Higher Anesthetic Concentrations Research Articles

Exploring the effects of eugenol, menthol, and lidocaine as anesthetics on zebrafish glucose homeostasis

Zebrafish (Danio rerio) are widely employed as an experimental model in various scientific fields. The investigation of glucose metabolism dysfunctions has gained recent significant prominence. Considering that certain anesthetics may impact glycemic levels, it is imperative to carefully select an anesthetic that does not induce such side effects, thereby mitigating potential adverse influences on research outcomes. In this sense, this study aimed to evaluate potential glucose alterations and induction and recovery times resulting from the use of eugenol, menthol and lidocaine as anesthetics in zebrafish. A total of 150 adult male and female zebrafish were divided into ten groups, comprising a control group euthanized by rapid chilling, and three groups anesthetized with low (40 mg/L eugenol, 60 mg/L menthol, 100 mg/L lidocaine), intermediate (60 mg/L eugenol, 90 mg/L menthol, 225 mg/L lidocaine), and high (80 mg/L eugenol, 120 mg/L menthol, 350 mg/L lidocaine) anesthetic concentrations. Glucose levels and induction and recovery times were assessed. The findings reveal that eugenol and menthol did not cause glucose level alterations at any of the investigated concentrations, while lidocaine caused a non-concentration-dependent hyperglycemia. Eugenol and menthol also exhibited similar recovery times at different concentrations, while lidocaine recovery times were concentration-dependent. This study, therefore, concludes that eugenol and menthol are safe and satisfactory anesthetics for use in zebrafish research involving glucose analyses, while lidocaine use can cause biases due to altered glucose levels and safety concerns. Researchers should, therefore, carefully consider anesthetic selection to ensure reliable results in zebrafish assessments.

Development of NMDA receptors contributes to the enhancement of electroencephalogram oscillations under volatile anesthetics in rats.

Volatile anesthetics including sevoflurane and isoflurane enhance oscillations of cortical electroencephalogram (EEG), partly by their modulations on glutamate-mediated excitatory synaptic transmission. Expression of NMDA receptors is increased during neonatal development. However, how the development of NMDA receptors influences EEG under volatile anesthesia remains unclear. Expressions of NMDA receptor subtypes (NR1, NR2A, and NR2B) during neonatal development were measured by Western blotting. MAC (minimal alveolar concentration) of isoflurane and sevoflurane that inducing loss of righting reflex (LORR) and no response to tail-clamp (immobility) were measured to verify the effect of NR1 expression on anesthetic potency during neonatal development. Cortical electroencephalogram recording was used to examine the influence of NR1 expression on the power density of EEG. The expressions of GluNR1, GluNR2A and GluNR2B receptors were gradually increased during neonatal development in cortex, hippocampus and thalamus of rats. Knockdown of NR1 enhanced the sedative potency of volatile anesthetics but not on immobility potency in postnatal day 14 (P14)-P17 rats. For cortical EEG, along with the increased concentration of volatile anesthetics, cortical slow-delta oscillations of P5 rats were inhibited, theta and alpha oscillations were not changed significantly; while these oscillations were enhanced until high anesthetic concentrations in P21 rats. Knockdown of NR1 in forebrain suppressed the enhancement of cortical EEG oscillations in P21 rats. The development of NMDA receptors may contribute to the enhancement of cortical EEG oscillations under volatile anesthetics.

A Systematic Review and Meta-Analysis of Randomized Controlled Trials of Labor Epidural Analgesia Using Moderately High Concentrations of Plain Local Anesthetics versus Low Concentrations of Local Anesthetics with Opioids.

PurposeCompared to low concentrations of local anesthetics with opioids for labor epidural analgesia, very high concentrations of local anesthetics are associated with an increased risk of assisted vaginal delivery. We aimed to investigate if moderately high concentrations of plain local anesthetics are also associated with this risk.MethodsWe searched for published randomized controlled trials that compared moderately high concentrations of plain local anesthetics (>0.1% but ≤0.125% bupivacaine, >0.1% but ≤0.125% levobupivacaine, or >0.17% but ≤0.2% ropivacaine) to low concentrations of local anesthetics (≤0.1% bupivacaine, ≤0.1% levobupivacaine, or ≤0.17% ropivacaine) with opioids for labor analgesia. Meta-analyses were performed to compare the risk of assisted vaginal delivery and other perinatal outcomes between these two groups.ResultsWe identified nine randomized controlled trials with a total of 1334 participants. Meta-analysis of these nine trials showed no differences in the risks of assisted vaginal delivery (odds ratio [OR] = 1.18; 95% confidence interval [CI], 0.93–1.49) or Cesarean delivery (OR = 0.96; 95% CI, 0.71–1.29) between the two groups. The incidence of motor block was higher in the group of moderately high concentrations (OR = 4.05; 95% CI, 2.19–7.48), while the incidence of pruritus was lower (OR = 0.07; 95% CI, 0.03–0.16).ConclusionThis systematic review and meta-analysis suggests that the current evidence is inadequate to support that moderately high concentrations of plain local anesthetics increase the risk of assisted vaginal delivery compared to low concentrations of local anesthetics with opioids.

Short-Term Effects of 10% Lidocaine Ointment on Allodynia in Cancer Pain: A Randomized, Double-Blind, Placebo-Controlled Crossover Study.

Background: There is currently no established therapy for allodynia, which is a type of neuropathic pain. However, high concentrations of topical anesthetics can anesthetize the skin and increase the sensory threshold to tactile stimulation. Objective: We aimed to evaluate the short-term effects and safety of 10% lidocaine ointment for treating allodynia in cancer pain. Design: This was a randomized double-blind crossover study comparing the efficacies of 10% lidocaine ointment and placebo ointment for the treatment of static allodynia and spontaneous pain within 24 hours after ointment application, using a numerical rating scale (NRS). Setting/Subjects: The subjects were 25 cancer patients with current pain rating of ≥4 on NRS of static allodynia in cancer pain. Results: The NRS scores for static allodynia were significantly lower in the lidocaine group than in the placebo group at two to eight hours after initial ointment application. A total of 56% of patients (95% confidence interval 35%-77%) had NRS improvements of ≥50% at eight hours after lidocaine ointment application compared with 20% (3%-37%) after placebo ointment application. There was no interaction between time and group in terms of NRS values for spontaneous pain (p = 0.835), but a significant main effect of group was found, with NRS scores being significantly lower in the lidocaine group than in the placebo group (p = 0.027). There were no adverse events associated with lidocaine use. Conclusions: Lidocaine ointment 10% can alleviate allodynia for two to eight hours after application.

The diagnosis and management of shoulder pain.

Diagnosis is crucial in decision-making when treating a patient with shoulder pain. Ultrasound is also very important in the diagnostic and therapeutic pathway, especially when surgery is being considered. This article outlines the diagnostic pathway using the patient’s history, physical examination and ultrasound examination. It is important to correlate the clinical assessment with the imaging signs. It is also important to treat the patient and not the images as there may be abnormalities detected on imaging that are not symptomatic. The article covers the important diagnosis of subdeltoid subacromial bursitis, glenohumeral joint capsulitis, calcific tendinosis, acromioclavicular joint osteoarthritis and long head of biceps tendinosis. It will guide the reader in how to use the findings to treat, using ultrasound-guided injection and other techniques, including steroid injections, hydrodilatation, barbotage and extracorporeal shockwave treatment. These are discussed with the knowledge from over 30 years of experience with a literature review evidential support. I have included tips to make these procedures more effective in treatment and final outcome. There is discussion regarding the use of steroid injections in the presence of a rotator cuff tear and how to proceed if the patient has more than one disease process. The sensible use of steroids and local anesthetics are included, bearing in mind that lidocaine and high concentrations of long-acting local anesthetics are chondrotoxic and should not be injected into joints.

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

(Anesth Analg. 2017;124(5):1571–1580) Epidural analgesia may slightly prolong the second stage of labor and increase the instrumental birth rate, especially when high concentrations of local anesthetics are used. Consequently, low concentrations of local anesthetics (LCLAs) have become popular for epidural labor analgesia to help mediate second stage labor. The authors of the present study conducted a systematic review and meta-analysis to compare the effects of epidural analgesia with LCLAs with that of nonepidural analgesia on obstetric outcomes.

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

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.

Analgesic effect of perineural magnesium sulphate for sciatic nerve block for diabetic toe amputation: A randomized trial.

Background and objectivesHigh concentrations of local anesthetics may be neurotoxic for diabetic patients. Additive perineural administration of magnesium was reported to decrease the consumption of local anesthetics for nerve block. It was hypothesized that MgSO4 added to dilute ropivacaine was equianalgesic to more concentrated ropivacaine for toe amputations in diabetic patients.MethodsSeventy diabetic patients were allocated into 3 groups: 1) perineural 200 mg MgSO4 added to 0.25% ropivacaine, 2) 0.25% ropivacaine alone, and 3) 0.375% ropivacaine alone. All patients underwent popliteal sciatic nerve block that was guided by ultrasonography using the respective regimens. Time of onset, duration of motor and sensory block were recorded. Spontaneous and evoked pain score, worst pain score, additional analgesic consumption, satisfaction score and initial time of analgesic requirement of each patient were documented up to 48 hours postoperatively.ResultsIn comparison with 0.25% ropivacaine alone, magnesium supplement prolonged the duration of sensory block (p = 0.001), as well as better evoked pain score at 6 hour postoperatively (p = 0.001). In comparison with evoked pain score (1.6/10) in group of 0.375% ropivacaine, magnesium plus 0.25% ropivacaine presented a little higher score (2.5/10) at 6 hour postoperatively (p = 0.001), while lower worst pain score (p = 0.001) and less postoperative total analgesic consumption (p = 0.002).ConclusionsThe regimen of adding 200mg MgSO4 to 0.25% ropivacaine for sciatic nerve block yields equal analgesic effect in comparison with 0.375% ropivacaine. These findings have suggested that supplemental MgSO4 could not improve analgesic quality except reducing the total amount of local anesthetics requirement in diabetic toe amputations with sciatic nerve blocks.

A comparison of desflurane consumption according to fresh gas flow.

A comparison of desflurane consumption according to fresh gas flow.

The effect of low concentrations versus high concentrations of local anesthetics for labour analgesia on obstetric and anesthetic outcomes: a meta-analysis

The influence that different concentrations of labour epidural local anesthetic have on assisted vaginal delivery (AVD) and many obstetric outcomes and side effects is uncertain. The purpose of this meta-analysis was to determine whether local anesthetics utilized at low concentrations (LCs) during labour are associated with a decreased incidence of AVD when compared with high concentrations (HCs). We searched PubMed, Ovid EMBASE, Ovid MEDLINE, CINAHL, Scopus, clinicaltrials.gov, and Cochrane databases for randomized controlled trials of labouring patients that compared LCs (defined as ≤ 0.1% epidural bupivacaine or ≤ 0.17% ropivacaine) of epidural local anesthetic with HCs for maintenance of analgesia. The primary outcome was AVD and secondary outcomes included Cesarean delivery, duration of labour, analgesia, side effects (nausea and vomiting, motor block, hypotension, pruritus, and urinary retention), and neonatal outcomes. The odds ratios (OR) or weighted mean differences (WMD) and 95% confidence intervals (CI) were calculated using random effects modelling. An OR < 1 or a WMD < 0 favoured LCs. Eleven studies met our criteria (eight bupivacaine and three ropivacaine studies), providing 1,145 patients in the LCs group and 852 patients in the HCs group for analysis of the primary outcome. Low concentrations were associated with a reduction in the incidence of AVD (OR = 0.70; 95% CI 0.56 to 0.86; P < 0.001). There was no difference in the incidence of Cesarean delivery (OR 1.05; 95% CI 0.82 to 1.33; P = 0.7). The LCs group had less motor block (OR 3.9; 95% CI 1.59 to 9.55; P = 0.003), greater ambulation (OR 2.8; 95% CI 1.1 to 7.14; P = 0.03), less urinary retention (OR 0.42; 95% CI 0.23 to 0.73; P = 0.002), and a shorter second stage of labour (WMD -14.03; 95% CI -27.52 to -0.55; P = 0.04) compared with the HCs group. There were no differences between groups in pain scores, maternal nausea and vomiting, hypotension, fetal heart rate abnormalities, five-minute Apgar scores, and need for neonatal resuscitation. One-minute Apgar scores < 7 favoured the HCs group (OR 1.53; 95% CI 1.07 to 2.21; P = 0.02), and there was more pruritus in the LCs group (OR 3.36; 95% CI 1.00 to 11.31; P = 0.05). When compared with HCs of local anesthetics, the use of LCs for labour epidural analgesia reduces the incidence of AVD. This may be due to a reduction in the amount of local anesthetic used and the subsequent decrease in motor blockade. We therefore recommend the use of LCs of local anesthetics for epidural analgesia to optimize obstetric outcome.

Topical Anesthetics for Dermatologic Procedures: A Review

Practitioners are increasingly using topical anesthetics to decrease the pain associated with superficial dermatologic, aesthetic, and laser procedures. Numerous lidocaine-containing products are available, but comprehensive reviews are lacking regarding their relative safety profiles and appropriate dermatologic uses. A literature review of currently available topical anesthetics, their safety profiles, and dermatologic uses was conducted. Factors that should be considered to reduce the risk of side effects associated with the use of topical anesthetics include the amount of product used, body location, size of the surface area, and duration of product application. Many case reports document adverse outcomes associated with the use of compounded products that the Food and Drug Administration has not approved that have inappropriately high anesthetic concentrations and from the use of topical anesthetics on excessively large skin surface areas during laser treatments. Lidocaine-containing products play an integral role in cutaneous anesthesia by providing patient comfort with minimal side effects. Careful attention must be paid to the particular anatomic location, the total surface area covered, and the duration of anesthetic skin contact.

A Case of Horner's Syndrome following Ultrasound-Guided Infraclavicular Brachial Plexus Block

Horner's syndrome results from paralysis of the ipsilateral sympathetic cervical chain (stellate ganglion) caused by surgery, drugs (mainly high concentrations of local anesthetics), local compression (hematoma or tumor), or inadequate perioperative positioning of the patient. It occurs in 100% of the patients with an interscalene block of the brachial plexus and can also occur in patients with other types of supraclavicular blocks.In this case report, we presented a case of Horner's syndrome after performing an ultrasound-guided infraclavicular brachial plexus block with 15 mL of bupivacaine 0.5%. It appeared 40 minutes after the block with specific triad (ptosis, miosis, and exophtalmia) and quickly disappears within 2 hours and a half without any sequelae. Horner's syndrome may be described as an unpleasant side effect because it has no clinical consequences in itself. For this reason anesthesiologists should be aware of this syndrome, and if it occurs patients should be reassured and monitored closely.

Case Scenario: Anesthesia for Maternal-Fetal Surgery

Case Scenario: Anesthesia for Maternal-Fetal Surgery

Does Ultrasound-Guided Rectus Sheath Block Reduce Abdominal Pain in Patients with Postherpetic Neuralgia?

To the Editor Postherpetic neuralgia (PHN), one cause of severe neuropathic pain, is believed to result from both peripheral and central sensitization of herpes zoster.1 Clinically, antidepressants and anticonvulsants are recommended as the first line of treatment for PHN.2 However, the analgesic effect of these medications is limited,3 and nerve blocks, including epidural nerve block and root block, are used to reduce the pain and abnormal sensation such as allodynia associated with PHN. We recently treated a patient with PHN on the abdomen by ultrasound-guided rectus sheath block.4 We obtained the patient's written consent to report this case. A 71-year-old man reported 1 year of severe pain on the left side of the abdomen after herpes zoster (T-11 area). He had been treated with antidepressants and anticonvulsants without much success and was referred to our pain clinic. At the initial clinical visit, he complained of a burning, continuous pain on his left abdomen (T-8–T-11 area) with an intensity of 78 mm (out of 100) on a visual analog pain scale. His pain was limited between his anterior axillar line and the midline. The pain increased with movement and touching the area and was severe enough to interfere with his sleep. Mechanical allodynia was also present without any sensory loss at the painful area. After analyzing his clinical course and characteristics, the patient was diagnosed with PHN. Ultrasound-guided rectus sheath block was planned, and with the patient in the supine position, a 22-gauge, 70-mm short bevel nerve block needle (Plexufix®, B. Braun Melsungen AG, Melsungen, Germany) was inserted approximately 5 cm left lateral from his umbilicus under ultrasound guidance using a linear probe (MicroMaxx®, SonoSite Inc., Bothell, WA; HFL38 13 to 6 MHz linear probe), and 20 mL of 0.3% ropivacaine was injected to the periposterior rectus abdominis area. Ultrasonography showed local anesthetic spread between T-7 and T-12 segments. Fifteen minutes after the injection, the patient's spontaneous pain and mechanical allodynia disappeared completely. Analgesia was confirmed between T-8 and T-11 segments by pinprick. At the 1-month follow-up, the patient's pain had reduced to 25 mm on a visual analog pain scale, and mechanical allodynia had decreased. Therefore, an ultrasound-guided rectus sheath block was repeated 3 times at 14-day intervals, after which the pain and mechanical allodynia disappeared completely at the 3-month follow-up. No side effects were observed during the nerve block treatments. Ultrasound-guided rectus sheath block has several advantages in comparison with conventional nerve blocks including epidural nerve block. First, local anesthetics can be directly applied to peripheral nerves in the region of pain. Second, high concentrations of local anesthetics can be used. Third, the spread of applied local anesthetics can be confirmed by ultrasonography. Additional studies including proper controls are needed to confirm efficacy and safety of ultrasound-guided rectus sheath block in patients with abdominal pain due to PHN. Jitsu Kato, MD, PhD Kaname Ueda, MD Yuko Kondo, MD, PhD Mayu Aono, MD Dai Gokan, MD, PhD Miho Shimizu, MD, PhD Setsuro Ogawa, MD, PhD Department of Anesthesiology Nihon University Itabashi Hospital Tokyo, Japan [email protected]

Ultrasound Versus Landmark-Based Technique for Ilioinguinal-Iliohypogastric Nerve Blockade in Children: The Implications on Plasma Levels of Ropivacaine

Ilioinguinal-iliohypogastric nerve blockade (INB) is associated with high plasma concentrations of local anesthetics (LAs) in children. Ultrasonographic guidance enables exact anatomical administration of LA, which may alter plasma levels. Accordingly, we compared plasma levels of ropivacaine after ultrasonographic versus landmark-based INB. After induction of general anesthesia, 66 children (8-84 mo) scheduled for inguinal hernia repair received INB with 0.25 mL/kg of ropivacaine 0.5% (1.25 mg/kg) either by a landmark-based (n = 31) or by an ultrasound-guided technique (n = 35). Ropivacaine plasma levels were measured before (0) and 5, 10, 20, and 30 min after the LA injection, using high-performance liquid chromatography. Maximum plasma concentrations (C(max)), time to C(max) (t(max)), the absorption rate constant (k(a)), the speed of rise of the plasma concentration at Time 0 (dC(0)/dt), and area under the curve value (AUC) were determined. The ultrasound-guided technique resulted in higher C(max) (sd), k(a), dC(0)/dt, and AUC values and shorter t(max) compared with the landmark-based technique (C(max): 1.78 [0.62] vs 1.23 [0.70] microg/mL, P < 0.01; k(a): 14.4 [10.7] vs 11.7 [11.4] h(-1), P < 0.05; dC(0)/dt: 0.26 [0.12] vs 0.15 [0.03] microg/mL . min, P < 0.01; AUC: 42.4 [15.9] vs 27.2 [18.1] microg . 30 min/mL, P < 0.001; t(max): 20.4 [8.6] vs 25.3 [7.6] min, P < 0.05). The pharmacokinetic data indicate faster absorption and higher maximal plasma concentration of LA when ultrasound was used as a guidance technique for INB compared with the landmark-based technique. Thus, a reduction of the volume of LA should be considered when using an ultrasound-guided technique for INB.

Patient-Controlled Epidural Analgesia for Labor

Patient-controlled epidural analgesia (PCEA) for labor was introduced into clinical practice 20 yr ago. The PCEA technique has been shown to have significant benefits when compared with continuous epidural infusion. We conducted a systematic review using MEDLINE and EMBASE (1988-April 1, 2008) of all randomized, controlled trials in parturients who received PCEA in labor in which one of the following comparisons were made: background infusion versus none; ropivacaine versus bupivacaine; high versus low concentrations of local anesthetics; and new strategies versus standard strategies. The outcomes of interest were maternal analgesia, satisfaction, motor block, and the incidence of unscheduled clinician interventions. A continuous background infusion improved maternal analgesia and reduced unscheduled clinician interventions. Larger bolus doses (more than 5 mL) may provide better analgesia compared with small boluses. Low concentrations of bupivacaine or ropivacaine provide excellent analgesia without significant motor block. Many strategies with PCEA can provide effective labor analgesia. High volume, dilute local anesthetic solutions with a continuous background infusion appear to be the most successful strategy. Research into new delivery strategies, such as mandatory programmed intermittent boluses and computerized feedback dosing, is ongoing.

Concentration Effects of Volatile Anesthetics on the Properties of Model Membranes: A Coarse-Grain Approach

To gain insights into the molecular level mechanism of drug action at the membrane site, we have carried out extensive molecular dynamics simulations of a model membrane in the presence of a volatile anesthetic using a coarse-grain model. Six different anesthetic (halothane)/lipid (dimyristoylphosphatidylcholine) ratios have been investigated, going beyond the low doses typical of medical applications. The volatile anesthetics were introduced into a preassembled fully hydrated 512-molecule lipid bilayer and each of the molecular dynamics simulations were carried out at ambient conditions, using the NPT ensemble. The area per lipid increases monotonically with the halothane concentration and the lamellar spacing decreases, whereas the lipid bilayer thickness shows no appreciable differences and only a slight increase upon addition of halothane. The density profiles of the anesthetic molecules display a bimodal distribution along the membrane normal with maxima located close to the lipid-water interface region. We have studied how halothane molecules fluctuate between the two maxima of the bimodal distribution and we observed a different mechanism at low and high anesthetic concentrations. Through the investigation of the reorientational motions of the lipid tails, we found that the anesthetic molecules increase the segmental order of the lipids close to the membrane surface.

Anesthetic-induced Burst Suppression EEG Activity Requires Glutamate-mediated Excitatory Synaptic Transmission

Many anesthetics evoke electroencephalogram (EEG) burst suppression activity in humans and animals during anesthesia, and the mechanisms underlying this activity remain unclear. The present study used a rat neocortical brain slice EEG preparation to investigate excitatory synaptic mechanisms underlying anesthetic-induced burst suppression activity. Excitatory synaptic mechanisms associated with burst suppression activity were probed using glutamate receptor antagonists (CNQX and APV), GABA receptor antagonists, and simultaneous whole cell patch clamp and microelectrode EEG recordings. Clinically relevant concentrations of thiopental (50--70 microM), propofol (5--10 microM) or isoflurane (0.7--2.1 vol%, 0.5--1.5 rat minimum aveolar concentration (MAC), 200--700 microM) evoked delta slow wave activity and burst suppression EEG patterns similar to in vivo responses. These effects on EEG signals were blocked by glutamate receptor antagonists CNQX (8.6 microM) or APV (50 microM). Depolarizing intracellular bursts (amplitude=34.7+/-4.5 mV; half width=132+/-60 ms) always accompanied EEG bursts, and hyperpolarization increased intracellular burst amplitudes. Barrages of glutamate-mediated excitatory events initiated EEG bursting activity. Glutamate-mediated excitatory postsynaptic currents were significantly depressed by higher anesthetic concentrations that depressed burst suppression EEG activity. A GABA(A) agonist produced a similar EEG effect to the anesthetics. It appears that anesthetic effects at both glutamate and GABA synapses contribute to EEG patterns seen during anesthesia.

Questioning the Mechanism of Nerve Injury

We were struck by the title “Possible Mechanism of Irreversible Nerve Injury Caused by Local Anesthetics” that appeared recently in Anesthesiology.1Kitagawa et al. 1showed that “local anesthetics used clinically can form molecular aggregations at high concentrations, resulting in the appearance of detergent properties in these agents.” They concluded, “The mechanisms of irreversible neurologic injury induced by high concentrated local anesthetic seem likely to result from the detergent nature of local anesthetics.”In 1994, we published results of in vitro experiments regarding the irreversible conduction block associated with high concentrations of local anesthetics.2In that publication, we examined the changes in the compound resting potential (CRP) of the isolated frog sciatic nerve. The CRP, like the compound action potential (CAP), is an average of membrane potentials of all the fibers in the nerve bundle. The CRP became less negative (by 18 ± 2 mV, n = 3) when 5% lidocaine was placed in the drug exposure pool. The kinetics of this apparent depolarization consisted of a rapid phase of 5–10 mV in amplitude, occurring in less than 10 s, and a slow phase of 10–15 mV amplitude, taking 10–15 min to reach steady state. The CAP amplitude decreased to zero within 40 s of exposure to 5% lidocaine. On replacement of lidocaine by amphibian Ringer’s solution, this apparent depolarization reversed with a corresponding rapid and slow phase, and the CRP was restored to within 2–4 mV of its predrug value after a 2-h washout, although the CAP did not reappear. A similar depolarization of 24 ± 4 mV, consisting of rapid and slow phases, resulted when the nerve was exposed to 200 mm choline chloride dissolved in Ringer’s solution. In the choline chloride Ringer’s solution, however, the action potential amplitude only decreased by 58.8 ± 6.4% (n = 4) and recovered to within 3.2 ± 0.8% of the initial value after a 50-min wash in Ringer’s solution. It is likely that the rapid apparent depolarization is actually an ionic solution artifact resulting from the interaction of the silver–silver chloride electrode in the test pool with the increased [Cl−] present in both 5% (185 mm) lidocaine hydrochloride and 200 mm choline chloride. The mechanism of the slow phase is unclear, but both phases of this depolarization seem to result from differences in the ionic composition and not tonicity, because exposure of two nerves to Ringer’s solution containing 400 mm dextrose (7.2%, equally hypertonic to the lidocaine) changed the CRP by less than 0.4 mV, accompanied by small reductions of the CAP (11% and 18%) that remained after 2 h of washing in Ringer’s solution. In contrast, if the nerve was intentionally lysed by 5% sodium lauryl sulfate (an ionic detergent) in Ringer’s solution, the CRP disappeared within 3 min (a permanent depolarization of 30–40 mV),3accompanied by an irretrievable loss of the action potential.At first glance, the mechanism proposed by Kitagawa et al. seems plausible. However, our data suggest that lysis of the nerve cell membrane resulting from a detergent action is not the mechanism for irreversible nerve injury that we observed in an isolated nerve preparation. It seems more likely that the local anesthetic injury that we observed resulted from a “wrecking” of the sodium conductance system (lack of CAP generation) in the face of preserved membrane structure, ionic gradients, and CRP.* Boston University Medical School, Boston Medical Center, Boston, Massachusetts. donald.lambert@bmc.org

Pharmacologic and physiologic influences affecting sensory evoked potentials: implications for perioperative monitoring.

Pharmacologic and physiologic influences affecting sensory evoked potentials: implications for perioperative monitoring.