI-FEN) and ropivacaine and fentanyl (ROPI-EFN) in epidural analgesia for labor pain through a meta-analysis of relevant randomized clinical trials. Multiple electronic databases were searched using appropriate MeSH terms and keywords for original English language research papers published between 1990 and March 2014. Meta-analyses results were based on the mean differences between the groups as well as odds ratios where appropriate. Statistical heterogeneity amongst the included studies was tested by I^2 index. Nine studies that met the inclusion criteria were selected for analysis which consisted of 556 parturient patients. The duration of the second stage of labor was significantly shorter in the BUPI-FEN group by a mean of -6.87 (-10.98, -2.77; P<0.002). On the other hand, the ROPI-FEN group had a significantly lower incidence of motor blockade by a mean of 0.31 (0.18, 0.51; P<0.00001). A positive relationship between the amide local anesthetic concentration and the number of women having motor blockade was observed, but a negative relationship between fentanyl concentration and the number of women experiencing a motor block. Moreover, a positive correlation was found between the concentration of ropivacaine and the incidence of instrumental delivery and between the concentration of bupivacaine and the incidence of cesarean delivery. In combination with fentanyl, bupivacaine and ropivacaine exhibit comparable efficacy and safety. However, BUP-FEN analgesia led to a shortened second-stage labor and ROPI-FEN resulted in a significantly lower incidence of motor block.

Molecular genetic analysis of volatile-anesthetic action.

PubMed Central

Keil, R L; Wolfe, D; Reiner, T; Peterson, C J; Riley, J L

1996-01-01

The mechanism(s) and site(s) of action of volatile inhaled anesthetics are unknown in spite of the clinical use of these agents for more than 150 years. In the present study, the model eukaryote Saccharomyces cerevisiae was used to investigate the action of anesthetic agents because of its powerful molecular genetics. It was found that growth of yeast cells is inhibited by the five common volatile anesthetics tested (isoflurane, halothane, enflurane, sevoflurane, and methoxyflurane). Growth inhibition by the agents is relatively rapid and reversible. The potency of these compounds as yeast growth inhibitors directly correlates with their lipophilicity as is predicted by the Meyer-Overton relationship, which directly correlates anesthetic potency of agents and their lipophilicity. The effects of isoflurane on yeast cells were characterized in the most detail. Yeast cells survive at least 48 h in a concentration of isoflurane that inhibits colony formation. Mutants resistant to the growth-inhibitory effects of isoflurane are readily selected. The gene identified by one of these mutations, zzz4-1, has been cloned and characterized. The predicted ZZZ4 gene product has extensive homology to phospholipase A2-activating protein, a GO effector protein of mice. Both zzz4-1 and a deletion of ZZZ4 confer resistance to all five of the agents tested, suggesting that signal transduction may be involved in the response of these cells to volatile anesthetics. PMID:8668160

The Pathophysiology of Early Hypotension Following Epinephrine-containing Local Anesthetic Infiltration of the Nasal Mucosa in Patients Undergoing Endoscopic Transsphenoidal Hypophysectomy: A Prospective, Observational Study.

PubMed

Wiles, Matthew D; Sanders, Matthew I; Sinha, Saurabh; Mirza, Showkat; Andrzejowski, John C

2017-07-01

In patients undergoing endoscopic transsphenoidal hypophysectomy, the nasal mucosa is often infiltrated with local anesthetic solutions that contain epinephrine to aid hemostasis. This may, however, result in hemodynamic changes, especially hypotension. We characterized the cardiovascular changes using a LiDCOrapid monitor in 13 patients after the infiltration of 4% articaine containing 1:200,000 epinephrine. Nine (69%) had a >20% decrease in mean arterial pressure at a median time of 116 seconds after the infiltration of articaine with epinephrine. Analysis of the cardiac output data revealed that this was caused by a sustained reduction in systemic vascular resistance. The arterial blood pressure normalized over a period of 60 to 90 seconds secondary to increases in stroke volume and heart rate producing an elevation in cardiac output. Transient hypotension following the infiltration of epinephrine-containing local anesthetics may be caused by epinephrine stimulation of β2-adrenoceptors producing vasodilation.

Mechanisms underlying changes in indomethacin solubility with local anesthetics and related basic additives

NASA Astrophysics Data System (ADS)

Shimada, Yohsuke; Tateuchi, Ryo; Chatani, Hitoshi; Goto, Satoru

2018-03-01

Indomethacin (IND), an acidic nonsteroidal anti-inflammatory drug, and lidocaine (LID), a local anesthetic (LA), form a eutectic complex when mixed, with a lower melting point. The aqueous solubility of the mixture is greater than that of IND or LID alone, improving the bioavailability of IND. Therefore, IND and LID can be used to model changes in efficacy caused by physicochemical interactions between drugs. In this study, the intermolecular interactions between IND and structurally similar LAs were examined by measuring solubility and analyzing thermodynamics using differential scanning calorimetry. The results indicate that the solubility of IND (log S'IND) varies with LA hydrophobicity. Reductions in melting point resulting from mixing IND and LAs contributed to changes in IND solubility, attributable to direct intermolecular interactions between IND and the LAs. In addition, binding energy of IND-LA as in water was calculated, and the values were correlating with the solubility of IND in experiments. Understanding these interactions will help address some of the problems encountered in polypharmacy.

Neurometric assessment of intraoperative anesthetic

DOEpatents

Kangas, L.J.; Keller, P.E.

1998-07-07

The present invention is a method and apparatus for collecting EEG data, reducing the EEG data into coefficients, and correlating those coefficients with a depth of unconsciousness or anesthetic depth, and which obtains a bounded first derivative of anesthetic depth to indicate trends. The present invention provides a developed artificial neural network based method capable of continuously analyzing EEG data to discriminate between awake and anesthetized states in an individual and continuously monitoring anesthetic depth trends in real-time. The present invention enables an anesthesiologist to respond immediately to changes in anesthetic depth of the patient during surgery and to administer the correct amount of anesthetic. 7 figs.

Neurometric assessment of intraoperative anesthetic

DOEpatents

Kangas, Lars J.; Keller, Paul E.

1998-01-01

The present invention is a method and apparatus for collecting EEG data, reducing the EEG data into coefficients, and correlating those coefficients with a depth of unconsciousness or anesthetic depth, and which obtains a bounded first derivative of anesthetic depth to indicate trends. The present invention provides a developed artificial neural network based method capable of continuously analyzing EEG data to discriminate between awake and anesthetized states in an individual and continuously monitoring anesthetic depth trends in real-time. The present invention enables an anesthesiologist to respond immediately to changes in anesthetic depth of the patient during surgery and to administer the correct amount of anesthetic.

Methemoglobin Levels in Generally Anesthetized Pediatric Dental Patients Receiving Prilocaine Versus Lidocaine

PubMed Central

Gutenberg, Lauren L.; Chen, Jung-Wei; Trapp, Larry

2013-01-01

The purpose of this study was to measure and compare peak methemoglobin levels and times to peak methemoglobin levels following the use of prilocaine and lidocaine in precooperative children undergoing comprehensive dental rehabilitation under general anesthesia. Ninety children, 3–6 years of age, undergoing dental rehabilitation under general anesthesia were enrolled and randomly assigned into 3 equal groups: group 1, 4% prilocaine plain, 5 mg/kg; group 2, 2% lidocaine with 1 : 100,000 epinephrine, 2.5 mg/kg; and group 3, no local anesthetic. Subjects in groups 1 and 2 were administered local anesthetic prior to restorative dental treatment. Methemoglobin levels (SpMET) were measured and recorded throughout the procedure using a Masimo Radical-7 Pulse Co-Oximeter (Masimo Corporation, Irvine, Calif, RDS-1 with SET software with methemoglobin interface). Data were analyzed using chi-square, one-way analysis of variance (ANOVA), and Pearson correlation (significance of P < .05). Group 1 had a significantly higher mean peak SpMET level at 3.55% than groups 2 and 3 at 1.63 and 1.60%, respectively. The mean time to peak SpMET was significantly shorter for group 3 at 29.50 minutes than that of group 1 at 62.73 and group 2 at 57.50 minutes. Prilocaine, at 5 mg/kg in pediatric dental patients, resulted in significantly higher peak SpMET levels than lidocaine and no local anesthetic. In comparison to no local anesthetic, the administration of prilocaine and lidocaine caused peak SpMET levels to occur significantly later in the procedure. PMID:24010987

Influence of inhalation anesthetics on ion transport across a planar bilayer lipid membrane.

PubMed

Hichiri, Kei; Shirai, Osamu; Kano, Kenji

2012-01-01

Ion transport from one aqueous phase (W1) to another (W2) across a planar bilayer lipid membrane (BLM) in the presence of inhalation anesthetics was electrochemically investigated. In the absence of inhalation anesthetics in the BLM system, no ion transport current flowed between W1 and W2 across the BLM. When inhalation anesthetics such as halothane, chloroform, diethyl ether and trichloroethylene were added to the two aqueous phases or the BLM, the ion transport current quite clearly appeared. When the ratio of the concentration of KCl or NaCl in W1 to that in W2 was varied, the zero current potential across the BLM was shifted. By considering the magnitude of the potential shift, we concluded that the ion transport current can be predominantly ascribed to the transport of Cl(-) across the BLM. Since the dielectric constants of these anesthetics are larger than that of the inner hydrophobic domain of the BLM, the concentration of hydrophilic electrolyte ions in the BLM increases with the increase in the dielectric constant of the inner hydrophobic domain caused by addition of these anesthetics. These situations lead to an increase in the ion permeability coefficient.

Anesthetic efficacy of the supplemental intraosseous injection for teeth with irreversible pulpitis.

PubMed

Parente, S A; Anderson, R W; Herman, W W; Kimbrough, W F; Weller, R N

1998-12-01

The purpose of this study was to determine the efficacy of a supplemental intraosseous injection (IOI) of 2% lidocaine with 1:100,000 epinephrine using the Stabident device, after conventional anesthetic methods had failed. Patients who experienced pain during endodontic access and required a supplemental IOI using 0.45 to 0.90 ml of the local anesthetic were identified. All 37 of the patients treated had teeth diagnosed with irreversible pulpitis. Thirty-four of the teeth were mandibular posterior teeth, 2 were maxillary posterior teeth, and 1 was a maxillary anterior tooth. Patients with maxillary teeth had received infiltration anesthesia, and those with mandibular teeth had received an inferior alveolar nerve block in conjunction with long buccal infiltration. A minimum of 3.6 ml of local anesthetic was used with the conventional techniques. Modified visual analogue scales, coupled with operator evaluations, were used to measure success. The Stabident IOI was an effective supplemental anesthetic technique in 89% (+/- 5.1) or 33/37 patients evaluated. The 95% confidence interval was 74 to 97%. The IOI was successful in 91% (+/- 4.9) of the mandibular posterior teeth (31/34), and 67% of the maxillary teeth (2/3).

Periodontal ligament and intraosseous anesthetic injection techniques: alternatives to mandibular nerve blocks.

PubMed

Moore, Paul A; Cuddy, Michael A; Cooke, Matthew R; Sokolowski, Chester J

2011-09-01

and Overview. The provision of mandibular anesthesia traditionally has relied on nerve block anesthetic techniques such as the Halsted, the Gow-Gates and the Akinosi-Vazirani methods. The authors present two alternative techniques to provide local anesthesia in mandibular teeth: the periodontal ligament (PDL) injection and the intraosseous (IO) injection. The authors also present indications for and complications associated with these techniques. The PDL injection and the IO injection are effective anesthetic techniques for managing nerve block failures and for providing localized anesthesia in the mandible. Dentists may find these techniques to be useful alternatives to nerve block anesthesia.

Neurometric assessment of intraoperative anesthetic

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kangas, L.J.; Keller, P.E.

1998-07-07

The present invention is a method and apparatus for collecting EEG data, reducing the EEG data into coefficients, and correlating those coefficients with a depth of unconsciousness or anesthetic depth, and which obtains a bounded first derivative of anesthetic depth to indicate trends. The present invention provides a developed artificial neural network based method capable of continuously analyzing EEG data to discriminate between awake and anesthetized states in an individual and continuously monitoring anesthetic depth trends in real-time. The present invention enables an anesthesiologist to respond immediately to changes in anesthetic depth of the patient during surgery and to administermore » the correct amount of anesthetic. 7 figs.« less

QSPR/QSAR in N-[(dimethylamine)methyl] benzamides substituents groups influence upon electronic distribution and local anesthetics activity.

PubMed

Tavares, Leoberto Costa; do Amaral, Antonia Tavares

2004-03-15

It was determined, with a systematic mode, the carbonyl group frequency in the region of the infrared of N-[(dimethylamine)methyl] benzamides 4-substituted (set A) and their hydrochlorides (set B), that had its local anesthetical activity evaluated. The application of the Hammett equation considering the values of the absorption frequency of carbonyl group, nu(C=O,) using the electronic constants sigma, sigma(I), sigma(R), I and R leads to meaningful correlation. The nature and the contribution of substituent group electronic effects on the polarity of the carbonyl group was also analyzed. The use of the nu(C=O) as an experimental electronic parameter for QSPR studies was validated.

Differential General Anesthetic Effects on Microglial Cytokine Expression

PubMed Central

Ye, Xuefei; Lian, Qingquan; Eckenhoff, Maryellen F.; Eckenhoff, Roderic G.; Pan, Jonathan Z.

2013-01-01

Post-operative cognitive dysfunction has been widely observed, especially in older patients. An association of post-operative cognitive dysfunction with the neurodegenerative diseases, such as Alzheimer's disease, has been suggested. Neuroinflammation contributes to Alzheimer pathology, through elevated pro-inflammatory cytokines and microglial activation in the CNS leading to neuronal damage, synaptic disruption and ultimately cognitive dysfunction. We compare the effects of three different, clinically-used, anesthetics on microglial activation with, and without, the prototypical inflammatory trigger, lipopolysaccharide (LPS). Microglial BV-2 cell cultures were first exposed to isoflurane, sevoflurane (each at 2 concentrations) or propofol for 6 h, and cytokine levels measured in lysates and media. The same experiments were repeated after 1 h LPS pre-treatment. We found; 1) anesthetics alone have either no or only a small effect on cytokine expression; 2) LPS provoked a large increase in microglia cytokine expression; 3) the inhaled anesthetics either had no effect on LPS-evoked responses or enhanced it; 4) propofol nearly eliminated the LPS pro-inflammatory cytokine response and improved cell survival as reflected by lactate dehydrogenase release. These data suggest that propofol may be a preferred anesthetic when it is desirable to minimize neuroinflammation. PMID:23382826

Local Anesthetic Microencapsulation.

DTIC Science & Technology

1983-11-04

tollowing I.M. injection of microencapsulated lidocaine and etidocaine than following solution injections. Local toxicity of these microcapsule injections...Distribution 41 Table 12 Processing Summary of Lidocaine (Base) 43 Microencapsulation Table 13 Lidocaine (Base) Microcapsule Size 44 Distribution...Table 14 Processing Summary of Et’idocaine-HCl 45 Microencapsulation Table 15 Etidocaine-HCl Microcapsule Size 47 Distribution Table 16 Process Summary

Anesthetic Requirement is Increased in Redheads

PubMed Central

Liem, Edwin B.; Lin, Chun–Ming; Suleman, Mohammad–Irfan; Doufas, Anthony G.; Gregg, Ronald G.; Veauthier, Jacqueline M.; Loyd, Gary

2005-01-01

Background: Age and body temperature alter inhalational anesthetic requirement; however, no human genotype is associated with inhalational anesthetic requirement. There is an anecdotal impression that anesthetic requirement is increased in redheads. Furthermore, red hair results from distinct mutations of the melanocortin-1 receptor. We thus tested the hypothesis that the requirement for the volatile anesthetic desflurane is greater in natural redhead than in dark-haired women. Methods: We studied healthy women with bright red (n=10) or dark (n=10) hair. Blood was sampled for subsequent analyses of melanocortin-1 receptor alleles. Anesthesia was induced with sevoflurane and maintained with desflurane randomly set at an end-tidal concentration between 5.5 and 7.5%. After an equilibration period, a noxious electrical stimulation (100 Hz, 70 mA) was transmitted through bilateral intradermal needles. If the volunteer moved in response to stimulation, desflurane was increased by 0.5%; otherwise it was decreased by 0.5%. This was continued until volunteers “crossed-over” from movement to non-movement (or vice versa) four times. Individual logistic regression curves were used to determine desflurane requirement (P50). Desflurane requirements in the two groups were compared using Mann-Whitney nonparametric two-sample test; P < 0.05 was considered statistically significant. Results: The desflurane requirement in redheads (6.2 volume-percent [95% CI, 5.9 - 6.5]) was significantly greater than in dark-haired women (5.2 volume-percent [4.9 – 5.5], P = 0.0004). Nine of 10 redheads were either homozygous or compound heterozygotes for mutations on the melanocortin-1 receptor gene. Conclusions: Red hair appears to be a distinct phenotype linked to anesthetic requirement in humans that can also be traced to a specific genotype. PMID:15277908

Development of bupivacaine decorated reduced graphene oxide and its local anesthetic effect-In vivo study.

PubMed

Zhang, Zhi; Zhang, Xin; Li, Aixiang; Ma, Chuangen

2018-03-01

The present works aims to develop bupivacaine modified reduced graphene oxide (BPV/RGO), and comparative evaluation of their anesthetic effect with free bupivacaine (BPV). The prepared BPV/RGO was studied by using various spectroscopic and microscopic characterization studies. In vitro drug release from BPV/RGO was studied using HPLC analysis. The cytotoxicity of BPV/RGO was studied against fibroblast (3T3) cells. In vivo evaluation of anesthetic effects was performed on animal models. BPV/RGO showed a prolonged in vitro release and lower cytotoxicity when compared to free BPV. Also, BPV/RGO showed a significantly prolonged analgesic effect when compared to free BPV. Further, the prepared BPV/RGO drug delivery system demonstrated to function as gifted to overcome the drawbacks of free BPV and other available drug delivery systems by prolonging the anesthetic effect with poor cytotoxicity. Copyright © 2018. Published by Elsevier B.V.

Prediction of compensatory hyperhidrosis with botulinum toxin A and local anesthetic.

PubMed

Jeong, Jin Yong; Park, Soo Seog; Sim, Sung Bo; Jo, Keon Hyon; Lee, Jongho; Oh, Saecheol; Shin, Jae Seong

2015-08-01

Compensatory hyperhidrosis (CH) is one of the most problematic complications of sympathectomy, which occurs often and is hard to treat. A predictive procedure (PP) for CH can help patients experience compensatory sweating before sympathectomy to determine whether or not to perform sympathectomy. Our study aimed to evaluate the CH after the PP and sympathectomy in patients with primary palmar hyperhidrosis using multiple drugs. We reviewed 83 patients who underwent a PP between July 2009 and August 2013 with primary palmar hyperhidrosis. In group A, we used levobupivacaine (n = 39). In group B, we used botulinum toxin A plus ropivacaine for the PP in group B (n = 44). The CH rate after the PP was 44 % (group A) and 25 % (group B), and after sympathectomy 80 % (group A) and 75 % (group B). The prediction value between the PP and the sympathectomy was statistically significant in group A (p < 0.05). The positive prediction rate was 73 % and the negative prediction rate was 27 % in group A. Local anesthetic alone has a better predictive value. From our finding, patients should be made aware that CH after sympathectomy is less severe in 73 % of cases than that experienced in the PP.

Effects of Topical Anesthetics on Pullularia pullulans and Debaryomyces hansenii

PubMed Central

Merdinger, Emanuel; Guthmann, Walter S.; Mangine, Francis W.

1969-01-01

The inhibitory effects of three topical anesthetics of various concentrations on the growth of Pullularia pullulans, Debaryomyces hansenii, and on pigment production by P. pullulans were investigated. The topical anesthetics were benoxinate hydrochloride, proparacaine hydrochloride, and tetracaine hydrochloride. In decreasing order, the inhibiting effects of the drugs on growth were benoxinate, tetracaine, and proparacaine for P. pullulans, and tetracaine, benoxinate, and proparacaine for D. hansenii. The pigment formation in P. pullulans was inhibited by the three drugs. PMID:5392897

Effects of topical anesthetics on Pullalaria pullulans and Debaryomyces hansenii.

PubMed

Merdinger, E; Guthmann, W S; Mangine, F W

1969-09-01

The inhibitory effects of three topical anesthetics of various concentrations on the growth of Pullularia pullulans, Debaryomyces hansenii, and on pigment production by P. pullulans were investigated. The topical anesthetics were benoxinate hydrochloride, proparacaine hydrochloride, and tetracaine hydrochloride. In decreasing order, the inhibiting effects of the drugs on growth were benoxinate, tetracaine, and proparacaine for P. pullulans, and tetracaine, benoxinate, and proparacaine for D. hansenii. The pigment formation in P. pullulans was inhibited by the three drugs.

Cell shape changes induced by cationic anesthetics

PubMed Central

1976-01-01

The effects of local anesthetics on cultivated macrophages were studied in living preparations and recorded in still pictures and time-lapse cine-micrographs. Exposure to 12mM lidocaine or 1.5 mM tetracaine resulted in rounding in 10-15 min. Rounding was characterized by cell contraction, marked increase in retraction fibrils, withdrawal of cell processes, and, in late stages, pulsation-like activity and zeiosis. Cells showed appreciable membrane activity as they rounded. Respreading was complete within 15 min of perfusion in drug-free medium and entailed a marked increase in surface motility over control periods. As many as eight successive cycles of rounding and spreading were obtained with lidocaine without evidence of cell damage. The effects of anesthetics were similar to those observed with EDTA, but ethylene- glycol-bis(beta-aminoethylether)-N, N'-tetraacetic acid-Mg was ineffective. Rounding was also induced by benzocaine, an anesthetic nearly uncharged at pH 7.0. Quaternary (nondischargeable) compounds were of low activity, presumably because they are slow permeants. Lidocaine induced rounding at 10 degrees C and above but was less effective at 5 degrees C and ineffective at 0 degrees C. Rounding by the anesthetic was also obtained in media depleted or Na or enriched with 10 mM Ca or Mg. The latter finding, together with the failure of tetrodotoxin to induce rounding, suggests that the anesthetic effect is unrelated to inhibition of sodium conductance. It is possible that the drugs influence divalent ion fluxes or some component of the contractile cells' machinery, but a metabolic target of action cannot yet be excluded. PMID:814194

Epidural Analgesia with Amide Local Anesthetics, Bupivacaine, and Ropivacaine in Combination with Fentanyl for Labor Pain Relief: A Meta-Analysis

PubMed Central

Li, Yiyang; Hu, Cong; Fan, Yanyan; Wang, Huixia; Xu, Hongmei

2015-01-01

Background The study compares the effectiveness of bupivacaine and fentanyl (BUPI-FEN) and ropivacaine and fentanyl (ROPI-EFN) in epidural analgesia for labor pain through a meta-analysis of relevant randomized clinical trials. Material/Methods Multiple electronic databases were searched using appropriate MeSH terms and keywords for original English language research papers published between 1990 and March 2014. Meta-analyses results were based on the mean differences between the groups as well as odds ratios where appropriate. Statistical heterogeneity amongst the included studies was tested by I2 index. Results Nine studies that met the inclusion criteria were selected for analysis which consisted of 556 parturient patients. The duration of the second stage of labor was significantly shorter in the BUPI-FEN group by a mean of −6.87 (−10.98, −2.77; P<0.002). On the other hand, the ROPI-FEN group had a significantly lower incidence of motor blockade by a mean of 0.31 (0.18, 0.51; P<0.00001). A positive relationship between the amide local anesthetic concentration and the number of women having motor blockade was observed, but a negative relationship between fentanyl concentration and the number of women experiencing a motor block. Moreover, a positive correlation was found between the concentration of ropivacaine and the incidence of instrumental delivery and between the concentration of bupivacaine and the incidence of cesarean delivery. Conclusions In combination with fentanyl, bupivacaine and ropivacaine exhibit comparable efficacy and safety. However, BUP-FEN analgesia led to a shortened second-stage labor and ROPI-FEN resulted in a significantly lower incidence of motor block. PMID:25816849

Mechanisms of Anesthetic Action and Neurotoxicity: Lessons from Molluscs

PubMed Central

Armstrong, Ryden; Riaz, Saba; Hasan, Sean; Iqbal, Fahad; Rice, Tiffany; Syed, Naweed

2018-01-01

Anesthesia is a prerequisite for most surgical procedures in both animals and humans. Significant strides have been made in search of effective and safer compounds that elicit rapid induction and recovery from anesthesia. However, recent studies have highlighted possible negative effects of several anesthetic agents on the developing brain. The precise nature of this cytotoxicity remains to be determined mainly due to the complexity and the intricacies of the mammalian brain. Various invertebrates have contributed significantly toward our understanding of how both local and general anesthetics affect intrinsic membrane and synaptic properties. Moreover, the ability to reconstruct in vitro synapses between individually identifiable pre- and postsynaptic neurons is a unique characteristic of molluscan neurons allowing us to ask fundamental questions vis-à-vis the long-term effects of anesthetics on neuronal viability and synaptic connectivity. Here, we highlight some of the salient aspects of various molluscan organisms and their contributions toward our understanding of the fundamental mechanisms underlying the actions of anesthetic agents as well as their potential detrimental effects on neuronal growth and synaptic connectivity. We also present some novel preliminary data regarding a newer anesthetic agent, dexmedetomidine, and its effects on synaptic transmission between Lymnaea neurons. The findings presented here underscore the importance of invertebrates for research in the field of anesthesiology while highlighting their relevance to both vertebrates and humans. PMID:29410627

Comparison of the efficacy and safety of 2% lidocaine HCl with different epinephrine concentration for local anesthesia in participants undergoing surgical extraction of impacted mandibular third molars

PubMed Central

Karm, Myong-Hwan; Park, Fiona Daye; Kang, Moonkyu; Kim, Hyun Jeong; Kang, Jeong Wan; Kim, Seungoh; Kim, Yong-Deok; Kim, Cheul-Hong; Seo, Kwang-Suk; Kwon, Kyung-Hwan; Kim, Chul-Hwan; Lee, Jung-Woo; Hong, Sung-Woon; Lim, Mi Hyoung; Nam, Seung Kwan; Cho, Jae Min

2017-01-01

Abstract Background: The most commonly impacted tooth is the third molar. An impacted third molar can ultimately cause acute pain, infection, tumors, cysts, caries, periodontal disease, and loss of adjacent teeth. Local anesthesia is employed for removing the third molar. This study aimed to evaluate the efficacy and safety of 2% lidocaine with 1:80,000 or 1:200,000 epinephrine for surgical extraction of bilateral impacted mandibular third molars. Methods: Sixty-five healthy participants underwent surgical extraction of bilateral impacted mandibular third molars in 2 separate visits while under local anesthesia with 2% lidocaine with different epinephrine concentration (1:80,000 or 1:200,000) in a double-blind, randomized, crossover trial. Visual analog scale pain scores obtained immediately after surgical extraction were primarily evaluated for the 2 groups receiving different epinephrine concentrations. Visual analog scale pain scores were obtained 2, 4, and 6 hours after administering an anesthetic. Onset and duration of analgesia, onset of pain, intraoperative bleeding, operator's and participant's overall satisfaction, drug dosage, and hemodynamic parameters were evaluated for the 2 groups. Results: There were no statistically significant differences between the 2 groups in any measurements except hemodynamic factors (P >.05). Changes in systolic blood pressure and heart rate following anesthetic administration were significantly greater in the group receiving 1:80,000 epinephrine than in that receiving 1:200,000 epinephrine (P ≤.01). Conclusion: The difference in epinephrine concentration between 1:80,000 and 1:200,000 in 2% lidocaine liquid does not affect the medical efficacy of the anesthetic. Furthermore, 2% lidocaine with 1:200,000 epinephrine has better safety with regard to hemodynamic parameters than 2% lidocaine with 1:80,000 epinephrine. Therefore, we suggest using 2% lidocaine with 1:200,000 epinephrine rather than 2% lidocaine with 1

Scientometrics of anesthetic drugs and their techniques of administration, 1984-2013.

PubMed

Vlassakov, Kamen V; Kissin, Igor

2014-01-01

The aim of this study was to assess progress in the field of anesthetic drugs over the past 30 years using scientometric indices: popularity indices (general and specific), representing the proportion of articles on a drug relative to all articles in the field of anesthetics (general index) or the subfield of a specific class of anesthetics (specific index); index of change, representing the degree of growth in publications on a topic from one period to the next; index of expectations, representing the ratio of the number of articles on a topic in the top 20 journals relative to the number of articles in all (>5,000) biomedical journals covered by PubMed; and index of ultimate success, representing a publication outcome when a new drug takes the place of a common drug previously used for the same purpose. Publications on 58 topics were assessed during six 5-year periods from 1984 to 2013. Our analysis showed that during 2009-2013, out of seven anesthetics with a high general popularity index (≥2.0), only two were introduced after 1980, ie, the inhaled anesthetic sevoflurane and the local anesthetic ropivacaine; however, only sevoflurane had a high index of expectations (12.1). Among anesthetic adjuncts, in 2009-2013, only one agent, sugammadex, had both an extremely high index of change (>100) and a high index of expectations (25.0), reflecting the novelty of its mechanism of action. The index of ultimate success was positive with three anesthetics, ie, lidocaine, isoflurane, and propofol, all of which were introduced much longer than 30 years ago. For the past 30 years, there were no new anesthetics that have produced changes in scientometric indices indicating real progress.

Renal effects of carprofen administered to healthy dogs anesthetized with propofol and isoflurane.

PubMed

Ko, J C; Miyabiyashi, T; Mandsager, R E; Heaton-Jones, T G; Mauragis, D F

2000-08-01

To evaluate renal effects of carprofen in healthy dogs following general anesthesia. Randomized clinical trial. 10 English hound dogs (6 females and 4 males). Dogs were randomly assigned to control (n = 5) or carprofen (5) groups. Anesthesia was induced with propofol (6 to 8 mg/kg [2.7 to 3.6 mg/lb] of body weight, i.v.) and maintained with isoflurane (end-tidal concentration, 2.0%). Each dog underwent two 60-minute anesthetic episodes with 1 week between episodes, and mean arterial blood pressure was maintained between 60 and 90 mm Hg during each episode. Dogs in the carprofen group received carprofen (2.2 mg/kg [1 mg/lb], p.o.) at 9:00 AM and 6:00 PM the day before and at 7:00 AM the day of the second anesthetic episode. Glomerular filtration rates (GFR) were determined during each anesthetic episode by use of renal scintigraphy. Serum creatinine and BUN concentrations and the urine gamma-glutamyltransferase-to-creatinine concentration (urine GGT:creatinine) ratio were determined daily for 2 days before and 5 days after general anesthesia. Significant differences were not detected in BUN and serum creatinine concentrations, urine GGT:creatinine ratio, and GFR either between or within treatment groups over time. Carprofen did not significantly alter renal function in healthy dogs anesthetized with propofol and isoflurane. These results suggest that carprofen may be safe to use for preemptive perioperative analgesia, provided that normal cardiorespiratory function is maintained.

Occupational exposure to anesthetics leads to genomic instability, cytotoxicity and proliferative changes.

PubMed

Souza, Kátina M; Braz, Leandro G; Nogueira, Flávia R; Souza, Marajane B; Bincoleto, Lahis F; Aun, Aline G; Corrente, José E; Carvalho, Lídia R; Braz, José Reinaldo C; Braz, Mariana G

Data on the genotoxic and mutagenic effects of occupational exposure to the most frequently used volatile anesthetics are limited and controversial. The current study is the first to evaluate genomic instability, cell death and proliferative index in exfoliated buccal cells (EBC) from anesthesiologists. We also evaluated DNA damage and determined the concentrations of the anesthetic gases most commonly used in operating rooms. This study was conducted on physicians who were allocated into two groups: the exposed group, which consisted of anesthesiologists who had been exposed to waste anesthetic gases (isoflurane, sevoflurane, desflurane and nitrous oxide - N 2 O) for at least two years; and the control group, which consisted of non-exposed physicians matched for age, sex and lifestyle with the exposed group. Venous blood and EBC samples were collected from all participants. Basal DNA damage was evaluated in lymphocytes by the comet assay, whereas the buccal micronucleus (MN) cytome (BMCyt) assay was applied to evaluate genotoxic and cytotoxic effects. The concentrations of N 2 O and anesthetics were measured via a portable infrared spectrophotometer. The average concentration of waste gases was greater than 5 parts per million (ppm) for all of the halogenated anesthetics and was more than 170ppm for N 2 O, expressed as a time-weighted average. There was no significant difference between the groups in relation to lymphocyte DNA damage. The exposed group had higher frequencies of MN, karyorrhexis and pyknosis, and a lower frequency of basal cells compared with the control group. In conclusion, exposure to modern waste anesthetic gases did not induce systemic DNA damage, but it did result in genomic instability, cytotoxicity and proliferative changes, which were detected in the EBC of anesthesiologists. Thus, these professionals can be considered at risk for developing genetic alterations resulting from occupational exposure to these gases, suggesting the need to

A randomized controlled trial comparing Ametop™ with placebo for reducing pain associated with local anesthetic skin infiltration before neuraxial anesthesia in parturients.

PubMed

Kavanagh, T; Dube, A; Albert, A; Gunka, V

2016-08-01

Between 10-22% of the general population experience needle phobia. Needle phobic parturients are at increased risk of adverse outcomes. We assessed the efficacy of topical Ametop™ (tetracaine 4%) gel in reducing the pain associated with local anesthetic skin infiltration before neuraxial block in non-laboring women. This was a prospective, randomized, double-blind, placebo-controlled study. Ametop™ or placebo was applied to the skin of the lower back at least 20min before neuraxial block using a standardized technique with 1% lidocaine skin infiltration. The primary outcome was numeric pain score (0-10) 30s after lidocaine infiltration. Groups were compared using Welch's t-test. Thirty-six subjects in each group were analyzed. There was a statistically significant difference in the mean (standard deviation) pain score between the Ametop™ and the placebo groups: 2.36±1.80 and 3.51±2.22, respectively (P=0.019). There were no significant adverse events. The mean numeric pain score in the Ametop™ group was 33% lower compared to the placebo group. Topical Ametop™ gel applied at least 20min before local anesthetic infiltration of the skin prior to neuraxial block in elective cesarean delivery may be a useful adjunct in needle phobic women. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

21 CFR 868.5880 - Anesthetic vaporizer.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Anesthetic vaporizer. 868.5880 Section 868.5880...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5880 Anesthetic vaporizer. (a) Identification. An anesthetic vaporizer is a device used to vaporize liquid anesthetic and deliver a controlled...

21 CFR 868.5880 - Anesthetic vaporizer.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Anesthetic vaporizer. 868.5880 Section 868.5880...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5880 Anesthetic vaporizer. (a) Identification. An anesthetic vaporizer is a device used to vaporize liquid anesthetic and deliver a controlled...

21 CFR 868.5880 - Anesthetic vaporizer.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Anesthetic vaporizer. 868.5880 Section 868.5880...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5880 Anesthetic vaporizer. (a) Identification. An anesthetic vaporizer is a device used to vaporize liquid anesthetic and deliver a controlled...

21 CFR 868.5880 - Anesthetic vaporizer.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Anesthetic vaporizer. 868.5880 Section 868.5880...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5880 Anesthetic vaporizer. (a) Identification. An anesthetic vaporizer is a device used to vaporize liquid anesthetic and deliver a controlled...

21 CFR 868.5880 - Anesthetic vaporizer.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Anesthetic vaporizer. 868.5880 Section 868.5880...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5880 Anesthetic vaporizer. (a) Identification. An anesthetic vaporizer is a device used to vaporize liquid anesthetic and deliver a controlled...

Effects of Different Anesthetics on Oscillations in the Rat Olfactory Bulb

PubMed Central

Li, Anan; Zhang, Lei; Liu, Min; Gong, Ling; Liu, Qing; Xu, Fuqiang

2012-01-01

Different types of oscillations in the olfactory bulb (OB), including θ (1 to 4 and 5 to 12 Hz), β (13 to 30 Hz), and γ oscillations (31 to 64 and 65 to 90 Hz), are important in olfactory information processing and olfactory-related functions and have been investigated extensively in recent decades. The awake and anesthetized states, 2 different brain conditions, are used widely in electrophysiologic studies of OB. Chloral hydrate, pentobarbital, and urethane are commonly used anesthetics in these studies. However, the influence of these anesthetics on the oscillations has not been reported. In the present study, we recorded the local field potential (LFP) in the OB of rats that were freely moving or anesthetized with these agents. Chloral hydrate and pentobarbital had similar effects: they slightly affected the power of θ oscillations; significantly increased the power of β oscillations; significantly decreased the power of γ oscillations, and showed similar recovery of γ oscillations. Urethane had very different effects: it significantly increased oscillations at 1 to 4 Hz but decreased those at 5 to 12 Hz, decreased β and γ oscillations, and showed no overt recovery in γ oscillations. These results provide experimental evidence of different effects of various anesthetics on OB oscillations and suggest that the choice of anesthetic should consider the experimental application. PMID:23043811

Mass spectrometer with a membrane interface for intraoperative monitoring the elimination of inhalation anesthetic and CO2 through the skin

NASA Astrophysics Data System (ADS)

Elizarov, A. Yu.; Ershov, T. D.; Levshankov, A. I.; Cherebillo, V. Yu.

2016-11-01

A new method is implemented in order to measure the concentration of CO2 and inhalation anesthetic sevoflurane eliminated through the skin during surgery. The concentration of inhalation anesthetic has been measured during general combined anesthesia (sevoflurane, fentanyl) and total intravenous anesthesia (propofol, fentanyl). The dependence of the concentration of CO2 and the inhalation anesthetic from the relaxation of smooth muscles in the walls of blood vessels under the effect of sevoflurane and propofol and on the stress response to surgical injury has been revealed for the first time.

21 CFR 872.6100 - Anesthetic warmer.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Anesthetic warmer. 872.6100 Section 872.6100 Food... DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6100 Anesthetic warmer. (a) Identification. An anesthetic warmer is an AC-powered device into which tubes containing anesthetic solution are intended to be...

21 CFR 872.6100 - Anesthetic warmer.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Anesthetic warmer. 872.6100 Section 872.6100 Food... DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6100 Anesthetic warmer. (a) Identification. An anesthetic warmer is an AC-powered device into which tubes containing anesthetic solution are intended to be...

21 CFR 872.6100 - Anesthetic warmer.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Anesthetic warmer. 872.6100 Section 872.6100 Food... DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6100 Anesthetic warmer. (a) Identification. An anesthetic warmer is an AC-powered device into which tubes containing anesthetic solution are intended to be...

21 CFR 872.6100 - Anesthetic warmer.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Anesthetic warmer. 872.6100 Section 872.6100 Food... DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6100 Anesthetic warmer. (a) Identification. An anesthetic warmer is an AC-powered device into which tubes containing anesthetic solution are intended to be...

21 CFR 872.6100 - Anesthetic warmer.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Anesthetic warmer. 872.6100 Section 872.6100 Food... DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6100 Anesthetic warmer. (a) Identification. An anesthetic warmer is an AC-powered device into which tubes containing anesthetic solution are intended to be...

Local anesthetics QX 572 and benzocaine act at separate sites on the batrachotoxin-activated sodium channel

PubMed Central

1981-01-01

We have studied the effect of local anesthetics QX 572, which is permanently charged, and benzocaine, which is neutral, on batrachotoxin- activated sodium channels in mouse neuroblastoma N18 cells. The dose- response curves for each drug suggest that QX 752 and benzocaine each act on a single class of binding sites. The dissociation constants are 3.15 X 10(-5) M for QX 572 and 2.65 X 10(-4) M for benzocaine. Equilibrium and kinetic experiments indicate that both drugs are competitive inhibitors of batrachotoxin. When benzocaine and QX 572 are present with batrachotoxin, they are much more effective at inhibiting Na+ flux than would be predicted by a one-site model. Our results indicate that QX 572 and benzocaine bind to separate sites, each of which interacts competitively with batrachotoxin. PMID:6267160

EFFECT OF RADIATION ON RESPONSE TO ANESTHETIC AGENTS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zauder, H.L.; Orkin, L.R.

1963-07-01

An attempt was made to determine if prior irradiation modified the response to anesthesia or if any anesthetic or anesthetics are associated with an abnormally high or low mortality, following irradiation. Swiss mice were irradiated by a conventional radiotherapy machine utilizing 250-kv x rays with 1- mm aluiminum and 0.5 mm copper filtration. The half-value layer was 1.5 mm of copper, and with a target-skin distance of 70 cm; the dose rate in air was 52 r/ min. A dose-response curve, relating mortality at 30 days to the amount of radiation delivered gave an LD/sub 5/ of 350 r, LD/submore » 25/ of 450 r, and LD/sub 95/ of 750 r. A chamber for the anesthetization of small animals with a known, reproducible concentration of anesthetic agent was designed providing for constant circulation of the gas mixtures, explosive or nonexplosive. Utilizing this apparatus, groups of mice were andesthetized with 6% divinyl ether, 6% diethyl ether, 1.5% halothane, 1.8% trichlorethylene, and 18% cyclopropane. With the latter, oxygen was added to the chamber in sufficient quandtity to provide a concentration of 20 to 25%. Pentobarbital (Nembutal) 30 mg/kg, thiopental sodium (Pentothal) 70 mg/kg, or meperidine hydrochloride (Demerol) 25 mg/kg was injected intraperitoneally into mice with and without prior x radiation. There was no mortality associated with these dosages in the control animals. All drugs were administered to the irradiated animals on the 1st to 28th day postirradiation. In mice irradiated with an LD/sub 5/ (350 r) and anesthetized subsequently with divinyl ether, diethyl ether, or halothane, an increase in the mortality over control values was observed. This increase was greatest following divinyl ether; its administration 7 or more days following irradiation resulted in the death of 10 to 30% of the animals during the 45-min period of anesthetization. After 350 r, meperidine and pentobarbital did not increase montality, but thiopental increased markedly the number

Slowing of the hippocampal θ-rhythm correlates with anesthetic-induced amnesia

PubMed Central

Perouansky, Misha; Rau, Vinuta; Ford, Tim; Oh, S. Irene; Perkins, Mark; Eger, Edmond I.; Pearce, Robert A.

2010-01-01

Background Temporary, antegrade amnesia is one of the core desirable endpoints of general anesthesia. Multiple lines of evidence support a role for the hippocampal θ-rhythm, a synchronized rhythmic oscillation of field potentials at 4–12 Hz, in memory formation. Previous studies have revealed a disruption of the θ-rhythm at surgical levels of anesthesia. We hypothesized that modulation of θ-rhythm would also occur at subhypnotic but amnestic concentrations. Therefore we examined the effect of three inhaled agents on properties of the θ-rhythm that are considered to be critical for the formation of hippocampus-dependent memories. Methods We studied the effects of halothane and nitrous oxide, two agents known to modulate different molecular targets (GABAergic vs. non-GABAergic, respectively), and isoflurane (both GABAergic and non-GABAergic targets), on fear-conditioned learning and θ-oscillations in freely behaving rats. Results All three anesthetics slowed θ-peak frequency in proportion to their inhibition of fear conditioning (by 1 Hz, 0.7 Hz and 0.5 Hz for 0.32% isoflurane, 60% N2O and 0.24% halothane). The anesthetics inconsistently affected other characteristics of θ-oscillations. Conclusions At sub-hypnotic amnestic concentrations, θ-oscillation frequency was the parameter most consistently affected by these three anesthetics. These results are consistent with the hypothesis that modulation of the θ-rhythm contributes to anesthetic-induced amnesia. PMID:21042201

Block of Inactivation-deficient Na+ Channels by Local Anesthetics in Stably Transfected Mammalian Cells

PubMed Central

Wang, Sho-Ya; Mitchell, Jane; Moczydlowski, Edward; Wang, Ging Kuo

2004-01-01

According to the classic modulated receptor hypothesis, local anesthetics (LAs) such as benzocaine and lidocaine bind preferentially to fast-inactivated Na+ channels with higher affinities. However, an alternative view suggests that activation of Na+ channels plays a crucial role in promoting high-affinity LA binding and that fast inactivation per se is not a prerequisite for LA preferential binding. We investigated the role of activation in LA action in inactivation-deficient rat muscle Na+ channels (rNav1.4-L435W/L437C/A438W) expressed in stably transfected Hek293 cells. The 50% inhibitory concentrations (IC50) for the open-channel block at +30 mV by lidocaine and benzocaine were 20.9 ± 3.3 μM (n = 5) and 81.7 ± 10.6 μM (n = 5), respectively; both were comparable to inactivated-channel affinities. In comparison, IC50 values for resting-channel block at −140 mV were >12-fold higher than those for open-channel block. With 300 μM benzocaine, rapid time-dependent block (τ ≈ 0.8 ms) of inactivation-deficient Na+ currents occurred at +30 mV, but such a rapid time-dependent block was not evident at −30 mV. The peak current at −30 mV, however, was reduced more severely than that at +30 mV. This phenomenon suggested that the LA block of intermediate closed states took place notably when channel activation was slow. Such closed-channel block also readily accounted for the LA-induced hyperpolarizing shift in the conventional steady-state inactivation measurement. Our data together illustrate that the Na+ channel activation pathway, including most, if not all, transient intermediate closed states and the final open state, promotes high-affinity LA binding. PMID:15545401

Local anesthesia for abdominoplasty, liposuction, and combined operations.

PubMed

Mottura, A A

1993-01-01

This article describes a procedure to perform abdominoplasty, liposuction, and combined operations under local anesthesia. With an anesthetic solution composed of 25 cc of 2% lidocaine, 25 cc of 0.5% bupivacaine, 1 cc of epinephrine or ornipresine, and 350 cc of saline solution, a satisfactory dilution with low concentration and lasting effects was obtained. After infiltration a large amount was lost in the incision, the dissection, and the resected dermofatty tissue. A small amount of anesthetic remained in the operated area to be metabolized by the liver. Low lidocaine levels were found in venous blood samples during surgery. This type of anesthesia is advised in minor, limited, and normal abdominoplasties in normal-sized patients, or major abdominoplasties in small patients. In liposuction procedures, it is possible to anesthetize the patient using the same procedure and operate in an equivalent area. As a high proportion of the infiltrated anesthesia was lost during the operation, a similar amount could be used to infiltrate and operate other areas so that an abdominoplasty might be combined with liposuction or mastoplasty. We have experience with 25 abdominoplasties and 21 liposuctions performed under local anesthesia. There were no complications related to local anesthesia and no one had unpleasant memories of intraoperative events.

Scientometrics of anesthetic drugs and their techniques of administration, 1984–2013

PubMed Central

Vlassakov, Kamen V; Kissin, Igor

2014-01-01

The aim of this study was to assess progress in the field of anesthetic drugs over the past 30 years using scientometric indices: popularity indices (general and specific), representing the proportion of articles on a drug relative to all articles in the field of anesthetics (general index) or the subfield of a specific class of anesthetics (specific index); index of change, representing the degree of growth in publications on a topic from one period to the next; index of expectations, representing the ratio of the number of articles on a topic in the top 20 journals relative to the number of articles in all (>5,000) biomedical journals covered by PubMed; and index of ultimate success, representing a publication outcome when a new drug takes the place of a common drug previously used for the same purpose. Publications on 58 topics were assessed during six 5-year periods from 1984 to 2013. Our analysis showed that during 2009–2013, out of seven anesthetics with a high general popularity index (≥2.0), only two were introduced after 1980, ie, the inhaled anesthetic sevoflurane and the local anesthetic ropivacaine; however, only sevoflurane had a high index of expectations (12.1). Among anesthetic adjuncts, in 2009–2013, only one agent, sugammadex, had both an extremely high index of change (>100) and a high index of expectations (25.0), reflecting the novelty of its mechanism of action. The index of ultimate success was positive with three anesthetics, ie, lidocaine, isoflurane, and propofol, all of which were introduced much longer than 30 years ago. For the past 30 years, there were no new anesthetics that have produced changes in scientometric indices indicating real progress. PMID:25525336

Ketamine changes the local resting-state functional properties of anesthetized-monkey brain.

PubMed

Rao, Jia-Sheng; Liu, Zuxiang; Zhao, Can; Wei, Rui-Han; Zhao, Wen; Tian, Peng-Yu; Zhou, Xia; Yang, Zhao-Yang; Li, Xiao-Guang

2017-11-01

Ketamine is a well-known anesthetic. 'Recreational' use of ketamine common induces psychosis-like symptoms and cognitive impairments. The acute and chronic effects of ketamine on relevant brain circuits have been studied, but the effects of single-dose ketamine administration on the local resting-state functional properties of the brain remain unknown. In this study, we aimed to assess the effects of single-dose ketamine administration on the brain local intrinsic properties. We used resting-state functional magnetic resonance imaging (rs-fMRI) to explore the ketamine-induced alterations of brain intrinsic properties. Seven adult rhesus monkeys were imaged with rs-fMRI to examine the fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) in the brain before and after ketamine injection. Paired comparisons were used to detect the significantly altered regions. Results showed that the fALFF of the prefrontal cortex (p=0.046), caudate nucleus (left side, p=0.018; right side, p=0.025), and putamen (p=0.020) in post-injection stage significantly increased compared with those in pre-injection period. The ReHo of nucleus accumbens (p=0.049), caudate nucleus (p=0.037), and hippocampus (p=0.025) increased after ketamine injection, but that of prefrontal cortex decreased (p<0.05). These findings demonstrated that single-dose ketamine administration can change the regional intensity and synchronism of brain activity, thereby providing evidence of ketamine-induced abnormal resting-state functional properties in primates. This evidence may help further elucidate the effects of ketamine on the cerebral resting status. Copyright © 2017. Published by Elsevier Inc.

Investigation of local anesthetic and antimycobacterial activity of Ottonia martiana Miq. (Piperaceae).

PubMed

Cunico, Miriam M; Trebien, Herbert A; Galetti, Fábio C; Miguel, Obdulio G; Miguel, Marilis D; Auer, Celso G; Silva, Célio L; de Souza, Ana Olívia

2015-01-01

Ottonia martiana is a plant popularly known in Brazil by the use for toothache. Ethanolic extract (EE), hexane fraction (HF), dichloromethane fraction (DF) and piperovatine obtained from O. martiana were assayed in vitro and in vivo. The acute toxicity of EE was determined, and LD50 values of 164.5 and 65.0 mg/kg by the oral and intraperitoneal routes, respectively, indicated a high toxicity for EE in vivo, explaining its popular use by topical administration only. A local anesthetic-like effect of EE and its fractions was observed in experimental models using pain induction, and such effect involved an analgesic action. The antimycobacterial activity of EE, HF, DF and piperovatine was evaluated against Mycobacterium tuberculosis H37Rv ATCC 27924. EE, HF, DF, and piperovatine showed a potential antimycobacterial effect with MICs of 16.0, 62.0, 62.0 and 8.0 μg/mL, respectively. Piperovatine was more effective than the EE or the other fractions. The selectivity index (SI=IC50/MIC) values calculated for EE, HF, DF and piperovatine based on the MICs and the cytotoxicity against J774 macrophages (IC50 by MTT assay) revealed values of 6.43, 2.34, 1.5 and 9.66, respectively.

Evaluation of anesthetic technique on surgical site infections (SSIs) at a single institution.

PubMed

Curry, Craig S; Smith, Kahsi A; Allyn, John W

2014-12-01

To determine whether the previously published relationship between anesthetic technique and rate of surgical site infections (SSIs) was influenced by institution specific effects. Retrospective Review of Quality Assurance and Hospital Epidemiology databases. Metropolitan medical center. The records of 7,751 patients who underwent knee or hip joint replacement from 2004 to 2010 were analyzed. Data regarding anesthetic technique, age, ASA status, gender, postoperative temperature, duration of anesthesia and type of surgery were from the department of anesthesiology quality assurance database and SSI cases were identified from the department of epidemiology database. The impact of anesthetic technique and other variables was assessed using bivariate and multivariate techniques. There was no association of anesthetic technique on the rate of SSI. Duration of anesthesia and ASA status were associated with effects on the rate of SSI. The impact of anesthetic technique on SSI following hip and knee replacement surgery may be site specific and using locally gathered quality data may assist in assessing specific institutional impact. Copyright © 2014 Elsevier Inc. All rights reserved.

Anesthetic Agents and Neuronal Autophagy. What We Know and What We Don't.

PubMed

Xu, Lili; Shen, Jianjun; McQuillan, Patrick M; Hu, Zhiyong

2018-01-01

Ethanol is known to have both γ-Aminobutyric acid agonist and Nmethyl- D-aspartate antagonist characteristics similar to commonly used volatile anesthetic agents. Recent evidence demonstrates that autophagy can reduce the development of ethanol induced neurotoxicity. Recent studies have found that general anesthesia can cause longterm impairment of both mitochondrial morphogenesis and synaptic transmission in the developing rat brain, both of which are accompanied by enhanced autophagy activity. Autophagy may play an important role in general anesthetic mediated neurotoxicity. This review outlines the role of autophagy in the development of anesthetic related neurotoxicity and includes an explanation of the role of autophagy in neuronal cell survival and death, the relationship between anesthetic agents and neuronal autophagy, possible molecular and cellular mechanisms underlying general anesthetic agent induced activation of neuronal autophagy in the developing brain, and potential therapeutic approaches aimed at modulating autophagic pathways. In a time- and concentration-dependent pattern, general anesthetic agents can disrupt intracellular calcium homeostasis which enhances both autophagy and apoptosis activation. The degree of neural cell injury may be ultimately determined by the interplay between autophagy and apoptosis. It appears likely that the increase in calcium flux associated with some anesthetic agents disrupts lysosomal function. This results in an over-activation of endosomal- lysosomal trafficking causing mitochondrial damage, reactive oxygen species upregulation, and lipid peroxidation. Autophagy may play a role in the development of anesthetic related neurotoxicity. Understanding this may lead to strategies or therapies aimed at preventing or ameliorating general anesthetic agent mediated neurotoxicity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

[Assessment of occupational exposure of medical personnel to inhalatory anesthetics in Poland].

PubMed

Kucharska, Małgorzata; Wesołowski, Wiktor

2014-01-01

Despite common use of inhalatory anesthetics, such as nitrous oxide (N2O), halothane, sevoflurane, and the like, occupational exposure to these substances in operating theatres was not monitored in Poland until 2006. The situation changed when maximum admissible concentration (MAC) values for anesthetics used in Poland were established in 2005 for N2O, and in 2007 for sevoflurane, desflurane and isoflurane. The aim of this work was to assess occupational exposure in operating rooms on the basis of reliable and uniform analytical procedures. The method for the determination of all anesthetics used in Poland, i.e. nitrous oxide, sevoflurane, isoflurane, desflurane, and halothane, was developed and validated. The measurements were performed in 2006-2010 in 31 hospitals countrywide. The study covered 117 operating rooms; air samples were collected from the breathing zone of 146 anesthesiologists, and 154 nurses, mostly anaesthetic. The measurements were carried out during various surgical operations, mostly on adult patients but also in hospitals for children. Time weighted average concentrations of the anesthetics varied considerably, and the greatest differences were noted for N2O (0.1-1438.5 mg/m3); 40% of the results exceeded the MAC value. Only 3% of halothane, and 2% of sevoflurane concentrations exceeded the respective MAC values. Working in operating theatres is dangerous to the health of the operating staff. The coefficient of combined exposure to anesthesiologists under study exceeded the admissible value in 130 cases, which makes over 40% of the whole study population. Most of the excessive exposure values were noted for nitrous oxide.

Lumbar segmental nerve blocks with local anesthetics, pain relief, and motor function: a prospective double-blind study between lidocaine and ropivacaine.

PubMed

Wolff, André P; Wilder Smith, Oliver H G; Crul, Ben J P; van de Heijden, Marc P; Groen, Gerbrand J

2004-08-01

Selective segmental nerve blocks with local anesthetics are applied for diagnostic purposes in patients with chronic back pain to determine the segmental level of the pain. We performed this study to establish myotomal motor effects after L4 spinal nerve blocks by lidocaine and ropivacaine and to evaluate the relationship with pain. Therefore, 20 patients, of which 19 finished the complete protocol, with chronic lumbosacral radicular pain without neurological deficits underwent segmental nerve blocks at L4 with both lidocaine and ropivacaine. Pain intensity scores (verbal numeric rating scale; VNRS) and the maximum voluntary muscle force (MVMF; using a dynamometer expressed in newtons) of the tibialis anterior and quadriceps femoris muscles were measured on the painful side and on the control side. The median VNRS decrease was 4.0 (P < 0.00001; Wilcoxon's signed rank test), without significant differences between ropivacaine and lidocaine (Mann-Whitney U-test). A difference in effect on MVMF was found for affected versus control side (P = 0.016; Tukey test). Multiple regression revealed a significant negative correlation for change in VNRS score versus change in median MVMF (Spearman R = -0.48: P = 0.00001). This study demonstrates that in patients with unilateral chronic low back pain radiating to the leg, pain reduction induced by local anesthetic segmental nerve (L4) block is associated with increased quadriceps femoris and tibialis anterior MVMF, without differences for lidocaine and ropivacaine.

The efficacy of an elevated concentration of lidocaine HCl in impacted lower third molar surgery.

PubMed

Ping, Bushara; Kiattavorncharoen, Sirichai; Saengsirinavin, Chavengkiat; Im, Puthavy; Durward, Callum; Wongsirichat, Natthamet

2015-06-01

There have been few studies on the effect of an elevated concentration of lidocaine hydrochloride in the surgical removal of an impacted lower third molar. This study aimed to examine the efficacy of 4% lidocaine along with 1:100,000 epinephrine compared to 2% lidocaine along with 1:100,000 epinephrine as inferior alveolar nerve block for the removal of an impacted lower third molar. This single-blind study involved 31 healthy patients (mean age: 23 y; range: 19-33 y) with symmetrically impacted lower third molars as observed on panoramic radiographs. Volunteers required 2 surgical interventions by the same surgeon with a 3-week washout period. The volunteers were assigned either 4% lidocaine with 1:100,000 epinephrine or 2% lidocaine with 1:100,000 epinephrine as local anesthetic during each operation. We recorded the time of administration, need for additional anesthetic administration, total volume of anesthetic used. We found that the patient's preference for either of the 2 types of local anesthetic were significantly different (P < 0.05). However, the extent of pulpal anesthesia, surgical duration, and duration of soft tissue anesthesia were not significantly different. Our study suggested that inferior alveolar nerve block using 4% lidocaine HCl with 1:100,000 epinephrine as a local anesthetic was clinically more effective than that using 2% lidocaine HCl with 1:100,000 epinephrine; the surgical duration was not affected, and no clinically adverse effects were encountered.

Pain associated with local anesthetic injection in eyelid procedures: Comparison of microprocessor-controlled versus traditional syringe techniques.

PubMed

Lee, Edward W; Tucker, Nancy A

2007-01-01

To evaluate the pain associated with local infiltration of the eyelid, using a microprocessor-controlled delivery system (CompuMed, using the Wand), as compared with traditional manual syringe infiltration technique. A randomized clinical trial of 30 patients undergoing minor eyelid surgical procedures was performed. Fifteen patients were injected by use of the CompuMed system and 15 patients were injected by the traditional manual syringe technique. The severity of pain was recorded from each patient by using a visual analog scale (0 to 10). The duration of pain experienced by the patient was also recorded. The mean pain level reported was 1.5 in the Wand group and 3.2 in the syringe group (p < 0.01). The mean duration of pain experienced was 1.5 seconds in the Wand group and 34 seconds in the syringe group (p < 0.01). The Wand was effective at significantly reducing the pain associated with local anesthetic infiltration in minor eyelid surgical procedures. Patients appear to feel pain from the initial needle stick but not during the actual injection.

Drosophila social clustering is disrupted by anesthetics and in narrow abdomen ion channel mutants.

PubMed

Burg, E D; Langan, S T; Nash, H A

2013-04-01

Members of many species tend to congregate, a behavioral strategy known as local enhancement. Selective advantages of local enhancement range from efficient use of resources to defense from predators. While previous studies have examined many types of social behavior in fruit flies, few have specifically investigated local enhancement. Resource-independent local enhancement (RILE) has recently been described in the fruit fly using a measure called social space index (SSI), although the neural mechanisms remain unknown. Here, we analyze RILE of Drosophila under conditions that allow us to elucidate its neural mechanisms. We have investigated the effects of general volatile anesthetics, compounds that compromise higher order functioning of the type typically required for responding to social cues. We exposed Canton-S flies to non-immobilizing concentrations of halothane and found that flies had a significantly decreased SSI compared with flies tested in air. Narrow abdomen (na) mutants, which display altered responses to anesthetics in numerous behavioral assays, also have a significantly reduced SSI, an effect that was fully reversed by restoring expression of na by driving a UAS-NA rescue construct with NA-GAL4. We found that na expression in cholinergic neurons fully rescued the behavioral defect, whereas expression of na in glutamatergic neurons did so only partially. Our results also suggest a role for na expression in the mushroom bodies (MBs), as suppressing na expression in the MBs of NA-GAL4 rescue flies diminishes SSI. Our data indicate that RILE, a simple behavioral strategy, requires complex neural processing. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

Molecular interactions between general anesthetics and the 5HT2B receptor.

PubMed

Matsunaga, Felipe; Gao, Lu; Huang, Xi-Ping; Saven, Jeffery G; Roth, Bryan L; Liu, Renyu

2015-01-01

Serotonin modulates many processes through a family of seven serotonin receptors. However, no studies have screened for interactions between general anesthetics currently in clinical use and serotonergic G-protein-coupled receptors (GPCRs). Given that both intravenous and inhalational anesthetics have been shown to target other classes of GPCRs, we hypothesized that general anesthetics might interact directly with some serotonin receptors and thus modify their function. Radioligand binding assays were performed to screen serotonin receptors for interactions with propofol and isoflurane as well as for affinity determinations. Docking calculations using the crystal structure of 5-HT2B were performed to computationally confirm the binding assay results and locate anesthetic binding sites. The 5-HT2B class of receptors interacted significantly with both propofol and isoflurane in the primary screen. The affinities for isoflurane and propofol were determined to be 7.78 and .95 μM, respectively, which were at or below the clinical concentrations for both anesthetics. The estimated free energy derived from docking calculations for propofol (-6.70 kcal/mol) and isoflurane (-5.10 kcal/mol) correlated with affinities from the binding assay. The anesthetics were predicted to dock at a pharmacologically relevant binding site of 5HT2B. The molecular interactions between propofol and isoflurane with the 5-HT2B class of receptors were discovered and characterized. This finding implicates the serotonergic GPCRs as potential anesthetic targets.

Bioadhesive films containing benzocaine: correlation between in vitro permeation and in vivo local anesthetic effect.

PubMed

de Araujo, Daniele Ribeiro; Padula, Cristina; Cereda, Cíntia Maria Saia; Tófoli, Giovana Radomille; Brito, Rui Barbosa; de Paula, Eneida; Nicoli, Sara; Santi, Patrizia

2010-08-01

The aim of this work was to develop anesthetic bioadhesive films containing benzocaine and study their in vitro skin permeation and in vivo performance, in comparison with commercial formulations. Films containing 3% and 5% w/w of benzocaine were prepared and characterized by weight, drug content, thickness and morphology. In vitro permeation assays were performed in vertical diffusion cells using full-thickness pig ear skin as barrier. Intensity and duration of analgesia were evaluated in rats by tail-flick test, and skin histological analysis was carried out. Tail-flick test showed that the duration of benzocaine-induced analgesia was significantly prolonged with the films compared to commercial creams, in agreement with the higher in vitro permeation. Histological analysis of the rat tail skin did not reveal morphological tissue changes nor cell infiltration signs after application of the commercial creams or films. Results from our study indicate that the films developed in this work can be considered as innovative dermal/transdermal therapeutic systems for benzocaine local delivery.

Effects of Volatile Aromatic Anesthetics on Voltage-Gated Na+ Channels Expressed in Xenopus Oocytes

PubMed Central

Horishita, Takafumi; Eger, Edmond I; Harris, R. Adron

2008-01-01

Background Many inhaled anesthetics inhibit voltage-gated sodium channels at clinically relevant concentrations, and suppression of neurotransmitter release by these agents results, at least partly, from decreased presynaptic sodium channel activity. Volatile aromatic anesthetics can inhibit N-methyl-D-aspartate (NMDA) receptor function and enhance γ-amino butyric acid A (GABAA) receptor function, but these effects depend strongly on the chemical properties of the aromatic ompounds. The present study tested whether diverse aromatic anesthetics consistently inhibit sodium channel function. Methods We studied the effect of eight aromatic anesthetics on Nav1.2 sodium channels with β1 subunits, using whole-cell, two-electrode voltage-clamp techniques in Xenopus oocytes. Results All aromatic anesthetics inhibited INa (sodium currents) at a holding potential which produce half-maximal current (V1/2) (partial depolarization); inhibition was modest with 1,3,5-trifluorobenzene (8 ± 2%), pentafluorobenzene (13 ± 2%), and hexafluorobenzene (13 ± 2%), but greater with benzene (37 ± 2%), fluorobenzene (39 ± 2%), 1,2-difluorobenzene (48 ± 2%), 1,4-difluorobenzene (31 ± 3%), and 1,2,4-trifluorobenzene (33 ± 1%). Such dichotomous effects were noted by others for NMDA and GABAA receptors. Parallel, but much smaller inhibition, was found for INa at a holding potential which produced near maximal current (−90 mV) (VH-90), and hexafluorobenzene caused small (6 ± 1%) potentiation of this current. These changes in sodium channel function were correlated with effectiveness for inhibiting NMDA receptors, with lipid solubility of the compounds, with molecular volume, and with cation-π interactions. Conclusion Aromatic compounds vary in their actions on the kinetics of sodium channel gating and this may underlie their variable inhibition. The range of inhibition produced by MAC concentrations of inhaled anesthetics indicates that sodium channel inhibition may underlie the

Heart Rate Effects of Intraosseous Injections Using Slow and Fast Rates of Anesthetic Solution Deposition

PubMed Central

Susi, Louis; Reader, Al; Nusstein, John; Beck, Mike; Weaver, Joel; Drum, Melissa

2008-01-01

The authors, using a crossover design, randomly administered, in a single-blind manner, 3 primary intraosseous injections to 61 subjects using: the Wand local anesthetic system at a deposition rate of 45 seconds (fast injection); the Wand local anesthetic system at a deposition rate of 4 minutes and 45 seconds (slow injection); a conventional syringe injection at a deposition rate of 4 minutes and 45 seconds (slow injection), in 3 separate appointments spaced at least 3 weeks apart. A pulse oximeter measured heart rate (pulse). The results demonstrated the mean maximum heart rate was statistically higher with the fast intraosseous injection (average 21 to 28 beats/min increase) than either of the 2 slow intraosseous injections (average 10 to 12 beats/min increase). There was no statistically significant difference between the 2 slow injections. We concluded that an intraosseous injection of 1.4 mL of 2% lidocaine with 1 : 100,000 epinephrine with the Wand at a 45-second rate of anesthetic deposition resulted in a significantly higher heart rate when compared with a 4-minute and 45-second anesthetic solution deposition using either the Wand or traditional syringe. PMID:18327970

Heart rate effects of intraosseous injections using slow and fast rates of anesthetic solution deposition.

PubMed

Susi, Louis; Reader, Al; Nusstein, John; Beck, Mike; Weaver, Joel; Drum, Melissa

2008-01-01

The authors, using a crossover design, randomly administered, in a single-blind manner, 3 primary intraosseous injections to 61 subjects using: the Wand local anesthetic system at a deposition rate of 45 seconds (fast injection); the Wand local anesthetic system at a deposition rate of 4 minutes and 45 seconds (slow injection); a conventional syringe injection at a deposition rate of 4 minutes and 45 seconds (slow injection), in 3 separate appointments spaced at least 3 weeks apart. A pulse oximeter measured heart rate (pulse). The results demonstrated the mean maximum heart rate was statistically higher with the fast intraosseous injection (average 21 to 28 beats/min increase) than either of the 2 slow intraosseous injections (average 10 to 12 beats/min increase). There was no statistically significant difference between the 2 slow injections. We concluded that an intraosseous injection of 1.4 mL of 2% lidocaine with 1 : 100,000 epinephrine with the Wand at a 45-second rate of anesthetic deposition resulted in a significantly higher heart rate when compared with a 4-minute and 45-second anesthetic solution deposition using either the Wand or traditional syringe.

TASK channel deletion reduces sensitivity to local anesthetic-induced seizures

PubMed Central

Du, Guizhi; Chen, Xiangdong; Todorovic, Marko S.; Shu, Shaofang; Kapur, Jaideep; Bayliss, Douglas A.

2011-01-01

Background Local anesthetics (LAs) are typically used for regional anesthesia but can be given systemically to mitigate postoperative pain, supplement general anesthesia or prevent cardiac arrhythmias. However, systemic application or inadvertent intravenous injection can be associated with substantial toxicity, including seizure induction. The molecular basis for this toxic action remains unclear. Methods We characterized effects of different LAs on homomeric and heteromeric K+ channels containing TASK-1 (K2P3.1, KCNK3) and TASK-3 (K2P9.1, KCNK9) subunits in a mammalian expression system. In addition, we used TASK-1/TASK-3 knockout mice to test the possibility that TASK channels contribute to LA-evoked seizures. Results LAs inhibited homomeric and heteromeric TASK channels in a range relevant for seizure induction; channels containing TASK-1 subunits were most sensitive and IC50 values indicated a rank order potency of bupivacaine > ropivacaine ⟫ lidocaine. LAs induced tonic-clonic seizures in mice with the same rank order potency, but higher LA doses were required to evoke seizures in TASK knockout mice. For bupivacaine, which produced the longest seizure times, seizure duration was significantly shorter in TASK knockout mice; bupivacaine-induced seizures were associated with an increase in electroencephalogram power at frequencies <5 Hz in both wild type and TASK knockout mice. Conclusions These data suggest that increased neuronal excitability associated with TASK channel inhibition by LAs contributes to seizure induction. Since all LAs were capable of evoking seizures in TASK channel deleted mice, albeit at higher doses, the results imply that other molecular targets must also be involved in this toxic action. PMID:21946151

Updates of Topical and Local Anesthesia Agents.

PubMed

Boyce, Ricardo A; Kirpalani, Tarun; Mohan, Naveen

2016-04-01

As described in this article, there are many advances in topical and local anesthesia. Topical and local anesthetics have played a great role in dentistry in alleviating the fears of patients, eliminating pain, and providing pain control. Many invasive procedures would not be performed without the use and advances of topical/local anesthetics. The modern-day dentist has the responsibility of knowing the variety of products on the market and should have at least references to access before, during, and after treatment. This practice ensures proper care with topical and local anesthetics for the masses of patients entering dental offices worldwide. Copyright © 2016 Elsevier Inc. All rights reserved.

Economic considerations in the use of inhaled anesthetic agents.

PubMed

Golembiewski, Julie

2010-04-15

To describe the components of and factors contributing to the costs of inhaled anesthesia, basis for quantifying and comparing these costs, and practical strategies for performing pharmacoeconomic analyses and reducing the costs of inhaled anesthetic agents. Inhaled anesthesia can be costly, and some of the variable costs, including fresh gas flow rates and vaporizer settings, are potential targets for cost savings. The use of a low fresh gas flow rate maximizes rebreathing of exhaled anesthetic gas and is less costly than a high flow rate, but it provides less control of the level of anesthesia. The minimum alveolar concentration (MAC) hour is a measure that can be used to compare the cost of inhaled anesthetic agents at various fresh gas flow rates. Anesthesia records provide a sense of patterns of inhaled anesthetic agent use, but the amount of detail can be limited. Cost savings have resulted from efforts to reduce the direct costs of inhaled anesthetic agents, but reductions in indirect costs through shortened times to patient recovery and discharge following the judicious use of these agents are more difficult to demonstrate. The patient case mix, fresh gas flow rates typically used during inhaled anesthesia, availability and location of vaporizers, and anesthesia care provider preferences and practices should be taken into consideration in pharmacoeconomic evaluations and recommendations for controlling the costs of inhaled anesthesia. Understanding factors that contribute to the costs of inhaled anesthesia and considering those factors in pharmacoeconomic analyses and recommendations for use of these agents can result in cost savings.

Tricaine (MS-222) is a safe anesthetic compound compared to benzocaine and pentobarbital to induce anesthesia in leopard frogs (Rana pipiens).

PubMed

Cakir, Yavuz; Strauch, Stephen M

2005-01-01

Tricaine (MS-222) is used commonly for sedation, immobilization, and anesthesia of poikilothermic animals. The anesthetic efficacy of different concentrations of MS-222 was compared to benzocaine and pentobarbital on the physiological changes, heart rate and ECG (electrocardiogram) parameters in the leopard frog, Rana pipiens. Loss of righting reflex (RR), loss of pain response (NR = nociceptor response) and recovery time were measured. Heart rate and ECG parameters were also tested before and during anesthesia. The time to loss of RR and NR decreased while recovery time markedly increased with the increasing concentration of MS-222. Benzocaine at 200 mg/l induced a rapid anesthesia, but all frogs needed resuscitation. Pentobarbital at 300 mg/l induced a slow anesthesia, however, all of the frogs also needed resuscitation. All anesthetics at the mentioned concentrations decreased heart rate significantly as well as altered the ECG parameters. All anesthetics prolonged the Q-T interval, and MS-222 at 800 mg/l and benzocaine at 200 mg/l were the most effective anesthetic concentrations in increasing the Q-T interval. Frogs anesthetized by benzocaine and pentobarbital and high concentrations of MS-222 required resuscitation due to hypoxia. Pentobarbital and benzocaine seem to be very effective compounds, but their safety margins are narrow because of ventilatory failure. Therefore, MS-222 at a concentration of 200 mg/l or less is highly recommended for leopard frogs because prolonged recovery, high mortality rate and significant ECG changes are observed with higher concentrations of MS-222.

Respiratory reflexes in spontaneously breathing anesthetized dogs in response to nasal administration of sevoflurane, isoflurane, or halothane.

PubMed

Mutoh, T; Kanamaru, A; Suzuki, H; Tsubone, H; Nishimura, R; Sasaki, N

2001-03-01

To characterize respiratory reflexes elicited by nasal administration of sevoflurane (Sevo), isoflurane (Iso), or halothane (Hal) in anesthetized dogs. 8 healthy Beagles. A permanent tracheostomy was created in each dog. Two to 3 weeks later, dogs were anesthetized by IV administration of thiopental and alpha-chloralose. Nasal passages were isolated such that inhalant anesthetics could be administered to the nasal passages while the dogs were breathing 100% O2 via the tracheostomy. Respiratory reflexes in response to administration of each anesthetic at 1.2 and 2.4 times the minimum alveolar concentration (MAC) and the full vaporizer setting (5%) were recorded. Reflexes in response to administration of 5% of each anesthetic also were recorded following administration of lidocaine to the nasal passages. Nasal administration of Sevo, Iso, and Hal induced an immediate ventilatory response characterized by a dose-dependent increase in expiratory time and a resulting decrease in expired volume per unit of time. All anesthetics had a significant effect, but for Sevo, the changes were smaller in magnitude. Responses to administration of each anesthetic were attenuated by administration of lidocaine to the nasal passages. Nasal administration of Sevo at concentrations generally used for mask induction of anesthesia induced milder reflex inhibition of breathing, presumably via afferent neurons in the nasal passages, than that of Iso or Hal. Respiratory reflexes attributable to stimulation of the nasal passages may contribute to speed of onset and could promote a smoother induction with Sevo, compared with Iso or Hal.

[Comparison of waste anesthetic gases in operating rooms with or without an scavenging system in a Brazilian University Hospital].

PubMed

Braz, Leandro Gobbo; Braz, José Reinaldo Cerqueira; Cavalcante, Guilherme Aparecido Silva; Souza, Kátina Meneghetti; Lucio, Lorena Mendes de Carvalho; Braz, Mariana Gobbo

Occupational exposure to waste anesthetic gases in operating room (OR) without active scavenging system has been associated with adverse health effects. Thus, this study aimed to compare the trace concentrations of the inhaled anesthetics isoflurane and sevoflurane in OR with and without central scavenging system. Waste concentrations of isoflurane and sevoflurane were measured by infrared analyzer at different locations (near the respiratory area of the assistant nurse and anesthesiologist and near the anesthesia station) and at two times (30 and 120minutes after the start of surgery) in both OR types. All isoflurane and sevoflurane concentrations in unscavenged OR were higher than the US recommended limit (2 parts per million), regardless of the location and time evaluated. In scavenged OR, the average concentrations of isoflurane were within the limit of exposure, except for the measurements near the anesthesia station, regardless of the measurement times. For sevoflurane, concentrations exceeded the limit value at all measurement locations and at both times. The exposure to both anesthetics exceeded the international limit in unscavenged OR. In scavenged OR, the concentrations of sevoflurane, and to a lesser extent those of isoflurane, exceeded the recommended limit value. Thus, the OR scavenging system analyzed in the present study decreased the anesthetic concentrations, although not to the internationally recommended values. Copyright © 2017 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

A membrane-embedded pathway delivers general anesthetics to two interacting binding sites in the Gloeobacter violaceus ion channel.

PubMed

Arcario, Mark J; Mayne, Christopher G; Tajkhorshid, Emad

2017-06-09

General anesthetics exert their effects on the central nervous system by acting on ion channels, most notably pentameric ligand-gated ion channels. Although numerous studies have focused on pentameric ligand-gated ion channels, the details of anesthetic binding and channel modulation are still debated. A better understanding of the anesthetic mechanism of action is necessary for the development of safer and more efficacious drugs. Herein, we present a computational study identifying two anesthetic binding sites in the transmembrane domain of the Gloeobacter violaceus ligand-gated ion channel (GLIC) channel, characterize the putative binding pathway, and observe structural changes associated with channel function. Molecular simulations of desflurane reveal a binding pathway to GLIC via a membrane-embedded tunnel using an intrasubunit protein lumen as the conduit, an observation that explains the Meyer-Overton hypothesis, or why the lipophilicity of an anesthetic and its potency are generally proportional. Moreover, employing high concentrations of ligand led to the identification of a second transmembrane site (TM2) that inhibits dissociation of anesthetic from the TM1 site and is consistent with the high concentrations of anesthetics required to achieve clinical effects. Finally, asymmetric binding patterns of anesthetic to the channel were found to promote an iris-like conformational change that constricts and dehydrates the ion pore, creating a 13.5 kcal/mol barrier to ion translocation. Together with previous studies, the simulations presented herein demonstrate a novel anesthetic binding site in GLIC that is accessed through a membrane-embedded tunnel and interacts with a previously known site, resulting in conformational changes that produce a non-conductive state of the channel. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Comparative cardiovascular effects of four fishery anesthetics in spinally transected rainbow trout, oncorhynchus mykiss

USGS Publications Warehouse

Fredricks, K.T.; Gingerich, W.H.; Fater, D.C.

1993-01-01

1. We compared the effects of four anesthetics on heart rate, dorsal and ventral aortic blood pressure, and electrocardiograms of rainbow trout (Oncorhynchus mykiss).2. Exposure to the local anesthetics tricaine methanesulfonate (MS-222) and benzocaine hydrochloride (BZH) produced minimal cardiovascular alterations. Mean dorsal aortic pressure (DAP) decreased during exposure to MS-222, and mean DAP and mean ventral aortic pressure (VAP) increased 15% during recovery from BZH.3. Exposure to the general anesthetic 2-phenoxyethanol (2-PE) or the hypnotic agent etomidate (ET) dramatically decreased heart rate and blood pressures and altered EKG patterns.4. During recovery, VAP and DAP increased above baseline for an extended period. Heart rate and EKG patterns rapidly returned to normal.

Comparison of the efficacy and safety of 2% lidocaine HCl with different epinephrine concentration for local anesthesia in participants undergoing surgical extraction of impacted mandibular third molars: A multicenter, randomized, double-blind, crossover, phase IV trial.

PubMed

Karm, Myong-Hwan; Park, Fiona Daye; Kang, Moonkyu; Kim, Hyun Jeong; Kang, Jeong Wan; Kim, Seungoh; Kim, Yong-Deok; Kim, Cheul-Hong; Seo, Kwang-Suk; Kwon, Kyung-Hwan; Kim, Chul-Hwan; Lee, Jung-Woo; Hong, Sung-Woon; Lim, Mi Hyoung; Nam, Seung Kwan; Cho, Jae Min

2017-05-01

The most commonly impacted tooth is the third molar. An impacted third molar can ultimately cause acute pain, infection, tumors, cysts, caries, periodontal disease, and loss of adjacent teeth. Local anesthesia is employed for removing the third molar. This study aimed to evaluate the efficacy and safety of 2% lidocaine with 1:80,000 or 1:200,000 epinephrine for surgical extraction of bilateral impacted mandibular third molars. Sixty-five healthy participants underwent surgical extraction of bilateral impacted mandibular third molars in 2 separate visits while under local anesthesia with 2% lidocaine with different epinephrine concentration (1:80,000 or 1:200,000) in a double-blind, randomized, crossover trial. Visual analog scale pain scores obtained immediately after surgical extraction were primarily evaluated for the 2 groups receiving different epinephrine concentrations. Visual analog scale pain scores were obtained 2, 4, and 6 hours after administering an anesthetic. Onset and duration of analgesia, onset of pain, intraoperative bleeding, operator's and participant's overall satisfaction, drug dosage, and hemodynamic parameters were evaluated for the 2 groups. There were no statistically significant differences between the 2 groups in any measurements except hemodynamic factors (P >.05). Changes in systolic blood pressure and heart rate following anesthetic administration were significantly greater in the group receiving 1:80,000 epinephrine than in that receiving 1:200,000 epinephrine (P ≤.01). The difference in epinephrine concentration between 1:80,000 and 1:200,000 in 2% lidocaine liquid does not affect the medical efficacy of the anesthetic. Furthermore, 2% lidocaine with 1:200,000 epinephrine has better safety with regard to hemodynamic parameters than 2% lidocaine with 1:80,000 epinephrine. Therefore, we suggest using 2% lidocaine with 1:200,000 epinephrine rather than 2% lidocaine with 1:80,000 epinephrine for surgical extraction of impacted

Comparative Assessment of the Effects of Three Local Anesthetics: Lidocaine, Prilocaine, and Mepivacaine on Blood Pressure Changes in Patients with Controlled Hypertension.

PubMed

Hashemi, Seyyed Hamed Jalalian; Ladez, Shamsodin Rigi; Moghadam, Somaye Ansari

2016-10-01

Given large number of patients with hypertension attending dental clinics and the profound effects of local anesthetics containing vasoconstrictors, this study aimed to compare the effects of lidocaine 2% + epinephrine, prilocaine 3% + felypressin0.03, and mepivacaine 3% on blood pressure changes. The current study was carried out from May 2014 to February 2015.Patients with controlled hypertension (systolic blood pressure<159.94 mmHg before the injection) who attended Zahedan dental school (Zahedan , Iran) for the extraction of a mandibular tooth were selected and randomly allocated to three groups of 20. Groups 1-3 received lidocaine 2% + epinephrine, prilocaine 3% + felypressin 0.03 units, and mepivacaine3%, respectively. Patients were only included if they were injected with a maximum of two 1.8 ml cartridges (3.6 ml) for tooth extraction (maximum epinephrine dose of 0.04 mg was maintained in systemic patients).The collected data were analyzed using the analysis of variance (ANOVA) in SPSS 19.0. (SPSS Inc., Chicago, IL, USA)RESULTS: No significant differences were observed between the systolic and diastolic blood pressure of the three groups. The three evaluated local anesthetic solutions had similar effects in patients with controlled hypertension. While no significant changes in blood pressure were observed in three groups, all dental procedures on the mentioned group of patients have to be performed under careful monitoring and aspiration. Moreover, the maximum epinephrine dose (0.04mg) should never be exceeded in these patients.

Anesthetic effects of a combination of medetomidine, midazolam and butorphanol on the production of offspring in Japanese field vole, Microtus montebelli.

PubMed

Kageyama, Atsuko; Tohei, Atsushi; Ushijima, Hitoshi; Okada, Konosuke

2016-09-01

Pentobarbital sodium (Somnopentyl) can induce surgical anesthesia with a strong hypnotic effect that causes loss of consciousness. Animals have been known to die during experimental surgery under anesthesia with Somnopentyl, causing it to be declared inadequate as a general anesthetic for single treatment. An anesthetic combination of 0.3 mg/kg medetomidine, 4.0 mg/kg midazolam and 5.0 mg/kg butorphanol (M/M/B:0.3/4/5) was reported to induce anesthesia for a duration of around 40 min in ICR mice; similar anesthetic effects were reported in both male and female BALB/c and C57BL/6J strains of mice. However, the anesthetic effects of this combination in Japanese field vole, Microtus montebelli, remain to be evaluated. In the present study, we assessed the effects of Somnopentyl and different concentrations of anesthetic combination (M/M/B:0.3/4/5, 0.23/3/3.75 or 0.15/2/2.5) in Japanese field voles, by means of anesthetic scores. We also examined effect of these anesthetics on production of offspring. Death of the animals was observed only with Somnopentyl. The anesthetic score of Somnopentyl was lower than those of the other anesthetics, although there were no significant differences in duration, body weight and frequency of respiratory among the evaluated anesthetics. Abortion rate with Somnopentyl was significantly higher than that with the M/M/B:0.23/3/3.75 combination, although there was no significant difference in the number of offspring between two. In conclusion, results of this study provide basic information for achieving appropriate anesthetic concentrations in addition to indicating a new, safe and effective surgical anesthetic for Japanese field voles.

Binding of volatile anesthetics to serum albumin: measurements of enthalpy and solvent contributions.

PubMed

Sawas, Abdul H; Pentyala, Srinivas N; Rebecchi, Mario J

2004-10-05

This study directly examines the enthalpic contributions to binding in aqueous solution of closely related anesthetic haloethers (desflurane, isoflurane, enflurane, and sevoflurane), a haloalkane (halothane), and an intravenous anesthetic (propofol) to bovine and human serum albumin (BSA and HSA) using isothermal titration calorimetry. Binding to serum albumin is exothermic, yielding enthalpies (DeltaH(obs)) of -3 to -6 kcal/mol for BSA with a rank order of apparent equilibrium association constants (K(a) values): desflurane > isoflurane approximately enflurane > halothane >or= sevoflurane, with the differences being largely ascribed to entropic contributions. Competition experiments indicate that volatile anesthetics, at low concentrations, share the same sites in albumin previously identified in crystallographic and photo-cross-linking studies. The magnitude of the observed DeltaH increased linearly with increased reaction temperature, reflecting negative changes in heat capacities (DeltaC(p)). These -DeltaC(p) values significantly exceed those calculated for burial of each anesthetic in a hydrophobic pocket. The enhanced stabilities of the albumin/anesthetic complexes and -DeltaC(p) are consistent with favorable solvent rearrangements that promote binding. This idea is supported by substitution of D(2)O for H(2)O that significantly reduces the favorable binding enthalpy observed for desflurane and isoflurane, with an opposing increase of DeltaS(obs). From these results, we infer that solvent restructuring, resulting from release of water weakly bound to anesthetic and anesthetic-binding sites, is a dominant and favorable contributor to the enthalpy and entropy of binding to proteins.

Advances in local anesthesia in dentistry.

PubMed

Ogle, Orrett E; Mahjoubi, Ghazal

2011-07-01

Local pain management is the most critical aspect of patient care in dentistry. The improvements in agents and techniques for local anesthesia are probably the most significant advances that have occurred in dental science. This article provides an update on the most recently introduced local anesthetic agents along with new technologies used to deliver local anesthetics. Safety devices are also discussed, along with an innovative method for reducing the annoying numbness of the lip and tongue following local anesthesia. Copyright © 2011 Elsevier Inc. All rights reserved.

Comparison of Different Muscle-Relaxant Anesthetics on Growth, Migration and Invasion of Gastric Cancer Cells.

PubMed

Jiang, Aihua; Zhao, Huishan; Liu, Xiaofei; Yu, Mingwei; Chen, Jian; Jiang, Wen G

2017-08-01

Muscle relaxants, also known as neuromuscular blocking agents, can block nerve impulses to the muscles and are always used in surgery for general anesthesia. However, the effect of muscle-relaxant anesthetics on cell activity in gastric cancer is currently unknown. The present study aimed to examine and compare the role of three different muscle-relaxant anesthetics in gastric cancer cells. Gastric cancer cells (SGC7901 and BGC 823) were treated with a different dose of muscle-relaxant anesthetics, Rocuronium bromide (Rb), Vecuronium bromide (Vb) and Cisatracurium Besilate (CB). Using in vitro models, the effects on gastric cancer cell invasion, growth and migration of various anesthetics were subsequently investigated. We found that Rb increased the growth, invasion and migration of gastric cancer cells SGC7901 and BGC823. However, Vb and CB, as relatively mitigative anesthetics, did not significantly affect gastric cancer cell malignant phenotype at their regular blood concentration. Our results are important in selecting the type and dose of anesthetic used for surgery of gastric cancer patients. An understanding of the effect of muscle-relaxant anesthetics and their impact on tumor metastasis is critical, since it provides insight into the appropriate anesthetic strategy that could improve long-term survival in some patients with gastric cancer. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

The environmental impact of the Glostavent® anesthetic machine.

PubMed

Eltringham, Roger J; Neighbour, Robert C

2015-06-01

Because anesthetic machines have become more complex and more expensive, they have become less suitable for use in the many isolated hospitals in the poorest countries in the world. In these situations, they are frequently unable to function at all because of interruptions in the supply of oxygen or electricity and the absence of skilled technicians for maintenance and servicing. Despite these disadvantages, these machines are still delivered in large numbers, thereby expending precious resources without any benefit to patients. The Glostavent was introduced primarily to enable an anesthetic service to be delivered in these difficult circumstances. It is smaller and less complex than standard anesthetic machines and much less expensive to produce. It combines a drawover anesthetic system with an oxygen concentrator and a gas-driven ventilator. It greatly reduces the need for the purchase and transport of cylinders of compressed gases, reduces the impact on the environment, and enables considerable savings. Cylinder oxygen is expensive to produce and difficult to transport over long distances on poor roads. Consequently, the supply may run out. However, when using the Glostavent, oxygen is normally produced at a fraction of the cost of cylinders by the oxygen concentrator, which is an integral part of the Glostavent. This enables great savings in the purchase and transport cost of oxygen cylinders. If the electricity fails and the oxygen concentrator ceases to function, oxygen from a reserve cylinder automatically provides the pressure to drive the ventilator and oxygen for the breathing circuit. Consequently, economy is achieved because the ventilator has been designed to minimize the amount of driving gas required to one-seventh of the patient's tidal volume. Additional economies are achieved by completely eliminating spillage of oxygen from the breathing system and by recycling the driving gas into the breathing system to increase the Fraction of Inspired Oxygen

Screening of formulation variables for the preparation of poly(epsilon-caprolactone) nanocapsules containing the local anesthetic benzocaine.

PubMed

Moraes, Carolina Morales; de Matos, Angélica Prado; Grillo, Renato; de Melo, Nathalie F S; de Paula, Eneida; Dias Filho, Newton Luiz; Rosa, André Henrique; Fraceto, Leonardo Fernandes

2011-03-01

In this work we describe the screening of four parameters in the preparation, by nanoprecipitation, of poly(epsilon-caprolactone) nanocapsules, used as a drug carrier system for the local anesthetic, benzocaine. A 2(4-1) factorial experimental design was used to study the influence of four different independent variables (polymer, oily phase, Span 60 and Tween 80) on nanocapsule characteristics (size, polydispersion index, zeta potential) and drug loading capability. Best results were obtained using an aqueous formulation comprising 100 mg of polymer, 200 mg of oily phase, 40 mg of Span 60 and 60 mg of Tween 80 in a final volume of 10 mL which produced a colloidal system with particle size of 188 nm, zeta potential -32 mV, polydispersion index 0.07, and benzocaine association efficiency > 87%. These findings open the way for future clinical studies using such formulations.

Genotoxicity of Anesthetics Evaluated In Vivo (Animals)

PubMed Central

Karahalil, Bensu

2015-01-01

The anesthesia has been improved all over the years. However, it can have impact on health, in both patients and animals anesthetized, as well as professionals exposed to inhaled anesthetics. There is continuing effort to understand the possible effects of anesthetics at molecular levels. Knowing the effects of anesthetic agents on genetic material could be a valuable basic support to better understand the possible mechanisms of these agents. Thus, the purpose of this review is to provide an overview on the genotoxic potential, evaluated in animal models, of many anesthetics that have already been used and those currently used in anesthesia. PMID:26199936

A Conserved Behavioral State Barrier Impedes Transitions between Anesthetic-Induced Unconsciousness and Wakefulness: Evidence for Neural Inertia

PubMed Central

Friedman, Eliot B.; Sun, Yi; Moore, Jason T.; Hung, Hsiao-Tung; Meng, Qing Cheng; Perera, Priyan; Joiner, William J.; Thomas, Steven A.; Eckenhoff, Roderic G.; Sehgal, Amita; Kelz, Max B.

2010-01-01

One major unanswered question in neuroscience is how the brain transitions between conscious and unconscious states. General anesthetics offer a controllable means to study these transitions. Induction of anesthesia is commonly attributed to drug-induced global modulation of neuronal function, while emergence from anesthesia has been thought to occur passively, paralleling elimination of the anesthetic from its sites in the central nervous system (CNS). If this were true, then CNS anesthetic concentrations on induction and emergence would be indistinguishable. By generating anesthetic dose-response data in both insects and mammals, we demonstrate that the forward and reverse paths through which anesthetic-induced unconsciousness arises and dissipates are not identical. Instead they exhibit hysteresis that is not fully explained by pharmacokinetics as previously thought. Single gene mutations that affect sleep-wake states are shown to collapse or widen anesthetic hysteresis without obvious confounding effects on volatile anesthetic uptake, distribution, or metabolism. We propose a fundamental and biologically conserved concept of neural inertia, a tendency of the CNS to resist behavioral state transitions between conscious and unconscious states. We demonstrate that such a barrier separates wakeful and anesthetized states for multiple anesthetics in both flies and mice, and argue that it contributes to the hysteresis observed when the brain transitions between conscious and unconscious states. PMID:20689589

Ethyl-p-aminobenzoate (Benzocaine): efficacy as an anesthetic for five species of freshwater fish

USGS Publications Warehouse

Dawson, V.K.; Gilderhus, P.A.

1979-01-01

Ethyl-p-aminobenzoate (benzocaine) was tested for its efficacy as an anesthetic for rainbow trout (Salmo gairdnerii, brown trout (Salmo truttas, northern pike (Esox lucius). carp (Cyprinus carpio), and largemouth bass (Mieropterus salmoidesi. Since benzocaine is not water soluble, it was applied with acetone as a carrier. Concentrations of 100 to 200 mg!l were required for large adult northern pike, compared with 50 to 100 mg/l for small fish. Rates of sedation and recovery were slower in cold water than in warm water. Water hardness had little influence on the activity of benzocaine. Fish were anesthetized faster and recovered more slowly in acid than in alkaline water. Benzocaine produced deep anesthesia, but concentrations that rendered the fish handleable within 5 min were generally not safe for exposures longer than 15 min. Concentrations of benzocaine efficacious for fish were not acutely toxic to eggs of coho salmon (Oncorhynchus kisutch), chinook salmon (Oncorhynchus tshauiytschas, rainbow trout, brown trout, or lake trout (Salvelinus namaycush). Benzocaine is not registered for fishery use and is neither more effective nor safer than the registered anesthetic, tricaine methanesulfonate (MS-222l.

Anesthetic biotransformation and renal function in obese patients during and after methoxyflurane or halothane anesthesia.

PubMed

Young, S R; Stoelting, R K; Peterson, C; Madura, J A

1975-04-01

Anesthetic biotransformation and renal function were studied in obese adult patients (148 plus or minus 8 kg; mean plus or minus SE) anesthetized for three hours with 60 per cent nitrous oxide plus either methoxyflurane or halothane for elective jejunoileal small-bowel-bypass operations. There was no evidence of persistent renal dysfunction in any patient postoperatively, but serum osmolality was elevated 72 hours after methoxyflurane anesthesia. Urine concentrating ability was not determined. Peak serum ionic fluoride concentration was 55.8 plus or minus 5.8 muM/1 two hours after discontinuation of methoxyflurane. Urinary ionic fluoride and oxalate excretions increased postoperatively. Compared with previously reported data from nonobese patients, serum ionic fluoride concentrations in obese patients increased more rapidly during methoxyflurane anesthesia and peaked higher and sooner after discontinuation of methoxyflurane. The peak serum ionic fluoride concentration was 10.4 plus or minus 1.5 muM/1 at the conclusion of halothane anesthesia, significantly more than the corresponding value in nonobese patients. Intraoperative liver biopsies from 23 of 27 patients showed moderate to severe fatty metamorphosis. Fatty liver infiltration may have increased hepatic anesthetic uptake and exposed more methoxyflurane or halothane to hepatic microsomal enzymes. The more rapid elevation and higher peak levels of serum ionic fluoride following methoxyflurane, and to a lesser extent following halothane, may reflect increased anesthetic biotransformation in obese compared with nonobese patients. To avoid excessive serum ionic fluoride elevations the authors recommended limiting low-dose methoxyflurane anesthesia delivered to obese patients with potential fatty liver infiltration to no more than three hours.

Hemodynamic changes associated with a novel concentration of lidocaine HCl for impacted lower third molar surgery.

PubMed

Ping, Bushara; Kiattavorncharoen, Sirichai; Durward, Callum; Im, Puthavy; Saengsirinavin, Chavengkiat; Wongsirichat, Natthamet

2015-09-01

The authors studied the hemodynamic effect influent by using the novel high concentration of lidocaine HCl for surgical removal impacted lower third molar. The objective of this study was to evaluate the hemodynamic change when using different concentrations of lidocaine in impacted lower third molar surgery. Split mouth single blind study comprising 31 healthy patients with a mean age of 23 years (range 19-33 years). Subjects had symmetrically impacted lower third molars as observed on panoramic radiograph. Each participant required 2 surgical interventions by the same surgeon with a 3-week washout period washout period. The participants were alternately assigned one of two types of local anesthetic (left or right) for the first surgery, then the other type of anesthetic for the second surgery. One solution was 4% lidocaine with 1:100,000 epinephrine and the other was 2% lidocaine with 1:100,000 epinephrine. A standard IANB with 1.8 ml volume was used. Any requirement for additional anesthetic and patient pain intra-operation was recorded. Post-operatively, patient was instructed to fill in the patient report form for any adverse effect and local anesthetic preference in terms of intra-operative pain. This form was collected at the seven day follow up appointment. In the 4% lidocaine group, the heart rate increased during the first minute post-injection (P < 0.05). However, there was no significant change in arterial blood pressure during the operation. In the 2% lidocaine group, there was a significant increase in arterial blood pressure and heart rate in the first minute following injection for every procedure. When the hemodynamic changes in each group were compared, the 4% lidocaine group had significantly lower arterial blood pressure compared to the 2% lidocaine group following injection. Post-operatively, no adverse effects were observed by the operator and patient in either local anesthetic group. Patients reported less pain intra-operation in the 4

Administration of anesthetic and analgesic prevent the suppression of many leukocyte responses following surgical castration and physical dehorning.

PubMed

Ballou, M A; Sutherland, M A; Brooks, T A; Hulbert, L E; Davis, B L; Cobb, C J

2013-02-15

intensity of peripheral blood neutrophils when co-cultured with an Escherichia coli. The effects of castration and dehorning on blood leukocyte counts or any of the leukocyte responses were not additive (P>0.23). Castration and dehorning effects of plasma haptoglobin concentrations tended (P=0.10) to be additive at 72 h after the procedure(s). Prior administration of local anesthetic and a systemic analgesic attenuated (P<0.001) the cortisol response and prevented (P=0.03) the observed leukocytosis, neutrophilia, and leukocyte suppression. These data suggest that calves should be castrated and dehorned on the same day rather than spreading them out across two days and calves should be administered pain relief prior to performing either procedure. Copyright © 2012 Elsevier B.V. All rights reserved.

Binding Site and Affinity Prediction of General Anesthetics to Protein Targets Using Docking

PubMed Central

Liu, Renyu; Perez-Aguilar, Jose Manuel; Liang, David; Saven, Jeffery G.

2012-01-01

Background The protein targets for general anesthetics remain unclear. A tool to predict anesthetic binding for potential binding targets is needed. In this study, we explore whether a computational method, AutoDock, could serve as such a tool. Methods High-resolution crystal data of water soluble proteins (cytochrome C, apoferritin and human serum albumin), and a membrane protein (a pentameric ligand-gated ion channel from Gloeobacter violaceus, GLIC) were used. Isothermal titration calorimetry (ITC) experiments were performed to determine anesthetic affinity in solution conditions for apoferritin. Docking calculations were performed using DockingServer with the Lamarckian genetic algorithm and the Solis and Wets local search method (https://www.dockingserver.com/web). Twenty general anesthetics were docked into apoferritin. The predicted binding constants are compared with those obtained from ITC experiments for potential correlations. In the case of apoferritin, details of the binding site and their interactions were compared with recent co-crystallization data. Docking calculations for six general anesthetics currently used in clinical settings (isoflurane, sevoflurane, desflurane, halothane, propofol, and etomidate) with known EC50 were also performed in all tested proteins. The binding constants derived from docking experiments were compared with known EC50s and octanol/water partition coefficients for the six general anesthetics. Results All 20 general anesthetics docked unambiguously into the anesthetic binding site identified in the crystal structure of apoferritin. The binding constants for 20 anesthetics obtained from the docking calculations correlate significantly with those obtained from ITC experiments (p=0.04). In the case of GLIC, the identified anesthetic binding sites in the crystal structure are among the docking predicted binding sites, but not the top ranked site. Docking calculations suggest a most probable binding site located in the

Effects of deuteration on the metabolism of halogenated anesthetics in the rat

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCarty, L.P.; Malek, R.S.; Larsen, E.R.

1979-08-01

The authors studied the effects of substituting deuterium for hydrogen in several volatile anesthetics on their metabolism in the Fischer rat. Substitution of deuterium in the ethyl portion of methoxyflurane increased the metabolic production of fluoride ion by 19 percent when administered at a concentration of 0.05%. Total replacement of hydrogen by deuterium resulted in a 29% decrease in the amount of fluoride produced, while deuteration of only the methoxyl group produced a 33% decrease in fluoride produced. Deuteration of halothane resulted in a 15 or 26% decrease in serum bromide at 0.75% or 1.0%, respectively. Deuteration in the ethylmore » portions of enflurane and two experimental agents, CF2HOCF2CFBrH and CF2HOCF2CCl2H resulted in 65, 76, and 29% decreases in urinary fluoride, respectively. Anesthesia with deuterated chloroform at a concentration of 0.36% produced a 35% decrease in serum glutamic pyruvic transaminase (SGPT). It is concluded that deuteration of volatile anesthetics changes their metabolism, in most cases producing decreases in metabolism. This effect may lessen the organ toxicity believed to occur with some of these anesthetics.« less

Drug binding to the acetylcholine receptor: Nitroxide analogs of phencyclidine and a local anesthetic

DOE Office of Scientific and Technical Information (OSTI.GOV)

Palma, A.L.

1988-01-01

The interaction of noncompetitive inhibitors (NCIs) with Torpedo californica native nicotinic acetylcholine receptor (nAChR) membranes was examined primarily by the technique of electron paramagnetic resonance (EPR) spectroscopy. The goal of this work being to define some of the physical characteristics for the site(s) of association between an NCI and the nAChR membrane. A nitroxide labeled analog of a quaternary amine local anesthetic, 2-(N,N-dimethyl-N-4-(2,2,6,6-tetramethylpiperidinoxyl)amino)-ethyl 4-hexyloxybenzoate iodide (C6SLMeI), displays a strongly immobilized EPR component when added to nAChR membranes in the presence of carbamylcholine (carb). To further this work, a nitroxide labeled analog of phencyclidine (PCP), a potent NCI, was synthesized. 4-phenyl-4-(1-piperidinyl)-2,2,6,6-tetramethylpiperidinoxylmore » (PPT) exhibited one-third the potency of PCP in inhibiting nAChR mediated ion flux, and from competition binding studies with ({sup 3}H)PCP displayed a K{sub D} of 0.21 {mu}M towards a carb desensitized nAChR and a K{sub 0.5} of 18 {mu}M for a resting {alpha}-bungarotoxin treated nAChR.« less

Neurogenesis and Developmental Anesthetic Neurotoxicity

PubMed Central

Kang, Eunchai; Berg, Daniel A.; Furmanski, Orion; Jackson, William M.; Ryu, Yun Kyoung; Gray, Christy D.; Mintz, C. David

2017-01-01

The mechanism by which anesthetics might act on the developing brain in order to cause long term deficits remains incompletely understood. The hippocampus has been identified as a structure that is likely to be involved, as rodent models show numerous deficits in behavioral tasks of learning that are hippocampal-dependent. The hippocampus is an unusual structure in that it is the site of large amounts of neurogenesis postnatally, particularly in the first year of life in humans, and these newly generated neurons are critical to the function of this structure. Intriguingly, neurogenesis is a major developmental event that occurs during postulated windows of vulnerability to developmental anesthetic neurotoxicity across the different species in which it has been studied. In this review, we examine the evidence for anesthetic effects on neurogenesis in the early postnatal period and ask whether neurogenesis should be studied further as a putative mechanism of injury. Multiple anesthetics are considered, and both in vivo and in vitro work is presented. While there is abundant evidence that anesthetics act to suppress neurogenesis at several different phases, evidence of a causal link between these effects and any change in learning behavior remains elusive. PMID:27751818

Mechanisms involved in cardiac sensitization by volatile anesthetics: general applicability to halogenated hydrocarbons?

PubMed

Himmel, Herbert M

2008-01-01

An increased sensitivity of the heart to catecholamines or cardiac sensitization is a recognized risk during acute human exposure to halogenated hydrocarbons used as solvents, foam-blowing or fire-extinguishing agents, refrigerants, and aerosol propellants. Although cardiac sensitization to such "industrial" halocarbons can result in serious arrhythmia and death, research into its mechanistic basis has been limited, whereas the literature on volatile anesthetics (e.g., halothane, chloroform) is comparably extensive. A review of the literature on halocarbons and related volatile anesthetics was conducted. The available experimental evidence suggests that volatile anesthetics at physiologically relevant concentrations interact predominantly with the main repolarizing cardiac potassium channels hERG and I(Ks), as well as with calcium and sodium channels at slightly higher concentrations. On the level of the heart, inhibition of these ion channels is prone to alter both action potential shape (triangulation) and electrical impulse conduction, which may facilitate arrhythmogenesis by volatile anesthetics per se and is potentiated by catecholamines. Action potential triangulation by regionally heterogeneous inhibition of calcium and potassium channels will facilitate catecholamine-induced afterdepolarizations, triggered activity, and enhanced automaticity. Inhibition of cardiac sodium channels will reduce conduction velocity and alter refractory period; this is potentiated by catecholamines and promotes reentry arrhythmias. Other cardiac and/or neuronal mechanisms might also contribute to arrhythmogenesis. The few scattered in vitro data available for halocarbons (e.g., FC-12, halon 1301, trichloroethylene) suggest inhibition of cardiac sodium (conduction), calcium and potassium channels (triangulation), extraneuronal catecholamine reuptake, and various neuronal ion channels. Therefore, it is hypothesized that halocarbons promote cardiac sensitization by similar

Trace anesthetic vapors in hospital operating-room environments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choi-Lao, A.T.

1981-05-01

This study investigated concentrations of halothane anesthetic vapors in the operating rooms of two hospitals in the Ottawa, Ontario, Canada, area. Air samples, taken by active charcoal tubes and dosimeter badges, were analyzed by a gas chromatographic technique. Readings of 71 samples taken from hospital A and 65 samples from hospital B ranged from 1.0 to 29.4 parts per billion (ppb) for the active period and 0.1 to 3.8 ppb for the inactive period. All samples showed trace concentrations of halothane, but were well below the recommended maximal level.

The anesthetic action of some polyhalogenated ethers-Monte Carlo method based QSAR study.

PubMed

Golubović, Mlađan; Lazarević, Milan; Zlatanović, Dragan; Krtinić, Dane; Stoičkov, Viktor; Mladenović, Bojan; Milić, Dragan J; Sokolović, Dušan; Veselinović, Aleksandar M

2018-04-13

Up to this date, there has been an ongoing debate about the mode of action of general anesthetics, which have postulated many biological sites as targets for their action. However, postoperative nausea and vomiting are common problems in which inhalational agents may have a role in their development. When a mode of action is unknown, QSAR modelling is essential in drug development. To investigate the aspects of their anesthetic, QSAR models based on the Monte Carlo method were developed for a set of polyhalogenated ethers. Until now, their anesthetic action has not been completely defined, although some hypotheses have been suggested. Therefore, a QSAR model should be developed on molecular fragments that contribute to anesthetic action. QSAR models were built on the basis of optimal molecular descriptors based on the SMILES notation and local graph invariants, whereas the Monte Carlo optimization method with three random splits into the training and test set was applied for model development. Different methods, including novel Index of ideality correlation, were applied for the determination of the robustness of the model and its predictive potential. The Monte Carlo optimization process was capable of being an efficient in silico tool for building up a robust model of good statistical quality. Molecular fragments which have both positive and negative influence on anesthetic action were determined. The presented study can be useful in the search for novel anesthetics. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effects of Anesthetics on Brain Circuit Formation

PubMed Central

Wagner, Meredith; Ryu, Yun Kyoung; Smith, Sarah C.; Mintz, C. David

2014-01-01

The results of several retrospective clinical studies suggest that exposure to anesthetic agents early in life is correlated with subsequent learning and behavioral disorders. While ongoing prospective clinical trials may help to clarify this association, they remain confounded by numerous factors. Thus, some of the most compelling data supporting the hypothesis that a relatively short anesthetic exposure can lead to a long-lasting change in brain function are derived from animal models. The mechanism by which such changes could occur remains incompletely understood. Early studies identified anesthetic-induced neuronal apoptosis as a possible mechanism of injury, and more recent work suggests that anesthetics may interfere with several critical processes in brain development. The function of the mature brain requires the presence of circuits, established during development, that perform the computations underlying learning and cognition. In this review we examine the mechanisms by which anesthetics could disrupt brain circuit formation, including effects on neuronal survival and neurogenesis, neurite growth and guidance, formation of synapses, and function of supporting cells. There is evidence that anesthetics can disrupt aspects of all of these processes, and further research is required to elucidate which are most relevant to pediatric anesthetic neurotoxicity. PMID:25144504

Photoacoustic microscopy of cerebral hemodynamic and oxygen-metabolic responses to anesthetics

NASA Astrophysics Data System (ADS)

Cao, Rui; Li, Jun; Ning, Bo; Sun, Naidi; Wang, Tianxiong; Zuo, Zhiyi; Hu, Song

2017-02-01

General anesthetics are known to have profound effects on cerebral hemodynamics and neuronal activities. However, it remains a challenge to directly assess anesthetics-induced hemodynamic and oxygen-metabolic changes from the true baseline under wakefulness at the microscopic level, due to the lack of an enabling technology for high-resolution functional imaging of the awake mouse brain. To address this challenge, we have developed head-restrained photoacoustic microscopy (PAM), which enables simultaneous imaging of the cerebrovascular anatomy, total concentration and oxygen saturation of hemoglobin (CHb and sO2), and blood flow in awake mice. From these hemodynamic measurements, two important metabolic parameters, oxygen extraction fraction (OEF) and the cerebral metabolic rate of oxygen (CMRO2), can be derived. Side-by-side comparison of the mouse brain under wakefulness and anesthesia revealed multifaceted cerebral responses to isoflurane, a volatile anesthetic widely used in preclinical research and clinical practice. Key observations include elevated cerebral blood flow (CBF) and reduced oxygen extraction and metabolism.

Neurogenesis and developmental anesthetic neurotoxicity.

PubMed

Kang, Eunchai; Berg, Daniel A; Furmanski, Orion; Jackson, William M; Ryu, Yun Kyoung; Gray, Christy D; Mintz, C David

The mechanism by which anesthetics might act on the developing brain in order to cause long term deficits remains incompletely understood. The hippocampus has been identified as a structure that is likely to be involved, as rodent models show numerous deficits in behavioral tasks of learning that are hippocampal-dependent. The hippocampus is an unusual structure in that it is the site of large amounts of neurogenesis postnatally, particularly in the first year of life in humans, and these newly generated neurons are critical to the function of this structure. Intriguingly, neurogenesis is a major developmental event that occurs during postulated windows of vulnerability to developmental anesthetic neurotoxicity across the different species in which it has been studied. In this review, we examine the evidence for anesthetic effects on neurogenesis in the early postnatal period and ask whether neurogenesis should be studied further as a putative mechanism of injury. Multiple anesthetics are considered, and both in vivo and in vitro work is presented. While there is abundant evidence that anesthetics act to suppress neurogenesis at several different phases, evidence of a causal link between these effects and any change in learning behavior remains elusive. Copyright © 2016. Published by Elsevier Inc.

Survey of responsible handling of local anesthetic in Indian dental operatory

PubMed Central

Rooban, Thavarajah; Rao, Umadevi Krishnamohan; Joshua, Elizabeth; Ranganathan, Kannan

2013-01-01

Background: Dental operatory requires handling of numerous toxic fluids such as denture acrylic monomer, alcohol and formalin for effective oral care delivery. The efficacy and responsible handling of such fluids has not been analyzed among Indian dentists and this study aims to address this lacunae. Materials and Methods: Closed ended questionnaire was distributed through email to Indian dentists in July 2012. After inclusion/exclusion criteria, 1484 practitioners constituted the study group with a response rate of 52%. Statistics: SPSS® Version 17.0 (SPSS-IBM Inc., IL, USA) was used to carry out statistical analysis. Descriptive statistics were presented. Chi square test was used to identify the association between the parameters; P ≤ 0.05 was considered as statistically significant. Results: Males (80.8%), undergraduates (78%), exclusive practitioners (81.2%), urban practitioners (68.5%) were the predominant respondents. Predominant of the respondents (97%) used local anesthetic (LA) from bottles. Eight percent have encountered instances of injecting formalin instead of LA in their settings. Safe disposal rules and regulations (P ≤ 0.05), opinion on injecting the other fluids instead of LA as a severe negligent act (P ≤ 0.05) were statistically significant between age groups. Educational status did not appear to influence the outcome. Only a third of the respondents were aware of the rules and regulations for safe disposal of empty LA bottles while 49.1% were not aware of them and willing to learn. Discussion: The lacunae in responsible handling of toxic fluids need to be addressed to prevent inadvertent and negligence suits against dentists, highlighting the need through continuing dental education programmes. PMID:24255564

Evaluation of Five Anesthetics on Striped Bass.

DTIC Science & Technology

1993-01-01

mg/L MS-222, 25 mg/L benzocaine , 5 mg/L quinaldine, 5 mg/L quinaldine sulfate, and 0.5 mg/L metomidate. The lowest effective concentrations for...each anesthetic were 150, 150, and 150 mg(L for MS-222; 85-100, 70, and 55 mg/L for benzocaine ; 40, 25, and 25 mg/L for quinaldine; 55, 25, and 25 mg/L for quinaldine sulfate; and 7.5, 10, and 10 mg/L for metomidate.

Anesthetic drugs and onset of malignant hyperthermia.

PubMed

Visoiu, Mihaela; Young, Michael C; Wieland, Keith; Brandom, Barbara W

2014-02-01

The time between the beginning of anesthetic administration and recognition of the first sign of malignant hyperthermia (MH) (MH onset time) could differ among anesthetic drugs. We examined the time of the first signs of suspected MH, anesthetic drugs administered, subject age, and year of event in Adverse Metabolic/Musculoskeletal Reaction to Anesthesia reports in the North American Malignant Hyperthermia Registry. Inclusion criteria were judgment by the reporting clinician that the event was possible or fulminant MH, documentation of the time when anesthetic administration began, and the time when the first MH sign was noted. Descriptive statistics, Kruskal-Wallis analysis, and nonparametric correlation were used to assess the difference in MH onset times under different conditions. Four hundred seventy-seven cases met inclusion criteria; 58.5% were possible MH and 41.5% fulminant MH. Inhaled anesthetic and succinylcholine were given in 53.9% of cases, inhaled anesthetic only in 41.7%, and succinylcholine without inhaled anesthetics in 2.9%. No causative anesthetic drugs were reported in 7 MH cases. In 394 patients exposed to only 1 of the 4 inhaled anesthetics, without regard for subject age, MH onset time was shorter in the presence of halothane than any of the other anesthetics and shorter after succinylcholine in all anesthetics. If succinylcholine was not given, MH onset was shorter during sevoflurane anesthesia than during desflurane or isoflurane. In 322 cases, 1 rather than multiple first signs of MH were reported with masseter spasm as the earliest MH sign. In 339 cases in which masseter spasm was not reported, there was no difference in MH onset time with or without succinylcholine. In 146 cases in which masseter spasm was not reported and succinylcholine was not given, MH onset was shorter during halothane anesthesia, than during exposure to desflurane, or isoflurane. MH onset time during sevoflurane was shorter than during desflurane or isoflurane. MH

21 CFR 868.5550 - Anesthetic gas mask.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Anesthetic gas mask. 868.5550 Section 868.5550...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5550 Anesthetic gas mask. (a) Identification. An anesthetic gas mask is a device, usually made of conductive rubber, that is positioned over a...

21 CFR 868.5550 - Anesthetic gas mask.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Anesthetic gas mask. 868.5550 Section 868.5550...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5550 Anesthetic gas mask. (a) Identification. An anesthetic gas mask is a device, usually made of conductive rubber, that is positioned over a...

46 CFR 111.105-37 - Flammable anesthetics.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 4 2010-10-01 2010-10-01 false Flammable anesthetics. 111.105-37 Section 111.105-37...-GENERAL REQUIREMENTS Hazardous Locations § 111.105-37 Flammable anesthetics. Each electric installation where a flammable anesthetic is used or stored must meet NFPA 99 (incorporated by reference, see 46 CFR...

46 CFR 111.105-37 - Flammable anesthetics.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 4 2011-10-01 2011-10-01 false Flammable anesthetics. 111.105-37 Section 111.105-37...-GENERAL REQUIREMENTS Hazardous Locations § 111.105-37 Flammable anesthetics. Each electric installation where a flammable anesthetic is used or stored must meet NFPA 99 (incorporated by reference, see 46 CFR...

21 CFR 868.5550 - Anesthetic gas mask.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Anesthetic gas mask. 868.5550 Section 868.5550...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5550 Anesthetic gas mask. (a) Identification. An anesthetic gas mask is a device, usually made of conductive rubber, that is positioned over a...

46 CFR 111.105-37 - Flammable anesthetics.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 4 2012-10-01 2012-10-01 false Flammable anesthetics. 111.105-37 Section 111.105-37...-GENERAL REQUIREMENTS Hazardous Locations § 111.105-37 Flammable anesthetics. Each electric installation where a flammable anesthetic is used or stored must meet NFPA 99 (incorporated by reference, see 46 CFR...

21 CFR 868.5550 - Anesthetic gas mask.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Anesthetic gas mask. 868.5550 Section 868.5550...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5550 Anesthetic gas mask. (a) Identification. An anesthetic gas mask is a device, usually made of conductive rubber, that is positioned over a...

21 CFR 868.5550 - Anesthetic gas mask.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Anesthetic gas mask. 868.5550 Section 868.5550...) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5550 Anesthetic gas mask. (a) Identification. An anesthetic gas mask is a device, usually made of conductive rubber, that is positioned over a...

46 CFR 111.105-37 - Flammable anesthetics.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 4 2013-10-01 2013-10-01 false Flammable anesthetics. 111.105-37 Section 111.105-37...-GENERAL REQUIREMENTS Hazardous Locations § 111.105-37 Flammable anesthetics. Each electric installation where a flammable anesthetic is used or stored must meet NFPA 99 (incorporated by reference, see 46 CFR...

46 CFR 111.105-37 - Flammable anesthetics.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 4 2014-10-01 2014-10-01 false Flammable anesthetics. 111.105-37 Section 111.105-37...-GENERAL REQUIREMENTS Hazardous Locations § 111.105-37 Flammable anesthetics. Each electric installation where a flammable anesthetic is used or stored must meet NFPA 99 (incorporated by reference, see 46 CFR...

Anesthetic management for Cesarean delivery in parturients with a diagnosis of dwarfism.

PubMed

Lange, Elizabeth M S; Toledo, Paloma; Stariha, Jillian; Nixon, Heather C

2016-08-01

The literature on the anesthetic management of parturients with dwarfism is sparse and limited to isolated case reports. Pregnancy complications associated with dwarfism include an increased risk of respiratory compromise, an increased risk of Cesarean delivery, and an unpredictable degree of anesthesia with neuraxial techniques. Therefore, we conducted this retrospective review to evaluate the anesthetic management of parturients with a diagnosis of dwarfism. We used a query of billing data to identify short statured women who underwent a Cesarean delivery during May 1, 2008 to May 1, 2013. We then hand searched the electronic medical record for qualifying patients with heights < 148 cm and a diagnosis of dwarfism. The extracted data included patient demographics and obstetric and anesthetic information. We identified 13 women with dwarfism who had 15 Cesarean deliveries in total. Twelve of the women had disproportionate dwarfism, and ten of the 15 Cesarean deliveries were due to cephalopelvic disproportion. Neuraxial anesthesia was attempted in 93% of deliveries. The dose chosen for initiation of neuraxial anesthesia was lower than the typical doses used in parturients of normal stature. Neuraxial anesthetic complications included difficult neuraxial placement (64%), high spinal (7%), inadequate surgical level (13%), and unrecognized intrathecal catheter (7%). The data collected suggest that females with a diagnosis of dwarfism may have difficult neuraxial placement and potentially require lower dosages of local anesthetic for both spinal and epidural anesthesia to achieve adequate surgical blockade.

Effects of ampicillin/sulbactam and enrofloxacin on the blood pressure of isoflurane anesthetized dogs.

PubMed

Moorer, Jeremiah D; Towle-Millard, Heather A; Gross, Marjorie E; Payton, Mark E

2013-01-01

A blinded, prospective, randomized crossover study was performed to determine the effects of ampicillin Na/sulbactam Na and enrofloxacin on the blood pressure (BP) of healthy anesthetized dogs. Eight dogs were anesthetized three different times. They randomly received enrofloxacin, ampicillin Na/sulbactam Na, and saline. Systolic, diastolic, and mean arterial BPs (SAP, DAP, and MAP, respectively), heart rate (HR), O2 saturation of hemoglobin, end-tidal CO2 (ETCO2) concentration, inspired isoflurane concentration, end-tidal isoflurane (ETiso) concentration, respiratory rate, electrocardiogram, and body temperature were measured for 20 min prior to administration of treatment, during administration over 30 min, and for 30 min after administration. There was no significant difference in the SAP or ETiso. There was no significant change in the arterial pressure values over time in the enrofloxacin and ampicillin Na/sulbactam Na groups. The control group's MAP increased over time and was increased compared with the enrofloxacin group at times 25, 35, 45, and 55. The statistical difference between the enrofloxacin and the control groups was due to an increase in the MAP in the control group, not a decrease in the enrofloxacin group's BP. Neither enrofloxacin nor ampicillin Na/sulbactam Na caused hypotension in healthy dogs anesthetized with isoflurane and fentanyl.

Anesthetic Sevoflurane Causes Rho-Dependent Filopodial Shortening in Mouse Neurons.

PubMed

Zimering, Jeffrey H; Dong, Yuanlin; Fang, Fang; Huang, Lining; Zhang, Yiying; Xie, Zhongcong

2016-01-01

Early postnatal anesthesia causes long-lasting learning and memory impairment in rodents, however, evidence for a specific neurotoxic effect on early synaptogenesis has not been demonstrated. Drebrin A is an actin binding protein whose localization in dendritic protrusions serves an important role in dendritic spine morphogenesis, and is a marker for early synaptogenesis. We therefore set out to investigate whether clinically-relevant concentrations of anesthetic sevoflurane, widely- used in infants and children, alters dendritic morphology in cultured fetal day 16 mouse hippocampal neurons. After 7 days in vitro, mouse hippocampal neurons were exposed to four hours of 3% sevoflurane in 95% air/5% CO2 or control condition (95% air/5% CO2). Neurons were fixed in 4% paraformaldehyde and stained with Alexa Fluor555-Phalloidin, and/or rabbit anti-mouse drebrin A/E antibodies which permitted subcellular localization of filamentous (F)-actin and/or drebrin immunoreactivity, respectively. Sevoflurane caused acute significant length-shortening in filopodia and thin dendritic spines in days-in-vitro 7 neurons, an effect which was completely rescued by co-incubating neurons with ten micromolar concentrations of the selective Rho kinase inhibitor Y27632. Filopodia and thin spine recovered in length two days after sevoflurane exposure. Yet cluster-type filopodia (a precursor to synaptic filopodia) were persistently significantly decreased in number on day-in-vitro 9, in part owing to preferential localization of drebrin immunoreactivity to dendritic shafts versus filopodial stalks. These data suggest that sevoflurane induces F-actin depolymerization leading to acute, reversible length-shortening in dendritic protrusions through a mechanism involving (in part) activation of RhoA/Rho kinase signaling and impairs localization of drebrin A to filopodia required for early excitatory synapse formation.

Anesthetic activity and bio-guided fractionation of the essential oil of Aloysia gratissima (Gillies & Hook.) Tronc. in silver catfish Rhamdia quelen.

PubMed

Benovit, Simone C; Silva, Lenise L; Salbego, Joseânia; Loro, Vania L; Mallmann, Carlos A; Baldisserotto, Bernardo; Flores, Erico M M; Heinzmann, Berta M

2015-09-01

This work aimed to determine the efficacy of the essential oil of A. gratissima as anesthetic for silver catfish, and to perform the bio-guided fractionation of essential oil aiming to isolate compounds responsible for the noted effects. Fish were submitted to anesthesia bath with essential oil, its fractions and isolated compounds to determine time of anesthetic induction and recovery. Eugenol (50 mg L(-1)) was used as positive control. Essential oil of A. gratissima was effective as an anesthetic at concentrations of 300 to 900 mg L(-1). Fish presented involuntary muscle contractions during induction and recovery. The bio-guided fractionation of essential oil furnished E-(-)-pinocamphone, (-)-caryophyllene oxide, (-)-guaiol and (+)-spathulenol. E-(-)-pinocamphone caused the same side effects observed for essential oil. (-)-Caryophyllene oxide, (-)-guaiol and (+)-spathulenol showed only sedative effects at proportional concentrations to those of the constituents in essential oil. (+)-Spathulenol (51.2 mg L(-1)) promoted deep anesthesia without side effects. A higher concentration of (+)-spathulenol, and lower or absent amounts ofE-(-)-pinocamphone could contribute to increase the activity and safety of the essential oil of A. gratissima. (+)-Spathulenol showed potent sedative and anesthetic activities in silver catfish, and could be considered as a viable compound for the development of a new anesthetic.

Distribution and absorption of local anesthetics in inferior alveolar nerve block: evaluation by magnetic resonance imaging.

PubMed

Ay, Sinan; Küçük, Dervisşhan; Gümüş, Cesur; Kara, M Isa

2011-11-01

The aim of this study was to evaluate the distribution and absorption of local anesthetic solutions in inferior alveolar nerve block using magnetic resonance imaging. Forty healthy volunteers were divided into 4 groups and injected with 1.5 mL for inferior alveolar nerve block and 0.3 mL for lingual nerve block. The solutions used for the different groups were 2% lidocaine, 2% lidocaine with 0.125 mg/mL epinephrine, 4% articaine with 0.006 mg/mL epinephrine, and 4% articaine with 0.012 mg/mL epinephrine. All subjects had axial T2-weighted and fat-suppressed images at 0, 60, and 120 minutes after injection. The localization, area, and intensity (signal characteristics) of the solutions were analyzed and onset and duration times of the anesthesia were recorded. There were no significant differences between groups with regard to the intensity and area of the solutions at 0, 60, and 120 minutes after injection, but differences were found within each group. No between-group differences were found on magnetic resonance imaging in the distribution and absorption of lidocaine with or without epinephrine and articaine with 0.006 and 0.012 mg/mL epinephrine. All solutions were noticeably absorbed at 120 minutes after injection. Copyright © 2011 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Nuclear magnetic resonance studies of the interaction of general anesthetics with 1,2-dihexadecyl-sn-glycero-3-phosphorylcholine bilayer.

PubMed Central

Shieh, D D; Ueda, I; Lin, H; Eyring, H

1976-01-01

Sonicated 1,2-dihexadecyl-sn-glycero-3-phosphorylcholine forms liposomes. Studies by Fourier transform proton magnetic resonance of the interaction of these bilayers with some general anesthetics, i.e., chloroform, halothane, methoxyflurane, and enflurane, show that the addition of a general anesthetic to the liposomes and raising the temperature have a similar effect in cuasing the fluidization of the bilayer. General anesthetics act on the hydrophilic site (choline group) in clinical concentrations and then diffuse into the hydrophobic region with the addition of larger amount of anesthetics. There is evidence that the lecithin choline groups are involved in the interaction with protein and that the general anesthetics change the conformation of some polypeptides and proteins. We conclude that the general anesthetics, by increasing the motion of positively charged choline groups and negatively charged groups in protein, weaken the Coulomb-type interaction and cause the liprotein conformational changes. PMID:1069285

Benzocaine as a fish anesthetic: efficacy and safety for spawning-phase salmon

USGS Publications Warehouse

Gilderhus, P.A.

1990-01-01

The anesthetic benzocaine was tested for efficacy and safety for spawning-phase chinook salmon (Oncorhynchus tshawytscha) and Atlantic salmon (Salmo salar) at federal fish hatcheries. Tests were conducted in the existing hatchery water supplies (soft water; temperatures, 10–13 °C. Crystalline benzocaine was dissolved in ethanol (1 g/30 mL), and aliquots of that stock solution were added to the water in test tanks. Benzocaine concentrations of 25–30 mg/L anesthetized most fish in less than 3.5 min, and most fish recovered in less than 10 min after 15 min of exposure. Safety margins were narrow; both species tolerated 30 mg/L for about 20 min, but 25 min of exposure caused deaths. For 15 min exposures, concentrations of 35 mg/L for chinook salmon and 40 mg/L for Atlantic salmon were lethal.

Anesthetic Concerns of Space Flight

NASA Technical Reports Server (NTRS)

Norfleet, William T.

1999-01-01

Anesthesiologists are acutely aware of the fact that, although a given surgical procedure may be relatively simple, the required anesthetic care is, in certain cases, extremely complex. This principle is particularly evident when one ponders the difficulties involved in providing even basic anesthetic care in microgravity. In this issue some of these difficulties through the evaluation of airway management techniques during water immersion are confronted, a simulation of the gravito-inertial conditions of space flight. As prelude for this paper, I would like to outline some of the challenges to be overcome before surgical, anesthetic, and critical care can be delivered beyond our home planet.

Surgical Approach and Anesthetic Modality for Carpal Tunnel Release: A Nationwide Database Study With Health Care Cost Implications.

PubMed

Foster, Brock D; Sivasundaram, Lakshmanan; Heckmann, Nathanael; Cohen, Jeremiah R; Pannell, William C; Wang, Jeffrey C; Ghiassi, Alidad

2017-03-01

Background: Carpal tunnel release (CTR) is commonly performed for carpal tunnel syndrome once conservative treatment has failed. Operative technique and anesthetic modality vary by surgeon preference and patient factors. However, CTR practices and anesthetic trends have, to date, not been described on a nationwide scale in the United States. Methods: The PearlDiver Patient Records Database was used to search Current Procedural Terminology codes for elective CTR from 2007 to 2011. Anesthetic modality (eg, general and regional anesthesia vs local anesthesia) and surgical approach (eg, endoscopic vs open) were recorded for this patient population. Cost analysis, patient demographics, regional variation, and annual changes in CTR surgery were evaluated. Results: We identified 86 687 patients who underwent carpal tunnel surgery during this 5-year time period. In this patient sample, 80.5% of CTR procedures were performed using general or regional anesthesia, compared with 19.5% of procedures performed using local anesthesia; 83.9% of all CTR were performed in an open fashion, and 16.1% were performed using an endoscopic technique. Endoscopic surgery was on average $794 more expensive than open surgery, and general or regional anesthesia was $654 more costly than local anesthesia. Conclusions: In the United States, open CTR under local anesthesia is the most cost-effective way to perform a CTR. However, only a small fraction of elective CTR procedures are performed with this technique, representing a potential area for significant health care cost savings. In addition, regional and age variations exist in procedure and anesthetic type utilized.

Methods to produce calibration mixtures for anesthetic gas monitors and how to perform volumetric calculations on anesthetic gases.

PubMed

Christensen, P L; Nielsen, J; Kann, T

1992-10-01

A simple procedure for making calibration mixtures of oxygen and the anesthetic gases isoflurane, enflurane, and halothane is described. One to ten grams of the anesthetic substance is evaporated in a closed, 11,361-cc glass bottle filled with oxygen gas at atmospheric pressure. The carefully mixed gas is used to calibrate anesthetic gas monitors. By comparison of calculated and measured volumetric results it is shown that at atmospheric conditions the volumetric behavior of anesthetic gas mixtures can be described with reasonable accuracy using the ideal gas law. A procedure is described for calculating the deviation from ideal gas behavior in cases in which this is needed.

Mutations M287L and Q266I in the Glycine Receptor α1 Subunit Change Sensitivity to Volatile Anesthetics in Oocytes and Neurons, but Not the Minimal Alveolar Concentration in Knockin Mice

PubMed Central

Borghese, Cecilia M.; Xiong, Wei; Oh, S. Irene; Ho, Angel; Mihic, S. John; Zhang, Li; Lovinger, David M.; Homanics, Gregg E.; Eger, Edmond I; Harris, R. Adron

2012-01-01

Background Volatile anesthetics (VAs) alter the function of key central nervous system proteins but it is not clear which, if any, of these targets mediates the immobility produced by VAs in the face of noxious stimulation. A leading candidate is the glycine receptor, a ligand-gated ion channel important for spinal physiology. VAs variously enhance such function, and blockade of spinal GlyRs with strychnine affects the minimal alveolar concentration (an anesthetic EC50) in proportion to the degree of enhancement. Methods We produced single amino acid mutations into the glycine receptorα1 subunit that increased (M287L, third transmembrane region) or decreased (Q266I, second transmembrane region) sensitivity to isoflurane in recombinant receptors, and introduced such receptors into mice. The resulting knockin mice presented impaired glycinergic transmission, but heterozygous animals survived to adulthood, and we determined the effect of isoflurane on glycine-evoked responses of brain stem neurons from the knockin mice, and the minimal alveolar concentration for isoflurane and other VAs in the immature and mature knockin mice. Results Studies of glycine-evoked currents in brain stem neurons from knock-in mice confirmed the changes seen with recombinant receptors. No increases in the minimal alveolar concentration were found in knockin mice, but the minimal alveolar concentration for isoflurane and enflurane (but not halothane) decreased in 2-week-old Q266I mice. This change is opposite to the one expected for a mutation that decreases the sensitivity to volatile anesthetics. Conclusion Taken together, these results indicate that glycine receptors containing the α1 subunit are not likely to be crucial for the action of isoflurane and other VAs. PMID:22885675

Ischemia-Reperfusion Injury and Volatile Anesthetics

PubMed Central

Erturk, Engin

2014-01-01

Ischemia-reperfusion injury (IRI) is induced as a result of reentry of the blood and oxygen to ischemic tissue. Antioxidant and some other drugs have protective effect on IRI. In many surgeries and clinical conditions IRI is counteract inevitable. Some anesthetic agents may have a protective role in this procedure. It is known that inhalational anesthetics possess protective effects against IRI. In this review the mechanism of preventive effects of volatile anesthetics and different ischemia-reperfusion models are discussed. PMID:24524079

Participation of the GABAergic system in the anesthetic effect of Lippia alba (Mill.) N.E. Brown essential oil

PubMed Central

Heldwein, C.G.; Silva, L.L.; Reckziegel, P.; Barros, F.M.C.; Bürger, M.E.; Baldisserotto, B.; Mallmann, C.A.; Schmidt, D.; Caron, B.O.; Heinzmann, B.M.

2012-01-01

The objective of this study was to identify the possible involvement of the GABAergic system in the anesthetic effect of Lippia alba essential oil (EO). We propose a new animal model using silver catfish (Rhamdia quelen) exposed to an anesthetic bath to study the mechanism of action of EO. To observe the induction and potentiation of the anesthetic effect of EO, juvenile silver catfish (9.30 ± 1.85 g; 10.15 ± 0.95 cm; N = 6) were exposed to various concentrations of L. alba EO in the presence or absence of diazepam [an agonist of high-affinity binding sites for benzodiazepinic (BDZ) sites coupled to the GABAA receptor complex]. In another experiment, fish (N = 6) were initially anesthetized with the EO and then transferred to an anesthetic-free aquarium containing flumazenil (a selective antagonist of binding sites for BDZ coupled to the GABAA receptor complex) or water to assess recovery time from the anesthesia. In this case, flumazenil was used to observe the involvement of the GABA-BDZ receptor in the EO mechanism of action. The results showed that diazepam potentiates the anesthetic effect of EO at all concentrations tested. Fish exposed to diazepam and EO showed faster recovery from anesthesia when flumazenil was added to the recovery bath (12.0 ± 0.3 and 7.2 ± 0.7, respectively) than those exposed to water (9.2 ± 0.2 and 3.5 ± 0.3, respectively). In conclusion, the results demonstrated the involvement of the GABAergic system in the anesthetic effect of L. alba EO on silver catfish. PMID:22473320

Development of three Drosophila melanogaster strains with different sensitivity to volatile anesthetics.

PubMed

Liu, Jin; Hu, Zhao-yang; Ye, Qi-quan; Dai, Shuo-hua

2009-03-05

The mechanisms of action for volatile anesthetics remain unknown for centuries partly owing to the insufficient or ineffective research models. We designed this study to develop three strains derived from a wild-type Drosophila melanogaster with different sensitivities to volatile anesthetics, which may ultimately facilitate molecular and genetic studies of the mechanism involved. Median effective doses (ED(50)) of sevoflurane in seven-day-old virgin female and male wild-type Drosophila melanogaster were determined. The sensitive males and females of percentile 6 - 10 were cultured for breeding sensitive offspring (S(1)). So did median ones of percentile 48 - 52 for breeding median offspring (M(1)), resistant ones of percentile 91 - 95 for breeding resistant offspring (R(1)). Process was repeated through 31 generations, in the 37th generation, S(37), M(37) and R(37) were used to determine ED(50) for enflurane, isoflurane, sevoflurane, desflurane, halothane, methoxyflurane, chloroform and trichloroethylene, then ED(50) values were correlated with minimum alveolar concentration (MAC) values in human. From a wild-type Drosophila melanogaster we were able to breed three strains with high, median and low sevoflurane requirements. The ratio of sevoflurane requirements of three strains were 1.20:1.00:0.53 for females and 1.22:1.00:0.72 for males. Strains sensitive, median and resistant to sevoflurane were also sensitive, median and resistant to other volatile anesthetics. For eight anesthetics, ED(50) values in three strains correlated directly with MAC values in human. Three Drosophila melanogaster strains with high, median and low sensitivity to volatile anesthetics, but with same hereditary background were developed. The ED(50) are directly correlated with MAC in human for eight volatile anesthetics.

Clinically Enhancing Local Anesthesia Techniques for Endodontic Treatment.

PubMed

Bahcall, James; Xie, Qian

2017-02-01

Local anesthesia is one of the most important drugs given to patients who undergo endodontic treatment. Yet, clinicians often do not view local anesthetic agents as drugs and, therefore, struggle clinically to consistently achieve profound pulpal anesthesia. To improve the clinical effects of local anesthesia for endodontic treatment, in conjunction with selecting the correct type of local anesthesia, clinicians need to thoroughly understand how the local anesthetic process works and how to objectively test for clinical signs of pulpal anesthesia and integrate supplemental anesthesia when appropriate.

A Unitary Anesthetic Binding Site at High Resolution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vedula, L. Sangeetha; Brannigan, Grace; Economou, Nicoleta J.

2009-10-21

Propofol is the most widely used injectable general anesthetic. Its targets include ligand-gated ion channels such as the GABA{sub A} receptor, but such receptor-channel complexes remain challenging to study at atomic resolution. Until structural biology methods advance to the point of being able to deal with systems such as the GABA{sub A} receptor, it will be necessary to use more tractable surrogates to probe the molecular details of anesthetic recognition. We have previously shown that recognition of inhalational general anesthetics by the model protein apoferritin closely mirrors recognition by more complex and clinically relevant protein targets; here we show thatmore » apoferritin also binds propofol and related GABAergic anesthetics, and that the same binding site mediates recognition of both inhalational and injectable anesthetics. Apoferritin binding affinities for a series of propofol analogs were found to be strongly correlated with the ability to potentiate GABA responses at GABA{sub A} receptors, validating this model system for injectable anesthetics. High resolution x-ray crystal structures reveal that, despite the presence of hydrogen bond donors and acceptors, anesthetic recognition is mediated largely by van der Waals forces and the hydrophobic effect. Molecular dynamics simulations indicate that the ligands undergo considerable fluctuations about their equilibrium positions. Finally, apoferritin displays both structural and dynamic responses to anesthetic binding, which may mimic changes elicited by anesthetics in physiologic targets like ion channels.« less

A Unitary Anesthetic Binding Site at High Resolution

DOE Office of Scientific and Technical Information (OSTI.GOV)

L Vedula; G Brannigan; N Economou

2011-12-31

Propofol is the most widely used injectable general anesthetic. Its targets include ligand-gated ion channels such as the GABA{sub A} receptor, but such receptor-channel complexes remain challenging to study at atomic resolution. Until structural biology methods advance to the point of being able to deal with systems such as the GABA{sub A} receptor, it will be necessary to use more tractable surrogates to probe the molecular details of anesthetic recognition. We have previously shown that recognition of inhalational general anesthetics by the model protein apoferritin closely mirrors recognition by more complex and clinically relevant protein targets; here we show thatmore » apoferritin also binds propofol and related GABAergic anesthetics, and that the same binding site mediates recognition of both inhalational and injectable anesthetics. Apoferritin binding affinities for a series of propofol analogs were found to be strongly correlated with the ability to potentiate GABA responses at GABA{sub A} receptors, validating this model system for injectable anesthetics. High resolution x-ray crystal structures reveal that, despite the presence of hydrogen bond donors and acceptors, anesthetic recognition is mediated largely by van der Waals forces and the hydrophobic effect. Molecular dynamics simulations indicate that the ligands undergo considerable fluctuations about their equilibrium positions. Finally, apoferritin displays both structural and dynamic responses to anesthetic binding, which may mimic changes elicited by anesthetics in physiologic targets like ion channels.« less

A Unitary Anesthetic-Binding Site at High Resolution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vedula, L.; Brannigan, G; Economou, N

2009-01-01

Propofol is the most widely used injectable general anesthetic. Its targets include ligand-gated ion channels such as the GABAA receptor, but such receptor-channel complexes remain challenging to study at atomic resolution. Until structural biology methods advance to the point of being able to deal with systems such as the GABA{sub A} receptor, it will be necessary to use more tractable surrogates to probe the molecular details of anesthetic recognition. We have previously shown that recognition of inhalational general anesthetics by the model protein apoferritin closely mirrors recognition by more complex and clinically relevant protein targets; here we show that apoferritinmore » also binds propofol and related GABAergic anesthetics, and that the same binding site mediates recognition of both inhalational and injectable anesthetics. Apoferritin binding affinities for a series of propofol analogs were found to be strongly correlated with the ability to potentiate GABA responses at GABA{sub A} receptors, validating this model system for injectable anesthetics. High resolution x-ray crystal structures reveal that, despite the presence of hydrogen bond donors and acceptors, anesthetic recognition is mediated largely by van der Waals forces and the hydrophobic effect. Molecular dynamics simulations indicate that the ligands undergo considerable fluctuations about their equilibrium positions. Finally, apoferritin displays both structural and dynamic responses to anesthetic binding, which may mimic changes elicited by anesthetics in physiologic targets like ion channels.« less

Local anesthetic and antiepileptic drug access and binding to a bacterial voltage-gated sodium channel

PubMed Central

Boiteux, Céline; Vorobyov, Igor; French, Robert J.; French, Christopher; Yarov-Yarovoy, Vladimir; Allen, Toby W.

2014-01-01

Voltage-gated sodium (Nav) channels are important targets in the treatment of a range of pathologies. Bacterial channels, for which crystal structures have been solved, exhibit modulation by local anesthetic and anti-epileptic agents, allowing molecular-level investigations into sodium channel-drug interactions. These structures reveal no basis for the “hinged lid”-based fast inactivation, seen in eukaryotic Nav channels. Thus, they enable examination of potential mechanisms of use- or state-dependent drug action based on activation gating, or slower pore-based inactivation processes. Multimicrosecond simulations of NavAb reveal high-affinity binding of benzocaine to F203 that is a surrogate for FS6, conserved in helix S6 of Domain IV of mammalian sodium channels, as well as low-affinity sites suggested to stabilize different states of the channel. Phenytoin exhibits a different binding distribution owing to preferential interactions at the membrane and water–protein interfaces. Two drug-access pathways into the pore are observed: via lateral fenestrations connecting to the membrane lipid phase, as well as via an aqueous pathway through the intracellular activation gate, despite being closed. These observations provide insight into drug modulation that will guide further developments of Nav inhibitors. PMID:25136136

A low dose of three local anesthetic solutions for interscalene blockade tested by thermal quantitative sensory testing: a randomized controlled trial.

PubMed

Sermeus, Luc A; Schepens, Tom; Hans, Guy H; Morrison, Stuart G; Wouters, Kristien; Breebaart, Margaretha B; Smitz, Carine J; Vercauteren, Marcel P

2018-05-03

This randomized double-blind controlled trial compared the block characteristics of three low-dose local anesthetics at different roots in an ultrasound-guided interscalene block, using thermal quantitative sensory testing for assessing the functioning of cutaneous small nerve fibres. A total of 37 adults scheduled to undergo shoulder arthroscopy were randomized to receive 5 mL of either 0.5% levobupivacaine with and without epinephrine 1/200,000 or 0.75% ropivacaine in a single-shot interscalene block. Thermal quantitative sensory testing was performed in the C4, C5, C6 and C7 dermatomes. Detection thresholds for cold/warm sensation and cold/heat pain were measured before and at 30 min, 6, 10 and 24 h after infiltration around C5. The need for rescue medication was recorded. No significant differences between groups were found for any sensation (lowest P = 0.28). At 6 h, the largest differences in sensory thresholds were observed for the C5 dermatome. The increase in thresholds were less in C4 and C6 and minimal in C7 for all sensations. The analgesic effect lasted the longest in C5 (time × location mixed model P < 0.001 for all sensory tests). The time to rescue analgesia was significantly shorter with 0.75% ropivacaine (P = 0.02). The quantitative sensory findings showed no difference in intensity between the local anesthetics tested. A decrease in block intensity, with minimal changes in pain detection thresholds, was observed in the roots adjacent to C5, with the lowest block intensity in C7. A clinically relevant shorter duration was found with 0.75% ropivacaine compared to the other groups. Trial registration NCT 02691442.

Development of An Assessment Test for An Anesthetic Machine.

PubMed

Tiviraj, Supinya; Yokubol, Bencharatana; Amornyotin, Somchai

2016-05-01

The study is aimed to develop and assess the quality of an evaluation form used to evaluate the nurse anesthetic trainees' skills in undertaking a pre-use check of an anesthetic machine. An evaluation form comprising 25 items was developed, informed by the guidelines published by national anesthesiologist societies and refined to reflect the anesthetic machine used in our institution. The item-checking included the cylinder supplies and medical gas pipelines, vaporizer back bar, ventilator anesthetic breathing system, scavenging system and emergency back-up equipment. The authors sought the opinions of five experienced anesthetic trainers to judge the validity of the content. The authors measured its inter-rater reliability when used by two achievement scores evaluating the performance of 36 nurse anesthetic trainees undertaking 15-minute anesthetic machine checks and test-retest the reliability correlation scores between the two performances in the seven days interval. The five experienced anesthesiologists agreed that the evaluation form accurately reflected the objectives of anesthetic machine checking, equating to an index of congruency of 1.00. The inter-rater reliability of the independent assessors scoring was 0.977 (p = 0.01) and the test-retest reliability was 0.883 (p = 0.01). An evaluation form proved to be a reliable and effective tool for assessing the anesthetic nurse trainees' checking of an anesthetic machine before the use. This evaluation form was brief clear and practical to use, and should help to improve anesthetic nurse education and the patient safety.

The use of the mandibular infiltration anesthetic technique in adults.

PubMed

Meechan, John G

2011-09-01

The author describes the use of the infiltration anesthetic technique to anesthetize mandibular teeth in adults and explores its mechanism of action. The author reviewed articles describing randomized controlled trials of the mandibular infiltration anesthetic technique in healthy participants. The author found that using the mandibular infiltration anesthetic technique can produce anesthesia in adult mandibular teeth. The success was dose dependent and the choice of anesthetic solution was significant; 4 percent articaine with 1:100,000 epinephrine was more effective than 2 percent lidocaine with 1:100,000 epinephrine. Combining buccal and lingual infiltrations increased success in the mandibular incisor region. The success of the mechanism of infiltration of anesthetic at the mandibular first molar appeared to depend on the mental foramen. The mandibular infiltration anesthetic technique is an effective method of anesthetizing mandibular incisors. Four percent articaine with epinephrine appears to be the preferred solution. The choice of anesthetic solution is important when using the infiltration anesthetic technique in the adult mandible.

Assessing anesthetic activity through modulation of the membrane dipole potential.

PubMed

Davis, Benjamin Michael; Brenton, Jonathan; Davis, Sterenn; Shamsher, Ehtesham; Sisa, Claudia; Grgic, Ljuban; Cordeiro, M Francesca

2017-10-01

There is great individual variation in response to general anesthetics (GAs) leading to difficulties in optimal dosing and sometimes even accidental awareness during general anesthesia (AAGA). AAGA is a rare, but potentially devastating, complication affecting between 0.1% and 2% of patients undergoing surgery. The development of novel personalized screening techniques to accurately predict a patient's response to GAs and the risk of AAGA remains an unmet clinical need. In the present study, we demonstrate the principle of using a fluorescent reporter of the membrane dipole potential, di-8-ANEPPs, as a novel method to monitor anesthetic activity using a well-described inducer/noninducer pair. The membrane dipole potential has previously been suggested to contribute a novel mechanism of anesthetic action. We show that the fluorescence ratio of di-8-ANEPPs changed in response to physiological concentrations of the anesthetic, 1-chloro-1,2,2-trifluorocyclobutane (F 3 ), but not the structurally similar noninducer, 1,2-dichlorohexafluorocyclobutane (F 6 ), to artificial membranes and in vitro retinal cell systems. Modulation of the membrane dipole provides an explanation to overcome the limitations associated with the alternative membrane-mediated mechanisms of GA action. Furthermore, by combining this technique with noninvasive retinal imaging technologies, we propose that this technique could provide a novel and noninvasive technique to monitor GA susceptibility and identify patients at risk of AAGA. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

Noninvasive investigation of skin local hypothermia influence upon local oxygenation and hemoglobin concentration

NASA Astrophysics Data System (ADS)

Douplik, Alexandre Y.; Kessler, Manfred D.; Kakihana, Yasuyuki; Krug, Alfons

1997-08-01

Functional evaluation of local hemoglobin concentration and hemoglobin oxygenation based on back scattering spectra from human skin in vivo have been obtained in visible range (502 - 628 nm) by a rapid microlightguide spectrometer (EMPHO II) with step 250 micrometer. Analysis of received results has shown that during local cooling there is two nearly simultaneous reactions: reduction of hemoglobin concentration and increase of hemoglobin oxygenation level. In a case when one has used previous heating of planning place for cooling, reduction of hemoglobin concentration is expressed higher by 22 - 33%.

Effect of anesthetics on the radiosensitivity of a murine tumor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sheldon, P.W.; Chu, A.M.

The effect of four anesthetics on the single dose of x rays required to locally control 50% of implanted MT tumors was investigated. Compared with unanesthetized animals, no change in radiosensitivity was observed if mice were irradiated under either tribromoethanol or fentanyl-fluanisone-diazepam anesthesia. However, a small but significant degree of radioprotection was observed under chloral hydrate or pentobarbital anesthesia. Hypothermia or increased hypoxia are considered unlikely mechanisms for the protection, a direct chemical action being most probable. The preferred method for immobilizing the mice in order to locally irradiate the tumors was by simple physical restraint (with care taken tomore » minimize physiological stress). However, if anesthesia was a necessity, the present work suggests that for the MT tumor at least the nonprotecting tribromoethanol and fentanyl-fluanisone-diazepam are preferable to the protecting chloral hydrate and pentobarbital. Tribromoethanol is preferable to fetanyl-fluanisone-diazepam in that it produces a smaller drop in temperature. However, it is only a short-acting anesthetic, and prolongation of the state of anesthesia by repeated doses simply prolongs the temperature decline so that there may be no real benefit over fentanyl-fluanisone-diazepam.« less

Anesthetics and red blood cell rheology

NASA Astrophysics Data System (ADS)

Aydogan, Burcu; Aydogan, Sami

2014-05-01

There are many conditions where it is useful for anesthetists to have a knowledge of blood rheology. Blood rheology plays an important role in numerous clinical situations. Hemorheologic changes may significantly affect the induction and recovery times with anesthetic agents. But also, hemorheologic factors are directly or indirectly affected by many anesthetic agents or their metabolites. In this review, the blood rheology with special emphasis on its application in anesthesiology, the importance hemorheological parameters in anesthesiology and also the effect of some anesthetic substances on red blood cell rheology were presented.

Ultra-long-duration local anesthesia produced by injection of lecithin-coated methoxyflurane microdroplets.

PubMed

Haynes, D H; Kirkpatrick, A F

1985-11-01

This study was designed to evaluate a new drug delivery system. The authors undertook to determine if microdroplets prepared by encapsulating volatile anesthetics with a membrane of lecithin could be used for local anesthesia. Local anesthesia was determined by monitoring the response of the rat to tail clamping and electrical stimulation of the skin following the intradermal injection of the microdroplets. Microdroplets were prepared from isoflurane, enflurane, halothane, methoxyflurane, diethyl ether, chloroform, and heptane. Although all microdroplet preparations produced local anesthesia, only methoxyflurane microdroplets produced an ultra-long duration of local anesthesia (approximately 24 h). Further characterization of the methoxyflurane microdroplets revealed two important differences from conventional local anesthetics. First, the local anesthetic effect of methoxyflurane reached a plateau that did not change significantly for 20 h while the injection of lidocaine and bupivacaine resulted in a peak effect that returned to baseline within 1 and 3 h, respectively. Second, the anesthetic effect of methoxyflurane remained essentially localized to the site of injection, while the anesthetic effect of lidocaine and bupivacaine migrated 15 cm in less than 1 h. The toxicity and safety of methoxyflurane were evaluated. When administered over the dosage range 1-16% (v/v) intradermally, or by injections into muscle, or by repeat injections every 4 days for 16 days, all animals regained their pretreatment response to painful stimulations, and there was no evidence of gross injury to tissue. Deliberate intravenous injection of 0.8 ml of 6.7% (v/v) methoxyflurane microdroplets had no apparent anesthetic or toxic effect. The present study demonstrates that methoxyflurane microdroplets produce an anesthetic effect that is highly localized, stable in intensity, ultra-long in duration, and reversible.

Effect of fluoroscopically guided caudal epidural steroid or local anesthetic injections in the treatment of lumbar disc herniation and radiculitis: a randomized, controlled, double blind trial with a two-year follow-up.

PubMed

Manchikanti, Laxmaiah; Singh, Vijay; Cash, Kimberly A; Pampati, Vidyasagar; Damron, Kim S; Boswell, Mark V

2012-01-01

Lumbar disc herniation and radiculitis are common elements of low back and lower extremity pain. Among minimally invasive treatments, epidural injections are one of the most commonly performed interventions. However, the literature is mixed about their effectiveness in managing low back and lower extremity pain. In general, individual studies and systematic reviews of epidural steroid injections have been hampered by their study design, baseline differences between treatment groups, inadequate sample sizes, highly controlled settings, lack of validated outcome measures, and the inability to confirm the injectate location because fluoroscopy was not used. A randomized, controlled, double blind, active control trial. A private, interventional pain management practice, specialty referral center in the United States. To assess the effectiveness of fluoroscopically directed caudal epidural injections with local anesthetic with or without steroids in managing chronic low back and lower extremity pain in patients with disc herniation and radiculitis. One hundred twenty patients were randomized to two groups: Group I received 10 mL caudal epidural injections of local anesthetic, lidocaine 0.5%; Group II patients received caudal epidural injections of 0.5% lidocaine, 9 mL, mixed with 1 mL of steroid. Multiple outcome measures were utilized. The primary outcome measures were Numeric Rating Scale (NRS) and the Oswestry Disability Index 2.0 (ODI). Secondary outcome measures were employment status and opioid intake. Significant pain relief improvement was defined as 50% or more improvement in NRS and ODI scores. In the successful category, 77% of Group I had significant pain relief of >/= 50% and functional status improvement of >/= 50% reduction in ODI scores; in Group II it was 76%, whereas overall it was 60% and 65% in Groups I and II. Over the two years, Group I had an average number of procedures of 5.5 ± 2.8; Group II was 5.3 ± 2.4. Even though there was no significant

Allyl m-Trifluoromethyldiazirine Mephobarbital: An Unusually Potent Enantioselective and Photoreactive Barbiturate General Anesthetic

DOE Office of Scientific and Technical Information (OSTI.GOV)

Savechenkov, Pavel Y.; Zhang, Xi; Chiara, David C.

2012-12-10

We synthesized 5-allyl-1-methyl-5-(m-trifluoromethyl-diazirynylphenyl)barbituric acid (14), a trifluoromethyldiazirine-containing derivative of general anesthetic mephobarbital, separated the racemic mixture into enantiomers by chiral chromatography, and determined the configuration of the (+)-enantiomer as S by X-ray crystallography. Additionally, we obtained the {sup 3}H-labeled ligand with high specific radioactivity. R-(-)-14 is an order of magnitude more potent than the most potent clinically used barbiturate, thiopental, and its general anesthetic EC{sub 50} approaches those for propofol and etomidate, whereas S-(+)-14 is 10-fold less potent. Furthermore, at concentrations close to its anesthetic potency, R-(-)-14 both potentiated GABA-induced currents and increased the affinity for the agonist muscimol inmore » human {alpha}1{beta}2/3{gamma}2L GABA{sub A} receptors. Finally, R-(-)-14 was found to be an exceptionally efficient photolabeling reagent, incorporating into both {alpha}1 and {beta}3 subunits of human {alpha}1{beta}3 GABAA receptors. These results indicate R-(-)-14 is a functional general anesthetic that is well-suited for identifying barbiturate binding sites on Cys-loop receptors.« less

The Differential Effects of Anesthetics on Bacterial Behaviors

PubMed Central

Chamberlain, Matthew; Koutsogiannaki, Sophia; Schaefers, Matthew; Babazada, Hasan; Liu, Renyu; Yuki, Koichi

2017-01-01

Volatile anesthetics have been in clinical use for a long period of time and are considered to be promiscuous by presumably interacting with several ion channels in the central nervous system to produce anesthesia. Because ion channels and their existing evolutionary analogues, ion transporters, are very important in various organisms, it is possible that volatile anesthetics may affect some bacteria. In this study, we hypothesized that volatile anesthetics could affect bacterial behaviors. We evaluated the impact of anesthetics on bacterial growth, motility (swimming and gliding) and biofilm formation of four common bacterial pathogens in vitro. We found that commonly used volatile anesthetics isoflurane and sevoflurane affected bacterial motility and biofilm formation without any effect on growth of the common bacterial pathogens studied here. Using available Escherichia coli gene deletion mutants of ion transporters and in silico molecular docking, we suggested that these altered behaviors might be at least partly via the interaction of volatile anesthetics with ion transporters. PMID:28099463

Discrete change in volatile anesthetic sensitivity in mice with inactivated tandem pore potassium ion channel TRESK.

PubMed

Chae, Yun Jeong; Zhang, Jianan; Au, Paul; Sabbadini, Marta; Xie, Guo-Xi; Yost, C Spencer

2010-12-01

We investigated the role of tandem pore potassium ion channel (K2P) TRESK in neurobehavioral function and volatile anesthetic sensitivity in genetically modified mice. Exon III of the mouse TRESK gene locus was deleted by homologous recombination using a targeting vector. The genotype of bred mice (wild type, knockout, or heterozygote) was determined using polymerase chain reaction. Morphologic and behavioral evaluations of TRESK knockout mice were compared with wild-type littermates. Sensitivity of bred mice to isoflurane, halothane, sevoflurane, and desflurane were studied by determining the minimum alveolar concentration preventing movement to tail clamping in 50% of each genotype. With the exception of decreased number of inactive periods and increased thermal pain sensitivity (20% decrease in latency with hot plate test), TRESK knockout mice had healthy development and behavior. TRESK knockout mice showed a statistically significant 8% increase in isoflurane minimum alveolar concentration compared with wild-type littermates. Sensitivity to other volatile anesthetics was not significantly different. Spontaneous mortality of TRESK knockout mice after initial anesthesia testing was nearly threefold higher than that of wild-type littermates. TRESK alone is not critical for baseline central nervous system function but may contribute to the action of volatile anesthetics. The inhomogeneous change in anesthetic sensitivity corroborates findings in other K2P knockout mice and supports the theory that the mechanism of volatile anesthetic action involves multiple targets. Although it was not shown in this study, a compensatory effect by other K2P channels may also contribute to these observations.

Mass spectrometry method to monitor the sevoflurane concentration in an apparatus for inhalational anesthesia

NASA Astrophysics Data System (ADS)

Elokhin, V. A.; Ershov, T. D.; Levshankov, A. I.; Nikolaev, V. I.; Saifullin, M. F.; Elizarov, A. Yu.

2010-08-01

The feasibility of real-time monitoring of the inhalational anesthetic (sevoflurane) concentration in the respiratory circuit of an apparatus for inhalational anesthesia using mass spectrometry is considered. It is shown that the absolute anesthetic concentration can be monitored in real time if low-flow ventilation is provided during general anesthesia. The time dependences of the anesthetic concentration are taken at different stages of anesthesia in the inspiration-expiration regime.

Awake craniotomy anesthetic management using dexmedetomidine, propofol, and remifentanil

PubMed Central

Prontera, Andrea; Baroni, Stefano; Marudi, Andrea; Valzania, Franco; Feletti, Alberto; Benuzzi, Francesca; Bertellini, Elisabetta; Pavesi, Giacomo

2017-01-01

Introduction Awake craniotomy allows continuous monitoring of patients’ neurological functions during open surgery. Anesthesiologists have to sedate patients in a way so that they are compliant throughout the whole surgical procedure, nevertheless maintaining adequate analgesia and anxiolysis. Currently, the use of α2-receptor agonist dexmedetomidine as the primary hypnotic–sedative medication is increasing. Methods Nine patients undergoing awake craniotomy were treated with refined monitored anesthesia care (MAC) protocol consisting of a combination of local anesthesia without scalp block, low-dose infusion of dexmedetomidine, propofol, and remifentanil, without the need of airways management. Results The anesthetic protocol applied in our study has the advantage of decreasing the dose of each drug and thus reducing the occurrence of side effects. All patients had smooth and rapid awakenings. The brain remained relaxed during the entire procedure. Conclusion In our experience, this protocol is safe and effective during awake brain surgery. Nevertheless, prospective randomized trials are necessary to confirm the optimal anesthetic technique to be used. PMID:28424537

Awake craniotomy anesthetic management using dexmedetomidine, propofol, and remifentanil.

PubMed

Prontera, Andrea; Baroni, Stefano; Marudi, Andrea; Valzania, Franco; Feletti, Alberto; Benuzzi, Francesca; Bertellini, Elisabetta; Pavesi, Giacomo

2017-01-01

Awake craniotomy allows continuous monitoring of patients' neurological functions during open surgery. Anesthesiologists have to sedate patients in a way so that they are compliant throughout the whole surgical procedure, nevertheless maintaining adequate analgesia and anxiolysis. Currently, the use of α2-receptor agonist dexmedetomidine as the primary hypnotic-sedative medication is increasing. Nine patients undergoing awake craniotomy were treated with refined monitored anesthesia care (MAC) protocol consisting of a combination of local anesthesia without scalp block, low-dose infusion of dexmedetomidine, propofol, and remifentanil, without the need of airways management. The anesthetic protocol applied in our study has the advantage of decreasing the dose of each drug and thus reducing the occurrence of side effects. All patients had smooth and rapid awakenings. The brain remained relaxed during the entire procedure. In our experience, this protocol is safe and effective during awake brain surgery. Nevertheless, prospective randomized trials are necessary to confirm the optimal anesthetic technique to be used.

Anesthetic effects in Alzheimer transgenic mouse models.

PubMed

Tang, Junxia X; Eckenhoff, Maryellen F

2013-12-02

Research has improved the diagnosis of Alzheimer's disease, and at earlier stages, but effective therapy continues to be elusive. Current effort is focused on delay. Environmental factors are thought to interact with genetics to modulate the progression of the disease, and one such environmental factor is exposure to general anesthetics. The possibility that some anesthetic effects have long-term consequences is of general interest and concern. The difficulty of studying a chronic, age-related disease in humans combined with the fact that anesthetics are rarely given without surgery, has led to a focus on animal models. Transgenic mouse models have been developed to mimic the hallmarks of Alzheimer's disease, including amyloid beta accumulation (plaque), neurofibrillary tangles, and cognitive dysfunction. While none of the models recapitulate the human disease with high fidelity, they allow a first look at anesthetic-Alzheimer interactions in a reasonable time frame. In studies found to date, none have concluded that anesthetics alone cause a significant change in cognitive decline, but rather an acceleration in Alzheimer neuropathology. Further studies are required to define the best anesthetic paradigm for our elderly population to mitigate changes in neuropathology and potentially cognition. Copyright © 2012 Elsevier Inc. All rights reserved.

Atomistic Models of General Anesthetics for Use in in Silico Biological Studies

PubMed Central

2015-01-01

While small molecules have been used to induce anesthesia in a clinical setting for well over a century, a detailed understanding of the molecular mechanism remains elusive. In this study, we utilize ab initio calculations to develop a novel set of CHARMM-compatible parameters for the ubiquitous modern anesthetics desflurane, isoflurane, sevoflurane, and propofol for use in molecular dynamics (MD) simulations. The parameters generated were rigorously tested against known experimental physicochemical properties including dipole moment, density, enthalpy of vaporization, and free energy of solvation. In all cases, the anesthetic parameters were able to reproduce experimental measurements, signifying the robustness and accuracy of the atomistic models developed. The models were then used to study the interaction of anesthetics with the membrane. Calculation of the potential of mean force for inserting the molecules into a POPC bilayer revealed a distinct energetic minimum of 4–5 kcal/mol relative to aqueous solution at the level of the glycerol backbone in the membrane. The location of this minimum within the membrane suggests that anesthetics partition to the membrane prior to binding their ion channel targets, giving context to the Meyer–Overton correlation. Moreover, MD simulations of these drugs in the membrane give rise to computed membrane structural parameters, including atomic distribution, deuterium order parameters, dipole potential, and lateral stress profile, that indicate partitioning of anesthetics into the membrane at the concentration range studied here, which does not appear to perturb the structural integrity of the lipid bilayer. These results signify that an indirect, membrane-mediated mechanism of channel modulation is unlikely. PMID:25303275

The Molecular Mechanisms of Anesthetic Action: Updates and Cutting Edge Developments from the Field of Molecular Modeling.

PubMed

Bertaccini, Edward J

2010-07-08

For over 160 years, general anesthetics have been given for the relief of pain and suffering. While many theories of anesthetic action have been purported, it has become increasingly apparent that a significant molecular focus of anesthetic action lies within the family of ligand-gated ion channels (LGIC's). These protein channels have a transmembrane region that is composed of a pentamer of four helix bundles, symmetrically arranged around a central pore for ion passage. While initial and some current models suggest a possible cavity for binding within this four helix bundle, newer calculations postulate that the actual cavity for anesthetic binding may exist between four helix bundles. In either scenario, these cavities have a transmembrane mode of access and may be partially bordered by lipid moieties. Their physicochemical nature is amphiphilic. Anesthetic binding may alter the overall motion of a ligand-gated ion channel by a "foot-in-door" motif, resulting in the higher likelihood of and greater time spent in a specific channel state. The overall gating motion of these channels is consistent with that shown in normal mode analyses carried out both in vacuo as well as in explicitly hydrated lipid bilayer models. Molecular docking and large scale molecular dynamics calculations may now begin to show a more exact mode by which anesthetic molecules actually localize themselves and bind to specific protein sites within LGIC's, making the design of future improvements to anesthetic ligands a more realizable possibility.

Endothelial barrier protection by local anesthetics: ropivacaine and lidocaine block tumor necrosis factor-α-induced endothelial cell Src activation.

PubMed

Piegeler, Tobias; Votta-Velis, E Gina; Bakhshi, Farnaz R; Mao, Mao; Carnegie, Graeme; Bonini, Marcelo G; Schwartz, David E; Borgeat, Alain; Beck-Schimmer, Beatrice; Minshall, Richard D

2014-06-01

Pulmonary endothelial barrier dysfunction mediated in part by Src-kinase activation plays a crucial role in acute inflammatory disease. Proinflammatory cytokines, such as tumor necrosis factor-α (TNFα), activate Src via phosphatidylinositide 3-kinase/Akt-dependent nitric oxide generation, a process initiated by recruitment of phosphatidylinositide 3-kinase regulatory subunit p85 to TNF-receptor-1. Because amide-linked local anesthetics have well-established anti-inflammatory effects, the authors hypothesized that ropivacaine and lidocaine attenuate inflammatory Src signaling by disrupting the phosphatidylinositide 3-kinase-Akt-nitric oxide pathway, thus blocking Src-dependent neutrophil adhesion and endothelial hyperpermeability. Human lung microvascular endothelial cells, incubated with TNFα in the absence or presence of clinically relevant concentrations of ropivacaine and lidocaine, were analyzed by Western blot, probing for phosphorylated/activated Src, endothelial nitric oxide synthase, Akt, intercellular adhesion molecule-1, and caveolin-1. The effect of ropivacaine on TNFα-induced nitric oxide generation, co-immunoprecipitation of TNF-receptor-1 with p85, neutrophil adhesion, and endothelial barrier disruption were assessed. Ropivacaine and lidocaine attenuated TNFα-induced Src activation (half-maximal inhibitory concentration [IC50] = 8.611 × 10 M for ropivacaine; IC50 = 5.864 × 10 M for lidocaine) and endothelial nitric oxide synthase phosphorylation (IC50 = 7.572 × 10 M for ropivacaine; IC50 = 6.377 × 10 M for lidocaine). Akt activation (n = 7; P = 0.006) and stimulus-dependent binding of TNF-receptor-1 and p85 (n = 6; P = 0.043) were blocked by 1 nM of ropivacaine. TNFα-induced neutrophil adhesion and disruption of endothelial monolayers via Src-dependent intercellular adhesion molecule-1- and caveolin-1-phosphorylation, respectively, were also attenuated. Ropivacaine and lidocaine effectively blocked inflammatory TNFα signaling in endothelial

Cellular mechanisms against ischemia reperfusion injury induced by the use of anesthetic pharmacological agents.

PubMed

Álvarez, P; Tapia, L; Mardones, L A; Pedemonte, J C; Farías, J G; Castillo, R L

2014-07-25

Ischemia-reperfusion (IR) cycle in the myocardium is associated with activation of an injurious cascade, thus leading to new myocardial challenges, which account for up to 50% of infarct size. Some evidence implicates reactive oxygen species (ROS) as a probable cause of myocardial injury in prooxidant clinical settings. Damage occurs during both ischemia and post-ischemic reperfusion in animal and human models. The mechanisms that contribute to this damage include the increase in cellular calcium (Ca(2+)) concentration and induction of ROS sources during reperfusion. Pharmacological preconditioning, which includes pharmacological strategies that counteract the ROS burst and Ca(2+) overload followed to IR cycle in the myocardium, could be effective in limiting injury. Currently widespread evidence supports the use of anesthetics agents as an important cardioprotective strategy that act at various levels such as metabotropic receptors, ion channels or mitochondrial level. Their administration before a prolonged ischemic episode is known as anesthetic preconditioning, whereas when given at the very onset of reperfusion, is termed anesthetic postconditioning. Both types of anesthetic conditioning reduce, albeit not to the same degree, the extent of myocardial injury. This review focuses on cellular and pathophysiological concepts on the myocardial damage induced by IR and how anesthetic pharmacological agents commonly used could attenuate the functional and structural effects induced by oxidative stress in cardiac tissue. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

S-(+)-Linalool from Lippia alba: sedative and anesthetic for silver catfish (Rhamdia quelen).

PubMed

Heldwein, Clarissa G; Silva, Lenise de L; Gai, Eduarda Z; Roman, Cassiela; Parodi, Thaylise V; Bürger, Marilise E; Baldisserotto, Bernardo; Flores, Érico M de M; Heinzmann, Berta M

2014-11-01

The present study describes the isolation of linalool from the essential oil of Lippia alba (Mill.) N. E. Brown, and its anesthetic effect in silver catfish (Rhamdia quelen) in comparison with essential oil. The potentiation of depressant effects of linalool with a benzodiazepine (BDZ) and the involvement of GABAergic system in its antagonism by flumazenil were also evaluated. Prospective experimental study. Juvenile silver catfish unknown sex weighing mean 9.24 ± 2.83 g (n = 6 for each experimental group per experiment). Column chromatography was used for the isolation of S-(+)-linalool. Fish (n = 6 for each concentration) were transferred to aquaria with linalool (30, 60, and 180 μL L(-1)) or EO of L. alba (50, 100, and 300 μL L(-1)) to determine the induction time for anesthesia. After induction, the animals were transferred to anesthetic-free aquaria to assess their recovery time. To observe the potentiation, fish were exposed to linalool (30, 60, and 180 μL L(-1)) in the presence or absence of BDZ (diazepam 150 μm). In another experiment, fish exposed to linalool (30 and 180 μL L(-1) or BDZ were transferred to an anesthetic-free aquaria containing flumazenil (5 μm) or water to assess recovery time. Linalool had a similar sedation profile to the essential oil at a proportional concentration in silver catfish. However, the anesthesia profile was different. Potentiation of linalool effect occurred only when tested at low concentration. Fish exposed to BDZ showed faster anesthesia recovery in water with flumazenil, but the same did not occur with linalool. The use of linalool as a sedative and anesthetic for silver catfish was effective at 30 and 180 μL L(-1), respectively. The mechanism of action seems not to involve the benzodiazepine site of the GABAergic system. © 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

Does anesthetic regimen influence implicit memory during general anesthesia?

PubMed

Lequeux, Pierre-Yves; Hecquet, Fidelie; Bredas, Philippe

2014-11-01

Implicit learning of intraoperative auditory stimuli during general anesthesia is very difficult to quantify but may require the presence of noxious stimulation. We hypothesized that an anesthetic regimen with a low dose of opioid would enhance implicit memory, while a regimen with a high dose of opioid would not. One hundred-twenty patients were randomized into 3 groups. All patients were anesthetized with a target-controlled infusion of propofol and remifentanil, targeting a Bispectral Index (BIS) value of 50. The remifentanil effect-site concentration (in ng/mL) was always double that of propofol (in μg/mL) in the first group and half of that in the second group. Patients in these 2 groups were played a list of 20 words via headphones during surgery. The third group served as control for memory tests and was not played any word during anesthesia. BIS was recorded during word presentation. No statistical difference was found among the 3 groups regarding 3 different memory tests although 67.5% [50.7%; 80.9%] of the patients of the high-opioid group and 72.5% [55.9%; 84.9%] of the low-opioid group had at least 1 episode of BIS >60. We could not demonstrate the presence of implicit or explicit memorization under propofol-remifentanil anesthesia either with a low- or a high-dose opioid anesthetic regimen.

NMR resolved multiple anesthetic binding sites in the TM domains of the α4β2 nAChR

PubMed Central

Bondarenko, Vasyl; Mowrey, David; Liu, Lu Tian; Xu, Yan; Tang, Pei

2012-01-01

The α4β2 nicotinic acetylcholine receptor (nAChR) has significant roles in nervous system function and disease. It is also a molecular target of general anesthetics. Anesthetics inhibit the α4β2 nAChR at clinically relevant concentrations, but their binding sites in α4β2 remain unclear. The recently determined NMR structures of the α4β2 nAChR transmembrane (TM) domains provide valuable frameworks for identifying the binding sites. In this study, we performed solution NMR experiments on the α4β2 TM domains in the absence and presence of halothane and ketamine. Both anesthetics were found in an intra-subunit cavity near the extracellular end of the 2 transmembrane helices, homologous to a common anesthetic binding site observed in X-ray structures of anesthetic-bound GLIC (Nury, et. al. 2011). Halothane, but not ketamine, was also found in cavities adjacent to the common anesthetic site at the interface of α4 and β2. In addition, both anesthetics bound to cavities near the ion selectivity filter at the intracellular end of the TM domains. Anesthetic binding induced profound changes in protein conformational exchanges. A number of residues, close to or remote from the binding sites, showed resonance signal splitting from single to double peaks, signifying that anesthetics decreased conformation exchange rates. It was also evident that anesthetics shifted population of two conformations. Altogether, the study comprehensively resolved anesthetic binding sites in the α4β2 nAChR. Furthermore, the study provided compelling experimental evidence of anesthetic-induced changes in protein dynamics, especially near regions of the hydrophobic gate and ion selectivity filter that directly regulate channel functions. PMID:23000369

NMR resolved multiple anesthetic binding sites in the TM domains of the α4β2 nAChR.

PubMed

Bondarenko, Vasyl; Mowrey, David; Liu, Lu Tian; Xu, Yan; Tang, Pei

2013-02-01

The α4β2 nicotinic acetylcholine receptor (nAChR) has significant roles in nervous system function and disease. It is also a molecular target of general anesthetics. Anesthetics inhibit the α4β2 nAChR at clinically relevant concentrations, but their binding sites in α4β2 remain unclear. The recently determined NMR structures of the α4β2 nAChR transmembrane (TM) domains provide valuable frameworks for identifying the binding sites. In this study, we performed solution NMR experiments on the α4β2 TM domains in the absence and presence of halothane and ketamine. Both anesthetics were found in an intra-subunit cavity near the extracellular end of the β2 transmembrane helices, homologous to a common anesthetic binding site observed in X-ray structures of anesthetic-bound GLIC (Nury et al., [32]). Halothane, but not ketamine, was also found in cavities adjacent to the common anesthetic site at the interface of α4 and β2. In addition, both anesthetics bound to cavities near the ion selectivity filter at the intracellular end of the TM domains. Anesthetic binding induced profound changes in protein conformational exchanges. A number of residues, close to or remote from the binding sites, showed resonance signal splitting from single to double peaks, signifying that anesthetics decreased conformation exchange rates. It was also evident that anesthetics shifted population of two conformations. Altogether, the study comprehensively resolved anesthetic binding sites in the α4β2 nAChR. Furthermore, the study provided compelling experimental evidence of anesthetic-induced changes in protein dynamics, especially near regions of the hydrophobic gate and ion selectivity filter that directly regulate channel functions. Copyright © 2012 Elsevier B.V. All rights reserved.

Direct Activation of Sleep-Promoting VLPO Neurons by Volatile Anesthetics Contributes to Anesthetic Hypnosis

PubMed Central

Moore, Jason T; Chen, Jingqiu; Han, Bo; Meng, Qing Cheng; Veasey, Sigrid C; Beck, Sheryl G; Kelz, Max B

2013-01-01

Summary Background Despite seventeen decades of continuous clinical use, the neuronal mechanisms through which volatile anesthetics act to produce unconsciousness remain obscure. One emerging possibility is that anesthetics exert their hypnotic effects by hijacking endogenous arousal circuits. A key sleep-promoting component of this circuitry is the ventrolateral preoptic nucleus (VLPO), a hypothalamic region containing both state-independent neurons and neurons that preferentially fire during natural sleep. Results Using c-Fos immunohistochemistry as a biomarker for antecedent neuronal activity, we show that isoflurane and halothane increase the number of active neurons in the VLPO, but only when mice are sedated or unconscious. Destroying VLPO neurons produces an acute resistance to isoflurane-induced hypnosis. Electrophysiological studies prove that the neurons depolarized by isoflurane belong to the subpopulation of VLPO neurons responsible for promoting natural sleep, while neighboring non-sleep-active VLPO neurons are unaffected by isoflurane. Finally, we show that this anesthetic-induced depolarization is not solely due to a presynaptic inhibition of wake-active neurons as previously hypothesized, but rather is due to a direct postsynaptic effect on VLPO neurons themselves arising from the closing of a background potassium conductance. Conclusions Cumulatively, this work demonstrates that anesthetics are capable of directly activating endogenous sleep-promoting networks and that such actions contribute to their hypnotic properties. PMID:23103189

Direct activation of sleep-promoting VLPO neurons by volatile anesthetics contributes to anesthetic hypnosis.

PubMed

Moore, Jason T; Chen, Jingqiu; Han, Bo; Meng, Qing Cheng; Veasey, Sigrid C; Beck, Sheryl G; Kelz, Max B

2012-11-06

Despite seventeen decades of continuous clinical use, the neuronal mechanisms through which volatile anesthetics act to produce unconsciousness remain obscure. One emerging possibility is that anesthetics exert their hypnotic effects by hijacking endogenous arousal circuits. A key sleep-promoting component of this circuitry is the ventrolateral preoptic nucleus (VLPO), a hypothalamic region containing both state-independent neurons and neurons that preferentially fire during natural sleep. Using c-Fos immunohistochemistry as a biomarker for antecedent neuronal activity, we show that isoflurane and halothane increase the number of active neurons in the VLPO, but only when mice are sedated or unconscious. Destroying VLPO neurons produces an acute resistance to isoflurane-induced hypnosis. Electrophysiological studies prove that the neurons depolarized by isoflurane belong to the subpopulation of VLPO neurons responsible for promoting natural sleep, whereas neighboring non-sleep-active VLPO neurons are unaffected by isoflurane. Finally, we show that this anesthetic-induced depolarization is not solely due to a presynaptic inhibition of wake-active neurons as previously hypothesized but rather is due to a direct postsynaptic effect on VLPO neurons themselves arising from the closing of a background potassium conductance. Cumulatively, this work demonstrates that anesthetics are capable of directly activating endogenous sleep-promoting networks and that such actions contribute to their hypnotic properties. Copyright © 2012 Elsevier Ltd. All rights reserved.

A clinical study to evaluate the efficacy of ELA-Max (4% liposomal lidocaine) as compared with eutectic mixture of local anesthetics cream for pain reduction of venipuncture in children.

PubMed

Eichenfield, Lawrence F; Funk, Ann; Fallon-Friedlander, Sheila; Cunningham, Bari B

2002-06-01

A double-randomized, blinded crossover trial was performed to assess the efficacy of ELA-Max (4% liposomal lidocaine) as compared with eutectic mixture of local anesthetics (EMLA) for pain relief during pediatric venipuncture procedures. Safety was assessed by evaluation for topical or systemic effects and measurement of serum lidocaine concentrations. A total of 120 children who were scheduled for repeat venipuncture for non-study-related reasons at 2 sites participated in the study. Patients were doubly randomized to treatment regimen (study medication application time of either 30 or 60 minutes) and to the order of application of the topical anesthetics for each venipuncture. The primary outcome measures were the child's rating of pain immediately after the venipuncture procedures using a 100-mm visual analog scale (VAS) tool and the parent's and blinded research observer's Observed Behavioral Distress scores. Both ELA-Max and EMLA seemed to alleviate venipuncture pain. There was no clinically or statistically significant difference in the patient VAS scores within the 30-minute or 60-minute treatment groups, and there was no clinical or statistical difference in VAS scores between the 30-minute ELA-Max treatment without occlusion and the 60-minute EMLA treatment with occlusion. There were no clinically or statistically significant differences between treatment with ELA-Max and EMLA in parental or blinded researcher Observed Behavioral Distress scores, the most frequent response at any observation time being "no distress." This study demonstrates that a 30-minute application of ELA-Max without occlusion is as safe and as effective for ameliorating pain associated with venipuncture as a 60-minute application of the prescription product EMLA requiring occlusion.

The effect of anesthetization and urinary bladder catheterization on renal function of rainbow trout

USGS Publications Warehouse

Hunn, J.B.; Willford, W.A.

1970-01-01

1. Rainbow trout were anesthetized with MS-222 (Sandoz) or methylpentynol and catheterized. Urine was collected at selected intervals up to 48 hr. 2. Effects of MS-222 anesthesia on urine flow and composition were isolated from the stress of catheterization by re-anesthetizing the fish 18 to 20 hr post catheterization. 3. Urine output patterns were similar following MS-222 or methylpentynol anesthesia and catheterization. Highest urine flows were measured 4 to 8 hr post treatment. The highest urine output after re-anesthetization with MS-222 was observed 2 to 4 hr post-anesthesia. 4. Highest concentrations of Na2+, K+, Ca2+, Cl- and inorganic PO4 in the urine were measured in the first 2 hr after anesthesia and catheterization. 5. Flow rates and chemical composition of urine indicate that "normal" renal function is re-established 12 to 24 hr post-treatment.

Analgesic effect of intraperitoneal local anesthetic in surgery: an overview of systematic reviews.

PubMed

Hamill, James K; Rahiri, Jamie-Lee; Hill, Andrew G

2017-05-15

Intraperitoneal local anesthetic (IPLA) reduces postoperative pain as shown by previous systematic reviews. The purpose of this review was to compare the efficacy of IPLA between different types of procedure and to formulate GRADE recommendations for the use of IPLA. A systematic search for systematic reviews of the effect of IPLA, versus no IPLA or placebo, on pain after any surgical procedure. Databases included in the study were MEDLINE, EMBASE, CDSR, and DARE. Two reviewers independently undertook searches, selected studies, extracted data, and assessed the risk of bias. Meta-analysis was by random effects. Recommendation was by GRADE. The main outcome measure was self-reported early postoperative pain scores. Searches uncovered nine systematic reviews. This study included randomized trials numbered 76, representing 4000 participants, 2022 in IPLA and 1978 in control groups. Six reviews scored at low risk of bias and three at high risk. Meta-analysis demonstrated that IPLA reduced the mean pain score (0-10 scale) by 0.95 point (95% confidence interval: 0.73-1.17). Excluding laparoscopic cholecystectomy, the effect size increased to 1.52 (95% confidence interval: 1.15-1.88). Heterogeneity was high overall at I 2  = 91.7% but on excluding laparoscopic cholecystectomy trials reduced to I 2  = 31.3%. IPLA could be considered a viable option for early postoperative analgesia in certain laparoscopic operations. Further research on the effect of IPLA on procedures other than laparoscopic cholecystectomy would help clarify its place in a postoperative analgesia protocol. Copyright © 2017 Elsevier Inc. All rights reserved.

Local anesthetics injection therapy for musculoskeletal disorders: a systematic review and meta-analysis.

PubMed

Mosshammer, Dirk; Mayer, Benjamin; Joos, Stefanie

2013-06-01

Therapeutic injections with local anesthetics (TLA) are widespread and are used for various symptoms of the musculoskeletal system. The aim of the present project was to evaluate the efficacy and safety of TLA in the treatment of musculoskeletal disorders. Systematic literature search for controlled clinical trials (Medline, Cochrane, CAMbase, hand search of references) without language limitation; independent screening of the search results (n=3200 hits), abstract reading, and full-text analysis by 2 reviewers. Two authors independently extracted the data and assessed study quality. Meta-analysis was calculated for studies using a continuous scale for pain assessment. Twenty-four controlled trials were included in this review. In almost all studies no primary outcome measure was defined and the overall study quality was low. The qualitative data analysis revealed no clear trend for or against TLA. The meta-analysis of 12 studies showed no significant difference in pain reduction for TLA compared with control treatments consisting of saline injections or other substances, oral analgesics, or nonpharmacological interventions (standardized mean difference -0.31, 95% confidence interval, -0.75 to 0.14). Minor adverse side effects were reported in 7 studies in both the TLA and the control groups with no trend for one of the groups to be safer. Despite the widespread use of TLA for musculoskeletal disorders in daily practice, available data are sparse and of low quality and, therefore, do not allow a final recommendation. High-quality studies are needed to close the gap between common practice and research.

Real-time measurement and control of waste anesthetic gases during veterinary surgeries

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burkhart, J.E.; Stobbe, T.J.

1990-12-01

Veterinary clinics are typically small businesses without access to sophisticated occupational safety and health programs that may exist for larger firms or hospitals. Exposures to waste anesthetic gases have been linked to a myriad of adverse health-related conditions. Excessive exposures to anesthetic agents are possible because many of the clinics use portable gas delivery carts that are not designed to capture waste gases. While scavenging systems are available to remove waste anesthetic gases, the cost may be prohibitive for smaller clinics and the effectiveness of these systems has not been fully established in veterinary clinics. The National Institute for Occupationalmore » Safety and Health (NIOSH) recommends limiting exposures to nitrous oxide (N2O) to a time-weighted average (TWA) concentration of 25 ppm and halogenated agents to 2 ppm. The NIOSH TWA is based on the weight of the agent collected from a 45-L air sample by charcoal adsorption over a sampling period not to exceed 1 hr. The NIOSH criteria state that, in most situations, control of N2O to the TWA as defined will result in levels of approximately 0.5 ppm of the halogenated agent. At present, no Occupational Safety and Health Administration (OSHA) permissible exposure level (PEL) exists for exposure to anesthetic agents; nor do specific recommendations exist for veterinary scavenging systems. Waste anesthetic gas exposures were determined using a modified MIRAN 1A at five veterinary clinics operating within the Morgantown, West Virginia, vicinity. For unscavenged systems of methoxyflurane and halothane, 1-hr time-weighted average exposures ranged from 0.5 to 45.5 ppm and 0.2 to 105.4 ppm, respectively.« less

Safety considerations of anesthetic drugs in children.

PubMed

Brown, Raeford E

2017-04-01

Great strides have been made in the last twenty years in providing safe anesthesia care for infants and children. Despite a historical record of safety, recent findings have called to question the toxicities of many anesthetic agents. Observations concerning the inherent safety of these agents, their appropriate management in infants, and new findings which suggest overlooked toxicities will be discussed. Areas covered: A literature search using Pub Med identified journal articles relating to the safety of anesthetic agents in infants and children. From this group, representative classical articles, as well as more recent offerings, were chosen that were germane to the topic of anesthetic drug safety in children. Expert opinion: Anesthetic agents used in children in the US are generally safe in the short term and are administered to thousands of children daily without demonstrable harm. The question of a deleterious effect of anesthetics on the developing central nervous system when used for long periods and on multiple occasions continues to be open to debate. Conservative elective management of these agents in infants and young children is reasonable until such time as more is known about the toxicities on the central nervous system.

Comparative Analysis of the Anesthetic Efficacy of 0.5 and 0.75 % Ropivacaine for Inferior Alveolar Nerve Block in Surgical Removal of Impacted Mandibular Third Molars.

PubMed

Bhargava, Darpan; Chakravorty, Nupur; Rethish, Elangovan; Deshpande, Ashwini

2014-12-01

Ropivacaine belongs to pipecoloxylidide group of local anesthetics. There are reports supporting the use of ropivacaine as a long acting local anesthetic in oral and maxillofacial surgical procedures, with variable data on the concentration that is clinically suitable. A prospective randomized double-blind study protocol was undertaken to assess the efficacy of 0.5 and 0.75 % ropivacaine for inferior alveolar nerve block in surgical extraction of impacted mandibular third molars. A total of 60 procedures were performed, of which thirty patients received 0.5 % and thirty received 0.75 % concentration of the study drug. All the patients in both the study groups reported subjective numbness of lip and tongue. The time of onset was longer for 0.5 % ropivacaine when compared to 0.75 % solution. 90 % of the study patients in 0.5 % ropivacaine group reported pain corresponding to VAS ≥3 during bone guttering and 93.3 % patients reported pain corresponding to VAS >4 during tooth elevation. None of the patients in 0.75 % ropivacaine group reported VAS >3 at any stage of the surgical procedure. The duration of soft tissue anesthesia recorded with 0.75 % ropivacaine was average 287.57 ± 42.0 min. 0.75 % ropivacaine was found suitable for inferior alveolar nerve blocks in surgical extraction of impacted mandibular third molars.

Altered states: psychedelics and anesthetics.

PubMed

Icaza, Eduardo E; Mashour, George A

2013-12-01

The psychedelic experience has been reported since antiquity, but there is relatively little known about the underlying neural mechanisms. A recent neuroimaging study on psilocybin revealed a pattern of decreased cerebral blood flow and functional disconnections that is surprisingly similar to that caused by various anesthetics. In this article, the authors review historical examples of psychedelic experiences induced by general anesthetics and then contrast the mechanisms by which these two drug classes generate altered states of consciousness.

Comparison of pain perception during miniscrew placement in orthodontic patients with a visual analog scale survey between compound topical and needle-injected anesthetics: A crossover, prospective, randomized clinical trial.

PubMed

Lamberton, Jordan A; Oesterle, Larry J; Shellhart, W Craig; Newman, Sheldon M; Harrell, Ricky E; Tilliss, Terri; Singh, Neha; Carey, Clifton M

2016-01-01

The use of a compound topical anesthetic (CTA) instead of an injection of a local anesthetic for placing miniscrew implants offers advantages to both the clinician and the patient. The purpose of this crossover, prospective, randomized clinical trial was to compare the clinical effectiveness of a CTA with that of a needle injection of local anesthetic for miniscrew placement. Twenty-four orthodontic patients in a university clinic were recruited; they required bilateral buccal miniscrews for orthodontic anchorage. Eligibility criteria included healthy patients with no special needs; over 8 years of age and 25 pounds; not taking sulfonamides, monoamine oxidase inhibitors, tricyclic antidepressants, or phenothiazines; and not allergic to ester-type local anesthetics or any of the other materials used in the study. A computer generated a randomization list. The allocation was randomized by anesthetic protocol and side of the mouth, and was restricted to achieve balance by treatment and side of the mouth. No allocation concealment was applied. Associated with each randomized number was the subjects' assignment into 1 of 4 groups divided by the side of first miniscrew placement and the type of anesthetic. Blinding was done only for data analysis because of clinical limitations. Each patient received a CTA on one side and an injection of anesthetic on the other before miniscrew placement in a crossover study design. The outcome was assessed by measuring pain levels with a 100-mm visual analog scale at 5 time points. Anesthetic failures occurred when the miniscrew could not be fully comfortably placed with a given anesthetic. Data were organized by visual analog scale time points, and descriptive statistics were calculated. A factorial repeated-measures analysis of variance was used to determine any differences. Twenty-seven patients were assessed for eligibility, and 24 agreed to participate in the study. Patients did not distinguish any differences in pain between the

An update on anesthetics and impact on the brain.

PubMed

Fodale, Vincenzo; Tripodi, Vincenzo F; Penna, Olivia; Famà, Fausto; Squadrito, Francesco; Mondello, Epifanio; David, Antonio

2017-09-01

While anesthetics are indispensable clinical tools and generally considered safe and effective, a growing concern over the potential neurotoxicity of anesthesia or specific anesthetic agents has called into question the safety of general anesthetics, especially when administered at extremes of age. Areas covered: This article reviews and updates research findings on the safety of anesthesia and anesthetics in terms of long-term neurotoxicity, with particular focus on postoperative cognitive dysfunctions, Alzheimer's disease and dementias, developing brain, post-operative depression and autism spectrum disorder. Expert opinion: Exposure to general anesthetics is potentially harmful to the human brain, and the consequent long-term cognitive deficits should be classified as an iatrogenic pathology, and considered a public health problem. The fact that in laboratory and clinical research only certain anesthetic agents and techniques, but not others, appear to be involved, raises the problem on what is the safest and the least safe anesthetic to maximize anesthesia efficiency, avoid occurrence of adverse events, and ensure patient safety. New trends in research are moving toward the theory that neuroinflammation could be the hallmark of, or could have a pivotal role in, several neurological disorders.

Effect of topical anesthetics on intraocular pressure and pachymetry.

PubMed

Montero, J A; Ruiz-Moreno, J M; Fernandez-Munoz, M; Rodriguez-Palacios, M I

2008-01-01

The determination of intraocular pressure (IOP) by noncontact tonometry (NCT) has been reported to be affected by central corneal thickness (CCT) and by the instillation of topical anesthetics. In order to determine the influence of topical anesthetics on CCT and IOP measured by NCT, 80 eyes from 49 patients were examined before and after the instillation of topical anesthetics. Average age was 55.3 years (SD 18.4, range 18 to 93). Twenty-eight patients were female and 21 were male. Average basal IOP was 16.1 mmHg (SD 5.2, range 8 to 35.3). IOP was 14.8 mmHg (SD 4.6, 7.4 to 32.4) (p=0.0005, Student t test for paired data) 5 minutes after topical anesthetics instillation. CCT averaged 541 micronm (SD 32, range 482 to 604) before topical anesthetic drops and 541 micronm (SD 32, 490 to 607, p=0.89, Student t test for paired data) 5 minutes after topical anesthetics instillation. The study confirms that the instillation of topical anesthetics causes a reduction in IOP. These changes do not seem to be associated with changes in CCT.

The evidence for reducing the pain of administration of local anesthesia and cosmetic injectables.

PubMed

Babamiri, Kajal; Nassab, Reza

2010-09-01

Administration of injections, whether local anesthetic or cosmetic injectable, can result in significant distress and discomfort to patients. This review explores factors that can alleviate anxiety and pain associated with injections including cosmetic injectables. We highlight that many techniques used to reduce pain have only been reported based on anecdotal evidence and small series. The techniques that have been reported to reduce pain, by randomized controlled trials, include pretreatment with topical local anesthetic agents and combined cosmetic injectables with local anesthetics. © 2010 Wiley Periodicals, Inc.

Can anesthetic treatment worsen outcome in status epilepticus?

PubMed

Sutter, Raoul; Kaplan, Peter W

2015-08-01

Status epilepticus refractory to first-line and second-line antiepileptic treatments challenges neurologists and intensivists as mortality increases with treatment refractoriness and seizure duration. International guidelines advocate anesthetic drugs, such as continuously administered high-dose midazolam, propofol, and barbiturates, for the induction of therapeutic coma in patients with treatment-refractory status epilepticus. The seizure-suppressing effect of anesthetic drugs is believed to be so strong that some experts recommend using them after benzodiazepines have failed. Although the rationale for the use of anesthetic drugs in patients with treatment-refractory status epilepticus seems clear, the recommendation of their use in treating status epilepticus is based on expert opinions rather than on strong evidence. Randomized trials in this context are lacking, and recent studies provide disturbing results, as the administration of anesthetics was associated with poor outcome independent of possible confounders. This calls for caution in the straightforward use of anesthetics in treating status epilepticus. However, there are still more questions than answers, and current evidence for the adverse effects of anesthetic drugs in patients with status epilepticus remains too limited to advocate a change of treatment algorithms. In this overview, the rationale and the conflicting clinical implications of anesthetic drugs in patients with treatment-refractory status epilepticus are discussed, and remaining questions are elaborated. This article is part of a Special Issue entitled "Status Epilepticus". Copyright © 2015 Elsevier Inc. All rights reserved.