Effect of preemptive use of a nonsteroidal anti-inflammatory drug and a corticosteroid on the efficacy of inferior alveolar nerve blockade and postoperative pain control in endodontic treatment of molars with symptomatic pulpitis: A randomized double-blind placebo-controlled clinical trial.

AIM: The anaesthetic success rate of an inferior alveolar nerve block (IANB) in mandibular molars with irreversible symptomatic pulpitis can be low, and postoperative pain control in teeth with this diagnosis can be challenging. This study aimed to evaluate the influence of preemptive use of dexamethasone and oral potassium diclofenac on the success of IANB. The influence of these drugs on the intensity of postoperative pain was assessed as a secondary outcome. METHODOLOGY: Eighty-four patients with mandibular molars diagnosed with irreversible symptomatic pulpitis recorded preoperative pain intensity using a cold thermal test and a modified Numerical Rating Scale (mNRS). Sixty minutes before the anaesthetic procedure, patients were randomly assigned to one of three groups based on the medication they received: dexamethasone (4 mg), diclofenac potassium (50 mg), or placebo. All patients received IANB with 4% articaine (1:200 000 epinephrine), and 15 min later, they were evaluated for pain intensity using the cold thermal test. Anaesthetic success was analysed. The pain intensity was then recorded, and endodontic treatment and provisional restoration of the tooth were executed in a single session. Patients were monitored for 6, 12, 24, 48 and 72 h using the mNRS to assess the intensity of postoperative pain. RESULTS: There was a statistically significant increase in anaesthetic success when 4 mg dexamethasone (39.3%) or 50 mg diclofenac potassium (21.4%) was used compared to the placebo group (3.6%) (p < .001), with no significant difference between the two drugs. Regarding postoperative pain, dexamethasone was superior to placebo at 6 h (p < .001), with diclofenac having an intermediate behaviour, not differing between dexamethasone and placebo (p > .05). There was no significant difference amongst the groups at 12 h (p > .05). At 24, 48 and 72 h, the effectiveness of dexamethasone and diclofenac were comparable, and both were superior to placebo (p < .001). CONCLUSION: The use of dexamethasone or diclofenac potassium was favourable in terms of increasing the success rate of inferior alveolar nerve block in cases of mandibular molars with irreversible symptomatic pulpitis and decreased the occurrence of postoperative pain when compared to the use of a placebo.

Antimicrobial and Anesthetic Niosomal Formulations Based on Amino Acid-Derived Surfactants.

BACKGROUND: This work proposes the development of new vesicular systems based on anesthetic compounds (lidocaine (LID) and capsaicin (CA)) and antimicrobial agents (amino acid-based surfactants from phenylalanine), with a focus on physicochemical characterization and the evaluation of antimicrobial and cytotoxic properties. METHOD: Phenylalanine surfactants were characterized via high-performance liquid chromatography (HPLC) and nuclear magnetic resonance (NMR). Different niosomal systems based on capsaicin, lidocaine, cationic phenylalanine surfactants, and dipalmitoyl phosphatidylcholine (DPPC) were characterized in terms of size, polydispersion index (PI), zeta potential, and encapsulation efficiency using dynamic light scattering (DLS), transmitted light microscopy (TEM), and small-angle X-ray scattering (SAXS). Furthermore, the interaction of the pure compounds used to prepare the niosomal formulations with DPPC monolayers was determined using a Langmuir balance. The antibacterial activity of the vesicular systems and their biocompatibility were evaluated, and molecular docking studies were carried out to obtain information about the mechanism by which these compounds interact with bacteria. RESULTS: The stability and reduced size of the analyzed niosomal formulations demonstrate their potential in pharmaceutical applications. The nanosystems exhibit promising antimicrobial activity, marking a significant advancement in pharmaceutical delivery systems with dual therapeutic properties. The biocompatibility of some formulations underscores their viability. CONCLUSIONS: The proposed niosomal formulations could constitute an important advance in the pharmaceutical field, offering delivery systems for combined therapies thanks to the pharmacological properties of the individual components.

Effects of Volatile Anesthetics versus Ketamine on Blood-Brain Barrier Permeability via Lipid-Mediated Alterations of Endothelial Cell Membranes.

The purpose of this study was to investigate the effects of the volatile anesthetic agents isoflurane and sevoflurane, at clinically relevant concentrations, on the fluidity of lipid membranes and permeability of the blood-brain barrier (BBB). We analyzed the in vitro effects of isoflurane or ketamine using erythrocyte ghosts (sodium fluorescein permeability), monolayers of brain microvascular endothelial cells ([13C]sucrose and fluorescein permeability), or liposomes (fluorescence anisotropy). Additionally, we determined the effects of 30-minute exposure of mice to isoflurane on the brain tight junction proteins. Finally, we investigated in vivo brain uptake of [13C]mannitol and [13C]sucrose after intravenous administration in mice under anesthesia with isoflurane, sevoflurane, or ketamine/xylazine in addition to the awake condition. Isoflurane at 1-mM and 5-mM concentrations increased fluorescein efflux from the erythrocyte ghosts in a concentration-dependent manner. Similarly, in endothelial cell monolayers exposed to 3% (v/v) isoflurane, permeability coefficients rose by about 25% for fluorescein and 40% for [13C]sucrose, whereas transendothelial resistance and cell viability remained unaffected. Although isoflurane caused a significant decrease in liposomes anisotropy values, ketamine/xylazine did not show any effects. Brain uptake clearance (apparent Kin) of the passive permeability markers in vivo in mice approximately doubled under isoflurane or sevoflurane anesthesia compared with either ketamine/xylazine anesthesia or the awake condition. In vivo exposure of mice to isoflurane did not change any of the brain tight junction proteins. Our data support membrane permeabilization rather than loosening of intercellular tight junctions as an underlying mechanism for increased permeability of the endothelial cell monolayers and the BBB in vivo. SIGNIFICANCE STATEMENT: The blood-brain barrier controls the entry of endogenous substances and xenobiotics from the circulation into the central nervous system. Volatile anesthetic agents like isoflurane alter the lipid structure of cell membranes, transiently facilitating the brain uptake of otherwise poorly permeable, hydrophilic small molecules. Clinical implications may arise when potentially neurotoxic drugs gain enhanced access to the central nervous system under inhalational anesthetics.

Evaluation of the sedative and physiological effects of intramuscular lidocaine in bearded dragons (Pogona vitticeps) sedated with alfaxalone.

OBJECTIVE: To evaluate if intramuscular (IM) lidocaine potentiates the sedative effects of alfaxalone and results in cardiopulmonary changes in sedated bearded dragons. STUDY DESIGN: Prospective experimental crossover study. ANIMALS: A group of eight adult bearded dragons (Pogona vitticeps) weighing 334 ± 46 g. METHODS: Animals were administered alfaxalone (10 mg kg-1 subcutaneously) and 15 minutes later either lidocaine 2% (4 mg kg-1) or 0.9% sodium chloride (0.2 mL kg-1) was administered IM in the thoracic limb. The treatments were randomized and separated by 7 days. Sedation was scored based on body position, eye closure, jaw tone, swallowing, pick up response, righting reflex and pelvic limb withdrawal reflex. Heart rate (HR) and respiratory rate (fR) were recorded every 5 minutes until recovery from sedation. RESULTS: Lidocaine had no significant effect on duration or depth of alfaxalone sedation. HR increased significantly for <10 minutes following lidocaine administration by a median (interquartile range) of 33% (28-37%; p = 0.024). No clinically significant effects on fR occurred following lidocaine injection. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of lidocaine 2% (4 mg kg-1) IM did not potentiate alfaxalone sedation but resulted in a transient clinically relevant increase in HR.

Monodisperse oligoethylene glycols modified Propofol prodrugs.

The low water solubility of Propofol resulted in complicated formulation and adverse effects during its clinical application. To improve its water solubility and maintain its anesthetic effects, Propofol prodrugs with monodisperse oligoethylene glycols as solubility enhancer were designed and synthesized. Monodisperse oligoethylene glycols enable the concise manipulation of water solubility, biocompatibility and anesthetic effects. Through the physicochemical and biological assay, a few water soluble prodrugs of Propofol were identified as promising anesthetic to overcome the drawbacks associated with Propofol.

Assessing anesthetic activity through modulation of the membrane dipole potential.

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 (F3), but not the structurally similar noninducer, 1,2-dichlorohexafluorocyclobutane (F6), 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.

Getting Hooked: A Simple Technique for the Treatment of Adhesive Injuries to the Eyelids.

BACKGROUND: Ocular chemical injuries due to accidental exposure or application of cyanoacrylate, commonly known as "superglue," have increased over the past 30 years. However, current treatment options to relieve eyelid adhesions due to cyanoacrylate applications are difficult to successfully execute and can require sedation or general anesthesia. Here we describe a simple technique to release eyelid adhesions due to cyanoacrylate, or other adhesive agents, that can be successfully performed at bedside without sedation. DISCUSSION: Topical anesthetic is instilled in the involved eye through an opening identified in the lid fissure. A Jameson muscle hook is inserted through the opening with the distal element of the hook normal to the surface of the eye. The hook is then pulled parallel to the lid margins and through the site of adhesion while counter pressure is applied with the fellow hand in the opposite motion of the hook. Residual glue from the eyelashes can be trimmed with blunt-tip scissors. Examination of the eyelids and ocular surface after application of the technique to open the eyelids showed successful release of adhesion sites with no additional injuries to the eye itself. CONCLUSIONS: A Jameson muscle hook can be used in emergency departments to safely and successfully relieve eyelid adhesions due to the inadvertent application of cyanoacrylate glue without the use of general anesthesia.

Comparison of patients with and without intellectual disability under general anesthesia: A retrospective study.

BACKGROUND AND PURPOSE: We analyzed and retrospectively compared patients with and without intellectual disability (ID) who underwent oral surgery under general anesthesia at Istanbul University, Faculty of Dentistry, Department of General Anesthesia, between October 2012 and June 2013 with regard to the following categories: Demographic features, American Society of Anesthesiologists (ASA) classification, Mallampati score, type of anesthetic drug used during the operation, type of intubation used, any difficulties with tracheal intubation, presence of systemic diseases, and recovery times after ending general anesthesia. MATERIALS AND METHODS: A total of 348 patients were selected from the Department of Maxillofacial Surgery and the Department of Pedodontics who underwent surgery with general anesthesia. Medical histories of all patients were taken, and their electrocardiography, chest X-rays, complete blood count, and blood clotting tests were checked during a preoperative assessment. Mallampati evaluations were also performed. Patients were grouped into ASA I, II, or III according to the ASA classification and were treated under general anesthesia. RESULTS: There was no significant difference between normal and intellectually disabled patients in terms of gender, Mallampati scores, intubation difficulties, mean anesthetic period, time to discharge, or postoperative nausea and vomiting. Epilepsy and genetic diseases in intellectually disabled patients were significantly more common than in non-ID (NID) patients. However, the frequency of diabetes and chronic obstructive pulmonary disease in NID patients was significantly higher than in the intellectually disabled patients. CONCLUSION: Dental treatment of intellectually disabled patients under general anesthesia can be performed just as safely as that with NID patients.

Neurosteroid Allopregnanolone Suppresses Median Nerve Injury-induced Mechanical Hypersensitivity and Glial Extracellular Signal-regulated Kinase Activation through γ-Aminobutyric Acid Type A Receptor Modulation in the Rat Cuneate Nucleus.

BACKGROUND: Mechanisms underlying neuropathic pain relief by the neurosteroid allopregnanolone remain uncertain. We investigated if allopregnanolone attenuates glial extracellular signal-regulated kinase (ERK) activation in the cuneate nucleus (CN) concomitant with neuropathic pain relief in median nerve chronic constriction injury (CCI) model rats. METHODS: We examined the time course and cellular localization of phosphorylated ERK (p-ERK) in CN after CCI. We subsequently employed microinjection of a mitogen-activated protein kinase kinase (ERK kinase) inhibitor, PD98059, to clarify the role of ERK phosphorylation in neuropathic pain development. Furthermore, we explored the effects of allopregnanolone (by mouth), intra-CN microinjection of γ-aminobutyric acid type A receptor antagonist (bicuculline) or γ-aminobutyric acid type B receptor antagonist (phaclofen) plus allopregnanolone, and allopregnanolone synthesis inhibitor (medroxyprogesterone; subcutaneous) on ERK activation and CCI-induced behavioral hypersensitivity. RESULTS: At 7 days post-CCI, p-ERK levels in ipsilateral CN were significantly increased and reached a peak. PD98059 microinjection into the CN 1 day after CCI dose-dependently attenuated injury-induced behavioral hypersensitivity (withdrawal threshold [mean ± SD], 7.4 ± 1.1, 8.7 ± 1.0, and 10.3 ± 0.8 g for 2.0, 2.5, and 3.0 mM PD98059, respectively, at 7 days post-CCI; n = 6 for each dose). Double immunofluorescence showed that p-ERK was localized to both astrocytes and microglia. Allopregnanolone significantly diminished CN p-ERK levels, glial activation, proinflammatory cytokines, and behavioral hypersensitivity after CCI. Bicuculline, but not phaclofen, blocked all effects of allopregnanolone. Medroxyprogesterone treatment reduced endogenous CN allopregnanolone and exacerbated nerve injury-induced neuropathic pain. CONCLUSIONS: Median nerve injury-induced CN glial ERK activation modulated the development of behavioral hypersensitivity. Allopregnanolone attenuated glial ERK activation and neuropathic pain via γ-aminobutyric acid type A receptors. Reduced endogenous CN allopregnanolone after medroxyprogesterone administration rendered rats more susceptible to CCI-induced neuropathy.

Inhibition of Nav1.7 channels by methyl eugenol as a mechanism underlying its antinociceptive and anesthetic actions.

AIM: Methyl eugenol is a major active component extracted from the Chinese herb Asari Radix et Rhizoma, which has been used to treat toothache and other pain. Previous in vivo studies have shown that methyl eugenol has anesthetic and antinociceptive effects. The aim of this study was to determine the possible mechanism underlying its effect on nervous system disorders. METHODS: The direct interaction of methyl eugenol with Na(+) channels was explored and characterized using electrophysiological recordings from Nav1.7-transfected CHO cells. RESULTS: In whole-cell patch clamp mode, methyl eugenol tonically inhibited peripheral nerve Nav1.7 currents in a concentration- and voltage-dependent manner, with an IC50 of 295 µmol/L at a -100 mV holding potential. Functionally, methyl eugenol preferentially bound to Nav1.7 channels in the inactivated and/or open state, with weaker binding to channels in the resting state. Thus, in the presence of methyl eugenol, Nav1.7 channels exhibited reduced availability for activation in a steady-state inactivation protocol, strong use-dependent inhibition, enhanced binding kinetics, and slow recovery from inactivation compared to untreated channels. An estimation of the affinity of methyl eugenol for the resting and inactivated states of the channel also demonstrated that methyl eugenol preferentially binds to inactivated channels, with a 6.4 times greater affinity compared to channels in the resting state. The failure of inactivated channels to completely recover to control levels at higher concentrations of methyl eugenol implies that the drug may drive more drug-bound, fast-inactivated channels into drug-bound, slow-inactivated channels. CONCLUSION: Methyl eugenol is a potential candidate as an effective local anesthetic and analgesic. The antinociceptive and anesthetic effects of methyl eugenol result from the inhibitory action of methyl eugenol on peripheral Na(+) channels.

A comparison of alfaxalone and propofol on intraocular pressure in healthy dogs.

OBJECTIVE: To compare the effects of alfaxalone and propofol on intraocular (IOP) pressure in the canine eye. ANIMALS STUDIED: Twenty-three healthy adult dogs. PROCEDURES: Dogs were randomized to receive intravenous propofol (n = 11) or alfaxalone (n = 12) until loss of jaw tone, 20 min after intravenous premedication (acepromazine 0.02-0.03 mg/kg and hydromorphone 0.05-0.1 mg/kg). IOP was measured at baseline (BL), 20 min postpremedication (postpremed), loss of jaw tone (postinduct), and immediately following orotracheal intubation (postintub). Between- and within-treatment effects were analyzed with two-way and one-way repeated measures ANOVA with Bonferroni's post hoc test, respectively. P < 0.05 was considered significant. RESULTS: No significant IOP differences were detected between alfaxalone or propofol groups at any time point (P > 0.05). Propofol: IOP did not change between BL (15.5 ± 2.7 mmHg) and postpremed (16.2 ± 3.6 mmHg, P > 0.05), or postinduct (19.1 ± 5.2 mmHg) and postintub (21.0 ± 4.6 mmHg, P > 0.05), but differed significantly between BL and postinduct (P < 0.0001), and postintub (P < 0.0001). Alfaxalone: IOP did not change between BL (15.7 ± 2.8 mmHg) and postpremed (15.3 ± 4.1 mmHg, P > 0.05), or postinduct (19.2 ± 4.9 mmHg) and postintub (20.5 ± 4.5 mmHg, P > 0.05), but differed significantly between BL and postinduct (P < 0.01), and postintub (P < 0.0001). CONCLUSIONS: These data show a potentially clinically significant increase in IOP following induction with propofol or alfaxalone, but no difference between agents.

Comparison of S(+)-ketamine and ketamine, with medetomidine, for field anaesthesia in the European brown hare (Lepus europaeus).

OBJECTIVE: To compare anaesthesia and recovery parameters of racemic ketamine or S(+)-ketamine in combination with medetomidine for intramuscular (IM) field anaesthesia in the European brown hare (EBH) (Lepus europaeus). STUDY DESIGN: Randomized, prospective, blinded clinical trial. ANIMALS: 20 adult EBH (eight male, 12 female), mean ± SD weight 3360 341). METHODS: Medetomidine (0.2 mg kg(-1) ) and ketamine (30 mg kg(-1) ) (K-M group) or S(+)-ketamine (15 mg kg(-1) ) (S-M group) were administered by IM injection. Time until first effect and loss of righting reflex were recorded. During sedation and anaesthesia heart rate, saturation of arterial haemoglobin, respiratory rate, side stream end tidal CO(2) (Pe'CO(2) ), non invasive blood pressure, body temperature, cardiorespiratory parameters, palpebral reflex, jaw tone and nociception were recorded every 5 minutes. Medetomidine was antagonized with IM atipamezole (1 mg kg(-1) ) 45 minutes after treatment injection. Time until first head lift, standing and total recovery time (T-Recov) were recorded. Incidences of falling and involuntary movements during recovery were counted. Recovery quality was scored by visual analogue scale. Descriptive statistics were used to visualize maintenance data. All other data were included in multiple linear regression models. RESULTS: Surgical anesthesia was not produced reliably with either protocol. Hypoxaemia occurred in both groups (SpO(2) < 90%). During recovery, falling was noted significantly less often (p < 0.001) in the S-M group (13 ± 7) versus the K-M group (27 ± 13). T-Recov was long, lasting for more than 3 hours in individuals with no significant differences between groups. CONCLUSION AND CLINICAL RELEVANCE: S(+)-ketamine showed only minor advantages over racemic ketamine. Surgical anaesthesia was not achieved reliably with either protocol. Oxygen supplementation should be considered to prevent hypoxaemia. Further research is needed to develop an injectable field protocol adequate for surgical procedures, but with a rapid smooth recovery.

Field anesthesia of wild ring-tailed lemurs (Lemur catta) using tiletamine-zolazepam, medetomidine, and butorphanol.

Telazol has been commonly used for field anesthesia of wild lemurs, including ring-tailed lemurs (Lemur catta). Telazol alone provides good induction, but doesn't cause adequate muscle relaxation and sedation for collecting consistent somatic measurements and high-quality dental impressions that are sometimes needed. Variability in induction response has been seen between individuals that have received similar dosages, with young lemurs seeming to need more anesthetic than mature lemurs. This investigation evaluated Telazol induction in young (2.0-4.9 yr) and mature (> or = 5.0 yr) ring-tailed lemurs and compared postinduction supplementation with medetomidine or medetomidine-butorphanol. Forty-eight lemurs were anesthetized with Telazol administered via blow dart; then, 20 min after darting, they were supplemented via hand injection with either medetomidine (0.04 mg/ kg) or medetomidine-butorphanol (0.04 mg/kg and 0.2 mg/kg, respectively). The odds ratio for young lemurs to need more than one dart for induction, relative to mature lemurs, was 3.8, even though the initial dose of Telazol received by young lemurs (19 +/- 7 mg/kg) was significantly higher than the initial dose administered to mature lemurs (12 +/- 5 mg/kg). The total Telazol dosage was also significantly different between young lemurs (33 +/- 15 mg/kg) and mature lemurs (18 +/- 9 mg/kg). Both medetomidine and medetomidine-butorphanol provided good muscle relaxation and sedation for all procedures. Physiologic values were similar between the two protocols. Oxygen saturation by pulse oximetry was generally good, although there were a few SaO2 values < 90%. Recoveries were smooth, but long. Time to head up was correlated with total Telazol dosage in mature lemurs. In young lemurs, time to standing was correlated with Telazol induction dosage and time of last Telazol administration. Lemurs that received hand injections of Telazol took longer to recover than those that did not. Further refinements are needed to increase induction reliability and to decrease recovery time, particularly in young lemurs.

A randomized cross-over trial assessing salivary and urinary cortisol concentrations after alfaxalone and propofol administration in healthy cats.

The aim of this study was to assess the effects of commonly used anaesthetics alfaxalone and propofol on salivary and urinary cortisol in healthy cats. Fifteen male castrated research-purposed cats received randomly intravenous continuous rate infusions of 8 mg/kg/h of alfaxalone, 12 mg/kg/h of propofol and 2 ml/kg/h of Lactated Ringer's solution for 30 min, with intervals of 6 days between treatments. Saliva samples were collected for 24 h before each infusion and for 24 h from the start of each infusion. Urine was collected as single pooled samples over each 24 h period. Mean integrated saliva cortisol responses in cats treated with alfaxalone were greater than responses of cats treated with propofol (P = 0.034) and controls (P = 0.017). Integrated responses in cats treated with propofol did not differ from controls. The mean urinary cortisol/creatinine ratio (UCCR) was higher on the day of treatment than the day before treatment in cats treated with alfaxalone (P < 0.0001) and in cats treated with propofol (P = 0.0168) and did not differ between days in cats treated with lactated Ringer's solution. The mean UCCR was higher in cats treated with alfaxalone than in cats treated with lactated Ringer's solution (P = 0.0020) on the day of treatment. Mean total urinary cortisol over 24 h was greater in cats treated with alfaxalone than controls (P = 0.0267). In conclusion, alfaxalone increased short-term salivary and urinary cortisol concentrations in healthy cats as compared to propofol and a control group of non-anesthetised cats.

Evaluation of isoeugenol for anesthesia in koi carp (Cyprinus carpio).

OBJECTIVE: To evaluate isoeugenol as an anesthetic agent in koi carp. ANIMALS: 216 juvenile koi carp (Cyprinus carpio). PROCEDURES: Fish were randomly allocated to 9 groups of 24, and each group was randomly exposed to isoeugenol concentrations ranging from 0 to 500 mg/L. General activity, excitement, fin and gill color changes, opercular movement rate, loss of equilibrium, muscle tone, jaw tone, and handleability were assessed. Five fish from the control (0 mg/L), 200 mg/L, and 500 mg/L groups were randomly selected prior to anesthetic recovery and again 24 hours after recovery for euthanasia, gross necropsy, and histologic assessment of gills, internal viscera, and skeletal muscles. RESULTS: Mean +/- SD interval to achieve stage 2 anesthesia with isoeugenol ranged from 22.4 +/- 6.2 minutes at 20 mg/L to 0.25 +/- 0.4 minutes at 500 mg/L, whereas the mean interval to stage 3 anesthesia ranged from 28.1 +/- 3.9 minutes at 20 mg/L to 0.33 +/- 0.48 minutes at 500 mg/L. With the exception of the 500 mg/L group, opercular movements were maintained throughout. Death was observed only in the 500 mg/L group, in which 50% of the fish either failed to recover or died within 24 hours after anesthetic exposure. There were no pathological differences between fish exposed to isoeugenol at 0 or 500 mg/L. CONCLUSIONS AND CLINICAL RELEVANCE: Isoeugenol appeared to have a wide margin of safety with predictable dose-related effects. Concentrations of 40 to 80 mg/L induced anesthesia within 4 to 11 minutes and were considerably less than the concentration associated with fish death.

[Perioperative management of epileptic patients].

The number of epileptic patients scheduled to receive anesthesia and operation is not small. The management of anesthesia for epileptic patients requires caution and prudence. It is necessary to continue their anticonvulsant therapy to avoid perioperative seizures. Anesthesiologists should consider the side effects of anticonvulsants such as liver dysfunction, renal dysfunction, anemia, and gingival hyperplasia. Drug interactions of anticonvulsants and muscle relaxants or opioids and other drugs are also to be considered. Volatile anesthetics and intravenous anesthetics have both anticonvulsant and convulsive properties, although the convulsive properties of clinical doses of these anesthetics are permissible.

Thermal behavior of a lipid-protein membrane model and the effects produced by anesthetics and neurotransmitters.

Despite decades of intense research to understand the phenomenon of anesthesia and its membrane-related changes in neural transmission, where lipids and proteins have been proposed as primary targets of anesthetics, the involved action mechanisms remain unclear. Based on the overall agreement that anesthetics and neurotransmitters induce particular modifications in the plasma membrane of neurons, triggering specific responses and changes in their energetic states, we present here a thermal study to investigate membrane effects in a lipid-protein model made of 1,2-dimyristoyl-sn-glycero-3-phosphocholine and albumin from chicken egg white under the influence of neurotransmitters and anesthetics. First, we observe how ovalbumin, ovotransferrin, and lysozyme (main albumin constituents from chicken egg white) interact with the lipid membrane enhancing their lipophilic character while exposing their hydrophobic domains. This produces a lipid separation and a more ordered hybrid lipid-protein assembly. Second, we measured the thermotropic changes of this assembly induced by acetylcholine, γ-aminobutiric acid, tetracaine, and pentobarbital. Although the protein in our study is not a receptor, our results are striking, for they give evidence of the great importance of non-specific interactions in the anesthesia mechanism.

The curse of discovery: pioneers of dental and medical anesthesia.

The current practice of dental local anesthesia remains founded upon drugs and techniques that were developed over 100 years ago. 2009 marks the 125th anniversary of the pioneering use of cocaine as a topical anesthetic and the introduction of nerve block injections in the oral cavity and facial region. Four famous clinicians are recognized in this article, each for their unique contributions to "modern" local anesthesia (Carl Köller, Sigmund Freud and William Halsted) and general anesthesia (Horace Wells), with the recognition of the adverse impact of drug dependence on their personal lives, which fortunately did not preclude their positively revolutionizing the practices of dentists and physicians and their patients every since.

Comparison of Isoflurane, Ketamine-Dexmedetomidine, and Ketamine-Xylazine for General Anesthesia during Oral Procedures in Rice Rats (Oryzomys palustris).

Rice rats (Oryzomys palustris) are an unconventional laboratory species that has been used to study photoperiodicity, periodontitis, and osteonecrosis of the jaw. Interventional procedures that require anesthesia, including oral procedures, are sometimes necessary in preclinical settings. The use of anesthetics including isoflurane and ketamine combined with α2-adrenoreceptor agonists, such as dexmedetomidine and xylazine, is well-established for laboratory rodents. However, their effects have been studied only modestly in rice rats. The aims of this study were to 1) determine the safety and consistency of 3 common anesthetic modalities in rice rats; 2) compare the physiologic and clinical responses to these anesthetics, and 3) verify the effectiveness of the most successful modality by testing it during an oral procedure (tooth extraction). Isoflurane, intraperitoneal ketamine-dexmedetomidine, and intraperitoneal ketamine-xylazine were evaluated by using a crossover design, in which each rat received all of the anesthetics. Compared with ketamine-dexmedetomidine and ketamine-xylazine, isoflurane inhalation through a nose cone produced more rapid induction, entry to a surgical plane of anesthesia, and initial recovery. In addition, isoflurane produced optimal anesthesia throughout the procedure for most rats. Unlike ketamine-dexmedetomidine and ketamine-xylazine, isoflurane did not alter rectal temperature, SpO2, or respiratory rate during the surgical tolerance period, whereas ketamine-dexmedetomidine and ketamine-xylazine decreased rectal temperature during the last stage of anesthesia and induced cardiorespiratory depression. Furthermore, 2 rats experienced negative outcomes warranting euthanasia: one after receiving ketamine-dexmedetomidine, and the other after ketamine-xylazine anesthesia. In conclusion, isoflurane was the most reliable and effective anesthetic in rice rats and maintained a surgical depth of anesthesia for as long as 30 min, thus supporting successful tooth extractions.

Anesthetic effects of dexmedetomidine-ketamine-midazolam administered intramuscularly in five-striped palm squirrels (Funambulus pennantii).

OBJECTIVE: To evaluate efficacy and safety of anesthesia with dexmedetomidine-ketamine-midazolam (DKM) in five-striped palm squirrels (Funambulus pennantii). ANIMALS: 8 male squirrels. PROCEDURES: Squirrels were anesthetized with DKM (dexmedetomidine, 0.1 mg/kg; ketamine hydrochloride, 30 mg/kg; and midazolam, 0.75 mg/kg) administered IM. Atipamezole (0.15 mg/kg) and flumazenil (0.1 mg/kg) were administered IM 40 minutes after induction of anesthesia. Vital signs and responses were recorded every 5 minutes during anesthesia. RESULTS: Anesthetic induction and recovery from anesthesia were rapid and without complications in all squirrels. Median anesthetic induction time was 67.5 seconds (interquartile [25th to 75th percentile] range, 5.5 seconds), and mean ± SD recovery time after drug reversal was 147 ± 79 seconds. Heart rate, respiratory rate, and rectal temperature significantly decreased during the anesthetic period. All squirrels became hypothermic by 40 minutes after induction. The righting reflex was absent during the 40-minute anesthetic period in all squirrels, with variable responses for the palpebral reflex, jaw tone, forelimb withdrawal reflex, and hind limb withdrawal reflex. Only 2 of 8 squirrels had loss of the limb withdrawal reflex in both the forelimbs and hind limbs from anesthetic induction to 25 minutes after induction. CONCLUSIONS AND CLINICAL RELEVANCE: DKM appeared to provide safe and effective anesthesia in five-striped palm squirrels, but oxygen and thermal support were indicated. At the doses administered, deep surgical anesthesia was not consistently achieved, and anesthetic depth of individual squirrels must be determined before surgical procedures are performed in palm squirrels anesthetized with this drug combination.