Low Anesthetic Concentrations Research Articles

The Continued Evolution of Peripartum Anesthesiologists

(Can J Anaesth. 2022;69:283–288. doi: 10.1007/s12630-021-02159-z) The role of an obstetric anesthesiologist has evolved from providing effective and safe analgesia and anesthesia during cesarean deliveries. Obstetric anesthesiologists now help ensure effective and safe neuraxial catheters; offer low concentrations of local anesthetics for epidural analgesia to minimize instrumental vaginal deliveries and maximize parturient movement; use vasopressors to reduce the risk of parturient hypotension; and develop emergency protocols to best treat adverse outcomes such as pre-eclampsia and hemorrhage.

Clinical Usefulness of the Anaesthetic Protocol Using Low Doses of Tiletamine – Zolazepam Combination in Continuous Rate Infusion as a Partial Intravenous Anaesthesia in Bitches Undergoing Laparoscopic Surgery

The objective of this study was to evaluate the clinical usefulness of the combination of tiletamine-zolazepam used in low doses as a continuous rate infusion in a partial intravenous anesthesia protocol. Fifteen clinically healthy, different breed bitches weighing 25.08 ± 10.39 kg was used in this study. After a food fast for at least 12 hours and water fast for 4 hours, the animals were premedicated with dexmedetomidine. After 15 minutes, the bolus of tiletamine-zolazepam combination was given as an. Induction of general anesthesia, immediately followed by continuous intravenous infusion. The following parameters were measured immediately after the induction of general anesthesia and lasted until the end of the surgery: electrocardiography, heart rate, systolic arterial blood pressure, diastolic arterial blood pressure, mean arterial blood pressure, body temperature respiratory rate end tidal of CO2. During the recovery period, pain level was evaluated as well as sedation assessment. Time for successful intubation after administration of the tiletamine-zolazepam combination was within 3 minutes. Heart rate was within reference values. Systolic, diastolic, and mean arterial blood pressure were also within the reference values. Internal body temperature showed a downward trend for a whole procedure time. During recovery, only 1 patient showed symptoms of pain and signs of dissociation. In summary, the partial intravenous protocol with the use of tiletamine-zolazepam combination and low anesthetic gases concentration is clinically useful because of ensuring the correct level of anesthesia and stability of intraoperative parameters as well as a good recovery period.

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.

The Unbearableness of Being Light.

The Unbearableness of Being Light.

Cellular stress and AMPK links metformin and diverse compounds with accelerated emergence from anesthesia and potential recovery from disorders of consciousness

The neural correlates of consciousness and the mechanisms by which general anesthesia (GA) modulate such correlates to induce loss of consciousness (LOC) has been described as one of the biggest mysteries of modern medicine. Several cellular targets and neural circuits have been identified that play a critical role in LOC induced by GA, including the GABAA receptor and ascending arousal nuclei located in the basal forebrain, hypothalamus, and brain stem. General anesthetics (GAs) including propofol and inhalational agents induce LOC in part by potentiating chloride influx through the GABAA receptor, leading to neural inhibition and LOC. Interestingly, nearly all GAs used clinically may also induce paradoxical excitation, a phenomenon in which GAs promote neuronal excitation at low doses before inducing unconsciousness. Additionally, emergence from GA, a passive process that occurs after anesthetic removal, is associated with lower anesthetic concentrations in the brain compared to doses associated with induction of GA. AMPK, an evolutionarily conserved kinase activated by cellular stress (e.g. increases in calcium [Ca2+] and/or reactive oxygen species [ROS], etc.) increases lifespan and healthspan in several model organisms. AMPK is located throughout the mammalian brain, including in neurons of the thalamus, hypothalamus, and striatum as well as in pyramidal neurons in the hippocampus and cortex. Increases in ROS and Ca2+ play critical roles in neuronal excitation and glutamate, the primary excitatory neurotransmitter in the human brain, activates AMPK in cortical neurons. Nearly every neurotransmitter released from ascending arousal circuits that promote wakefulness, arousal, and consciousness activates AMPK, including acetylcholine, histamine, orexin-A, dopamine, and norepinephrine. Several GAs that are commonly used to induce LOC in human patients also activate AMPK (e.g. propofol, sevoflurane, isoflurane, dexmedetomidine, ketamine, midazolam). Various compounds that accelerate emergence from anesthesia, thus mitigating problematic effects associated with delayed emergence such as delirium, also activate AMPK (e.g. nicotine, caffeine, forskolin, carbachol). GAs and neurotransmitters also act as preconditioning agents and the GABAA receptor inhibitor bicuculline, which reverses propofol anesthesia, also activates AMPK in cortical neurons. We propose the novel hypothesis that cellular stress-induced AMPK activation links wakefulness, arousal, and consciousness with paradoxical excitation and accelerated emergence from anesthesia. Because AMPK activators including metformin and nicotine promote proliferation and differentiation of neural stem cells located in the subventricular zone and the dentate gyrus, AMPK activation may also enhance brain repair and promote potential recovery from disorders of consciousness (i.e. minimally conscious state, vegetative state, coma).

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.

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

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.

Enhancement of α5-containing γ-aminobutyric acid type A receptors by the nonimmobilizer 1,2-dichlorohexafluorocyclobutane (F6) is abolished by the β3(N265M) mutation.

Modulation of γ-aminobutyric acid type A receptors (GABAARs) by general anesthetics may contribute to their ability to produce amnesia. Receptors containing α5 subunits, which mediate tonic and slow synaptic inhibition, are co-localized with β3 and γ2 subunits in dendritic layers of the hippocampus and are sensitive to low (amnestic) concentrations of anesthetics. Because α5 and β3 subunits influence performance in hippocampus-dependent learning tasks in the presence and absence of general anesthetics, and the experimental inhaled drug 1,2-dichlorohexafluorocyclobutane (F6) impairs hippocampus-dependent learning, we hypothesized that F6 would modulate receptors that incorporate α5 and β3 subunits. We hypothesized further that the β3(N265M) mutation, which controls receptor modulation by general anesthetics, would similarly influence modulation by F6. Using whole-cell electrophysiologic recording techniques, we tested the effects of F6 at concentrations ranging from 4 to 16 μM on receptors expressed in human embryonic kidney 293 cells. We measured drug modulation of wild-type α5β3 and α5β3γ2L GABAARs and receptors harboring the β3(N265M) mutation. We also tested the effects of F6 on α1β2γ2L receptors, which were reported previously to be insensitive to this drug when expressed in Xenopus oocytes. F6 enhanced the responses of wild-type α5β3γ2L but not α1β2γ2L receptors to low concentrations of GABA in a concentration-dependent manner. Receptors that incorporated the mutant β3(N265M) subunit were insensitive to F6. When applied together with a high concentration of GABA, F6 blocked currents through α5β3 but not α5β3γ2L receptors. F6 did not alter deactivation of α5β3γ2L receptors after brief high- concentration pulses of GABA. The nonimmobilizer F6 modulates GABAARs in a manner that depends on subunit composition and mode of receptor activation by GABA, supporting a possible role for α5-containing receptors in suppression of learning and memory by F6. Furthermore, common structural requirements indicate that similar molecular mechanisms may be responsible for the enhancing effects of F6 and conventional general anesthetics.

Cytotoxic Effects of Ropivacaine, Bupivacaine, and Lidocaine on Rotator Cuff Tenofibroblasts

Background: Concern has recently arisen over the safety of local anesthetics used on human tissues. Hypothesis: Aminoamide local anesthetics have cytotoxic effects on human rotator cuff tenofibroblasts. Study Design: Controlled laboratory study. Methods: Cultured human rotator cuff tenofibroblasts were divided into control, phosphate buffered saline (PBS), and local anesthetic study groups; the PBS study group was further subdivided by pH level (pH 7.4, 6.0, and 4.4). The 6 local anesthetic subgroups (0.2% and 0.75% ropivacaine, 0.25% and 0.5% bupivacaine, and 1% and 2% lidocaine) were also studied at 10% dilutions of their original concentrations. Exposure times were 5, 10, 20, 40, or 60 minutes for the higher concentrations and 2, 6, 12, 24, 48, or 72 hours for the lower concentrations. Cell viability was evaluated through live, apoptotic, and necrotic cell rates using the annexin V–propidium iodide double-staining method. Intracellular reactive oxygen species (ROS) and the activity of mitogen-activated protein kinases (MAPKs) and caspase-3/7 were investigated. Results: The control and PBS groups showed no significant differences in cell viability (P > .999). In the local anesthetic study groups, cell viability decreased significantly with increases in anesthetic concentrations (P < .001) and exposure times (P < .001), with the exception of the lidocaine subgroups, where this effect was masked by the very high cytotoxicity of even low concentrations. Among the studied local anesthetic subgroups, 0.2% ropivacaine was the least toxic. The levels of intracellular ROS of each local anesthetic subgroup also increased significantly (P < .05). The studied local anesthetics showed increases in the phosphorylation of extracellular signal–regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38 as well as in levels of caspase-3/7 activity (P < .001). Conclusion: The cytotoxicity of the anesthetics studied to tenofibroblasts is dependent on exposure time and concentration. Of the evaluated anesthetics, ropivacaine is the least toxic in the clinically used concentration. The studied anesthetics induce tenofibroblast cell death, mediated by the increased production of ROS, by the increased activation of ERK1/2, JNK, and p38 and by the activation of caspase-3/7. Clinical Relevance: This study identified the cytotoxic mechanisms of aminoamide local anesthetics acting on rotator cuff tenofibroblasts. The greatest margin of safety was found in lower anesthetic concentrations in general and more specifically in the use of ropivacaine.

The Effect of Low Concentrations Versus High Concentrations of Local Anesthetics for Labor Analgesia on Obstetric and Anesthetic Outcomes

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Postoperative Delirium in a Substudy of Cardiothoracic Surgical Patients in the BAG-RECALL Clinical Trial

Postoperative delirium in the intensive care unit (ICU) is a frequent complication after cardiac or thoracic surgery and is associated with increased morbidity and mortality. In this single-center substudy of the BAG-RECALL trial (NCT00682825), we screened patients after cardiac or thoracic surgery in the ICU twice daily for delirium using the Confusion Assessment Method for the ICU. The primary outcome was the incidence of delirium in patients who had been randomized to intraoperative Bispectral Index (BIS)-guided and end-tidal anesthetic concentration-guided depth of anesthesia protocols. As a secondary analysis, a Bayesian stochastic search variable selection strategy was used to rank a field of candidate risk factors for delirium, followed by binary logistic regression. Of 310 patients assessed, 28 of 149 (18.8%) in the BIS group and 45 of 161 (28.0%) in the end-tidal anesthetic concentration group developed postoperative delirium in the ICU (odds ratio 0.60, 95% confidence interval, 0.35-1.02, P= 0.058). Low average volatile anesthetic dose, intraoperative transfusion, ASA physical status, and European System for Cardiac Operative Risk Evaluation were identified as independent predictors of delirium. A larger randomized study should determine whether brain monitoring with BIS or an alternative method decreases delirium after cardiac or thoracic surgery. The association between low anesthetic concentration and delirium is a surprising finding and could reflect that patients with poor health are both more sensitive to the effects of volatile anesthetic drugs and are also more likely to develop postoperative delirium. Investigation of candidate methods to prevent delirium should be prioritized in view of the established association between postoperative delirium and adverse patient outcomes.

Influence of Body Mass Index and Epidural Anesthesia on Lung Function

I read with interest the report by Severgnini et al.1 in which they describe that the protective mechanical ventilation improves postoperative pulmonary function in patients undergoing open abdominal surgery with general anesthesia. However, we wish to raise two concerns which may undermine the clinical validity of the authors’ conclusions.First, the authors state that the exclusion criteria included patients with body mass index greater than 40 kg/m2. It means that the inclusion criteria included patients with body mass index 40 kg/m2 or less, and obese patients (mildly obese: body mass index 25–30; obese: body mass index >30) were also included in this study. Obesity is a risk factor for perioperative pulmonary complications as the pathophysiological changes induced by obesity may jeopardize respiratory function and contribute to pulmonary morbidity, such as hypoxemia, hypercapnia, and atelectasis.2 In addition, obesity is an important risk factor for perioperative impairment of spirometric measurements in patients undergoing laparotomy.3 There is a significant negative correlation between perioperative spirometric tests and obesity. The reduction in postoperative lung volumes was significantly greater in obese patients than in normal-weight patients. Also, surgery with general anesthesia may reduce lung volumes and this effect may be greater in the obese patients.4 So, we think the authors should give the information about the proportion of the obese patients in the two groups.Second, the authors state that most patients underwent epidural anesthesia at the T8 to T12 level before general anesthesia and received continuous analgesia after surgery. High thoracic perioperative epidural anesthesia was shown to decrease spirometric measurements by blocking intercostal muscle innervation.5 Even if low concentrations of local anesthetics are used, the sensory levels of epidural anesthesia extending from approximately T4 to L1 are likely to be accompanied by some degree of muscle paralysis.6 It is more likely to block the muscles of the abdominal wall (innervation T6–L1). Even a subtle decrease in abdominal muscle tone will affect dynamic parameters. To avoid the influence of the epidural anesthesia on spirometric measurements, we think it is necessary to perform a pulmonary functional test after the epidural anesthesia. Or else, the authors should give the information about the epidural anesthesia including the dose of the local anesthetics, the direction of the epidural catheter, and the plane of the epidural anesthesia.The authors declare no competing interests.

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.

Preconditioning Depolarizing Ramp Currents Enhance the Effect of Sodium Channel Blockers in Primary Sensory Afferents

The conformational state of voltage-gated sodium channels is an important determinant for the efficacy of both local anesthesia and electrical neuromodulation techniques. This study investigated the role of subthreshold preconditioning ramp currents on axonal nerve excitability parameters in the presence of sodium channel blockers in myelinated A and unmyelinated C fibers. A- and C-fiber compound action potentials were recorded extracellularly in vitro in saphenous nerve from adult rats. Nerve fibers were stimulated with a supramaximal current pulse either alone or after a 300-msec conditioning polarizing ramp current (between -10% and +100% of the original threshold current) in the presence and absence of lidocaine and tetrodotoxin (TTX). A computerized threshold tracking program (QTRAC), Institute of Neurology, University College London, London, UK) was used to determine the membrane thresholds. Preconditioning ramp currents of weak strengths increased membrane excitability. Stronger preconditioning ramp currents enhanced the potency of lidocaine and TTX to increase excitability thresholds. In A and C fibers stimulated with ramp currents of 110% (A fibers) and 40% (C fibers), lidocaine (80 μM) induced a 168 ± 15% (p < 0.001) and 302 ± 23% (p < 0.001) increase in threshold, respectively (no ramp current: 135 ± 9% and 124 ± 4%, respectively). TTX (16 nM) induced an increase in threshold of 455 ± 45% (p < 0.001) and 214 ± 22% (p = 0.005), respectively (no ramp current: 205 ± 12% and 128 ± 6%, respectively). Slow preconditioning ramp stimuli inactivate sodium currents. In the presence of sodium channel blockers, stronger ramp stimuli cause an increase in threshold, which is larger than that caused by the sodium channel blocker alone. Therefore, we conclude that small depolarizing ramp currents could be used to increase excitability threshold in the presence of low concentrations of local anesthetics. These additive effects might represent a target to address with peripheral nerve stimulation in order to suppress afferent pain signaling.

Sleeping Bubbles: Effects of Volatile Anesthetics in the Lateral Structure of Giant Unilamellar Vesicles

Volatile anesthetics have been widely used for more than 170 years. However, the mechanisms underlying the effects of anesthetics on membrane dynamics and structure are still under debate. Herein we study this problem for first time using fluorescence confocal microscopy experiments of giant Unilamellar Vesicles (GUVs). This approach allows obtaining spatially resolved information on membrane structure at a microscopic level.GUVs were prepared using DLPC/DPPC 3:7 mol. This mixture showed a characteristic gel (Lbeta)/liquid disordered (Lalfa) phase coexistence at room temperature, with line-shape domains (Lbeta) of variable width depending on the temperature[1]. The volatile anesthetic used was Sevoflurane. The administration strategies were two: high concentration with reduced exposure time; or low concentration (clinically relevant) with long term exposition.A dramatic alteration of the phase coexistence was observed, with a marked effect on the morphology of the gel phase domains. For the experiments with high anesthetic concentration, the boundaries of the domains became diffuse with an increment of the domain's perimeter/area ratio. When low anesthetic concentrations were used, a complete loss of the domains structure was observed with appearance of small circular shaped domains.Sevoflurane dramatically affected the lateral structure of the studied membranes, suggesting that similar mechanisms may occur in biological relevant membranes. Particularly, at low concentration of the anesthetic our results show some structural characteristic to that observed for cholesterol in canonical raft ternary lipid mixtures (formation of round domains). More research is underway to better understand the mechanisms underlying the sevoflurane effects on membranes.[1] L.A. Bagatolli and E. Gratton. 2000, Biophys J. 78:290-305.

Local Anesthetis and Adjuvants in Pediatric Regional Anesthesia

The pediatric loco-regional techniques are considered very safe and effective, first of all because they target the therapy directly to the site of surgery, decreasing the risks of intravenous analgesia. The quality of local anesthesia is influenced by structural and biophysical characteristics of local anesthetics drug, dose, site of injection, mixture of local anesthetics and possible addition of a vasoconstrictor or an adjuvant to prolong the analgesic effect. In children, unlike adults, small nerve diameters and short distance between Ranvier nodes permit to use large volumes and low concentrations of local anesthetics. The clinical practice has shown that in pediatric population, effective analgesia is obtained by 1% mepivacaine, 1% lidocaine and 0.25% bupivacaine or better 0.2% ropivacaine, 0.2-0.25% levobupivacaine. In addition, levobupivacaine and ropivacaine have a better profile in terms of safety in comparison to bupivacaine and are the local anesthetics of choice for the daily clinical practice also in children as in adults. Among the adjuvant, clonidine and ketamine showed the best pharmacokinetic and pharmacodynamic profiles of effective and safety, improving and prolonging the action of associated local anesthetics. Therefore, the use of enantiomers, in association with adjuvants as clonidine or ketamine, using the multimodal approach of integrated anesthesia, makes the clinical practice effective and safe in the pediatric operating rooms. This review focuses on the overview of local anesthetics and adjuvants used today in locoregional pediatric anesthesia, with an emphasis on the advantages and disadvantages of each drug.

Peripheral catheter techniques

With ultrasound, continuous peripheral nerve blocks (CPNBs) are one of the most recent developments in regional anesthesia in children. CPNBs are now used more widely in children because more suitable materials have been marketed, allowing complete, and prolonged postoperative pain control. Their use after orthopedic procedures in children and treatment for complex regional pain syndrome in adolescents has demonstrated the benefits. Perineural catheters have also shown their superiority over other techniques of continuous regional anesthesia in terms of side effects. The efficiency and the safety of these techniques may facilitate early ambulation with improved pain management, treatment at home with disposable pumps, and improved rehabilitation of children. Studies on large cohorts of patients published to date have failed to highlight any severe complications in their use compared with other adult studies. Accidents owing to systemic toxicity are very unlikely if the recommended maximum dose is not exceeded. The safety of continuous regional anesthesia techniques in children relies on the use of low-concentration l-enantiomer solutions (ropivacaine or levobupivacaine) accompanied by low plasma concentrations of local anesthetics, limiting the risk of systemic toxicity of these molecules. CPNB can ensure strong and lasting analgesia in hospital or at home.

Low Bispectral Index Values and Death

Low Bispectral Index Values and Death

Activation of TRPA1 by Membrane Permeable Local Anesthetics

BackgroundLow 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.ResultsRecombinant 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.ConclusionsThe 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.

Epidural analgesia for labor: Current techniques.

Epidural analgesia is an extremely effective and popular treatment for labor pain. In this review, we trace the history of the use of epidural analgesia and its refinements. We then outline the goals of treatment and methods used to attain those goals. The use of low concentrations of local anesthetics, combined with lipid-soluble opioids, does not impede the progress of labor or depress the newborn. The incidence of side effects is low. Maintenance of analgesia that allows patient control enhances patient satisfaction.