Molecular Diversity of Anesthetic Actions Is Evident in Electroencephalogram Effects in Humans and Animals.

Anesthetic agents cause unique electroencephalogram (EEG) activity resulting from actions on their diverse molecular targets. Typically to produce balanced anesthesia in the clinical setting, several anesthetic and adjuvant agents are combined. This creates challenges for the clinical use of intraoperative EEG monitoring, because computational approaches are mostly limited to spectral analyses and different agents and combinations produce different EEG responses. Thus, testing of many combinations of agents is needed to generate accurate, protocol independent analyses. Additionally, most studies to develop new computational approaches take place in young, healthy adults and electrophysiological responses to anesthetics vary widely at the extremes of age, due to physiological brain differences. Below, we discuss the challenges associated with EEG biomarker identification for anesthetic depth based on the diversity of molecular targets. We suggest that by focusing on the generalized effects of anesthetic agents on network activity, we can create paths for improved universal analyses.

Retrospective Comparison between the Effects of Propofol and Inhalation Anesthetics on Postoperative Recurrence of Early- and Intermediate-Stage Hepatocellular Carcinoma.

OBJECTIVE: Previous studies have reported that propofol has antitumor, anti-inflammatory, and antioxidant effects in addition to its anesthetic properties. To confirm this, a retrospective investigation was conducted to determine whether different anesthetic agents, particularly propofol and inhalation anesthetics, have an effect on the recurrence of hepatocellular carcinoma (HCC) in patients who were diagnosed with primary HCC and underwent laparoscopic hepatectomy. SUBJECTS AND METHODS: Patients with Barcelona Clinic Liver Cancer stages 0, A, and B HCC, who underwent laparoscopic hepatic resection, were enrolled in this study. Post-operative HCC recurrence, which was determined from postoperative liver CT, was evaluated 24 months postoperatively with respect to the main anesthetic agents. The characteristics of HCC and other patient-related or surgery-related variables were evaluated together. RESULTS AND CONCLUSION: During the 24-month period after hepatic resection, less HCC patients in the propofol group than in the inhalation group recurred (p = 0.046). The mean time to recurrence was 20.8 months (95% CI, 19.7-22.0) and 19.1 months (95% CI, 17.8-20.4) in the propofol group and the inhalation group, respectively. In addition, multivariable Cox proportional regression analysis revealed that the propofol group showed significantly decreased recurrence versus the inhalation group (hazard ratio, 0.57; 95% CI, 0.47-0.69; p = 0.029). When propofol was used as the main general anesthetic agent for laparoscopic hepatic resection, the postoperative 2-year recurrence rate decreased in early- and intermediate-stage HCC.

Parenterally administered moderate sedation and paracervical block versus general anesthesia for hysteroscopic polypectomy: a pilot study comparing postoperative outcomes.

STUDY OBJECTIVE: To compare parenterally administered moderate sedation and paracervical block versus general anesthesia during day-case operative hysteroscopy for polypectomy in terms of patients' postoperative pain perception, operating time, and postoperative drug administration. DESIGN: A pilot study (Canadian Task Force classification I). SETTING: A university hospital. PATIENTS: Women undergoing hysteroscopic polypectomy procedures (N = 56). INTERVENTIONS: Hysteroscopic polypectomy with general anesthesia or moderate parenteral sedation and paracervical block. MEASUREMENTS AND MAIN RESULTS: The patients were divided into 2 groups: 26 underwent general anesthesia (group 1), and 30 were submitted to moderate parenteral sedation and a paracervical block (group 2). General anesthesia was induced with the laryngeal mask airway with propofol (1% 1-2.5 mg/kg) and fentanyl (1-2 µg/kg) and maintained with an infusion of propofol (2% 3-5 mg/kg/h). After the procedure, patients in the general anesthesia group received postoperative analgesic medication with paracetamol (20 mg/kg) and ketorolac (0.6 mg/kg) or tramadol (2-3 mg/kg). The group receiving moderate parenterally sedation and a paracervical block received a paracervical block with mepivacaine (1% 10 mL) and lidocaine (2% 10 mL) and received fentanyl (1 µg/kg) and propofol (1% 1-3 mg/kg/h) maintaining spontaneous breathing. A blind observer recorded the operative time and the discomfort of patients using a 4-step scale (0-3). The postoperative pain assessment was performed 3 hours after the procedure with a self-administered validated tool, the Brief Pain Inventory. We found that women receiving moderate parenteral sedation and a paracervical block perceived significantly less pain in daily activity (p < .001), walking (p < .001), daily work (p < .001), relations with others (p = .007), sleep (p < .001), and pain contrasting enjoyment of life (p < .001). The total amount of time spent in the operating room in group 2 was significantly lower than in group 1 (p < .014). CONCLUSION: Moderate sedation plus a paracervical block for operative hysteroscopy is associated with reduced pain perception and a shorter operative time.

Undiagnosed myopathy before surgery and safe anaesthesia table.

Patients with muscle pathology are a challenge for anaesthesiologists because of possible life-threatening general anaesthesia complications. A review of the current medical literature on the issue clearly indicates that increasing awareness by anaesthesiologists in recent years has led to a reduction in the occurrence of adverse events in patients with diagnostically well-defined muscle disease. On the other hand, the current emerging aspect is that the great majority of complications concern subjects with clinically non-overt (silent to mildly symptomatic) and thus undiagnosed myopathy. With a view to improving prevention of possible critical anaesthesia complications in such patients, we present a "Safe Anaesthesia Table", listing both the anaesthetic drugs to be avoided and those considered harmless for myopathic patients, irrespective of age and type of pathology. In addition, a brief outline about the clinical aspects suggestive of a possible muscle pathology is also provided. Using "safe drugs" during routine surgical procedures in subjects with suspected undiagnosed myopathy will enable the anaesthesiologist to avoid delaying surgery, while protecting them from anaesthesia complications. By following this approach the presumed myopathy can be properly investigated after surgery.

Choice of Perioperative Anesthetic Medications in Patients Undergoing Bariatric Surgery.

The prevalence of obesity is increasing globally. Rational perioperative anesthetic drug selection and administration require knowledge of how obesity interacts with those drugs. In this review, we summarize different aspects of the anesthetic agents, including pharmacokinetics (PK), pharmacodynamics (PD) and clinical application of the most commonly used medications with particular focus on the enhanced recovery of the obese patient.

Opioid Free Anaesthesia and Cancer.

Opioid-free anesthesia is revolutionizing anesthetic practices for its potential benefits in selected patients. Opioid-free anesthesia represents a step forward in anesthetic practice as it has been suggested to provide potential clinical benefits for selected patients. Opioid-free anesthesia spares the use of opioids and involves the administration of multiple adjuvant anesthetics, which may have an impact on cancer progression. All this have added to the growing interest in the immune response to anesthetics, making opioid-free anesthesia a promising avenue for future research. Assessing the role of anesthetics in immunomodulation in the surgical setting is challenging, and results are often contradictory. Indeed, there is a scarcity of data of studies on humans, which hinder the interpretation of results. However, promising evidence has been published that cancer progression can be delayed by the administration of specific anesthetic agents.

Top 60 medications used for orofacial pain treatment.

This article introduces the 60 top pharmacologic treatments provided for chronic orofacial pain patients. It explains that the majority of "chronic" orofacial pain patients will not find a "cure" to their pain with medications but may find a way to manage their pain. The medications in this article are the most commonly utilized "pain" medications and where it exists. This article reviews some of the current evidence supporting their use on chronic orofacial pain disorders.

Prevalencia del uso de anestésicos subcutáneos para la realización de gasometrías arteriales en el servicio de urgencias / Prevalence of use of subcutaneous anesthesics for performing arterial blood gas sample in emergency department

Objetivo: Determinar el porcentaje de enfermeras que, siguiendo las normativas actuales de la SEPAR, administran un anestésico subcutáneo previo a la realización de una gasometría arterial en el servicio de urgencias.Método: Se realizó un estudio observacional descriptivo en el servicio de urgencias del Hospital Clínico de Barcelona, mediante un cuestionario de 11 preguntas. En el estudio podrían participar todos los trabajadores de enfermería que hubiesen realizado al menos una extracción de gasometría arterial en el último año.Resultados: 82 respuestas fueron aceptadas para el estudio. 64 mujeres y 28 hombres, un 45,12% de ellos llevaban en el servicio 5 años o menos. Sólo un 15,8% utilizaban de forma habitual algún tipo de anestésico, siendo el espray de cloruro de etilo el método más utilizado, mientras que la mepivacaina subcutánea era el método menos común. Por el contrario, un 84,2% no utilizaban ningún método anestésico para la realización de dicha prueba, siendo el estado de urgencia del paciente el motivo más habitual para justificarlo.Conclusiones: El uso de anestésicos subcutáneos está muy poco extendido en la práctica diaria debido a falta de una formación adecuada y a la presión asistencial. Todo esto, unido al hecho de que el dolor percibido por el paciente está relacionado con la rapidez y la facilidad para realizar la técnica, se pone en evidencia la necesidad de buscar un método rápido y eficaz para el control del dolor en la realización de gasometrías en el servicio de urgencias. (AU)

Objective: To determine the percentage of nurses who, following SEPAR regulations, administer a subcutaneous anesthetic prior to performing an arterial blood gas test in the emergency department.Method: A descriptive observational study was carried out in the emergency department of the Barcelona Clinic Hospital, using an eleven questions survey. All nursing workers who had performed at least one arterial blood gas extraction over the last year could take part in the study.Results: 82 responses were accepted. 64 women and 28 men, 45.12% of them had been in the service for 5 years or less. Only 15.8% extensively used some type of anesthetic, ethyl chloride spray was the most widely used method, while subcutaneous mepivacaine was the least. On the other hand, 84.2% did not use any anesthetic method to perform this test and the patient’s state of emergency was the main reason to justify it.Conclusions: The use of subcutaneous anesthetics is not usual in everyday practice due to the lack of knowledge and the assistance pressure. All this, together with the fact that the pain perceived by the patient is related to the duration and ease to perform the technique, highlights the need to look for a quick and effective method for blood gas puncture pain management at the emergency department. (AU)

Development of monolithic matrix type transdermal patches containing cinnarizine: Physical characterization and permeation studies

To overcome the problems associated with bioavailability and systemic side effects of the drug by oral administration, monolithic matrix type transdermal patches containing cinnarizine (CNZ) were developed. For this purpose, films based on hydroxypropyl methylcellulose and polyvinylpyrrolidone as matrix-forming polymers were designed. Physical characteristics of transdermal films and drug-excipient compatibility were investigated. Factors affecting in vitro drug release and ex vivo skin penetration and permeation of the drug were studied. It was confirmed that films displayed sufficient flexibility and mechanical strength for application onto the skin for a long time period. Ex vivo penetration experiments gave satisfactory results for transdermal drug delivery through rat skin. The parameters determining good skin penetration were also evaluated. The highest drug permeation rate was obtained with incorporation of Transcutol® (0.102 mg/cm2/h) into the base CNZ formulation, followed by propylene glycol (0.063 mg/cm2/h), menthol (0.045 mg/cm2/h), and glycerin (0.021 mg/cm2/h) as penetration enhancers (p < 0.05). As a result, the developed transdermal patches of CNZ may introduce an alternative treatment for various conditions and diseases such as idiopathic urticarial vasculitis, Ménière's disease, motion sickness, nausea, and vertigo. Thus, the risk of systemic side effects caused by the drug can be reduced or eliminated

Impact of Stroke Therapy Academic Industry Roundtable (STAIR) Guidelines on Peri-Anesthesia Care for Rat Models of Stroke: A Meta-Analysis Comparing the Years 2005 and 2015.

Numerous studies using rats in stroke models have failed to translate into successful clinical trials in humans. The Stroke Therapy Academic Industry Roundtable (STAIR) has produced guidelines on the rodent stroke model for preclinical trials in order to promote the successful translation of animal to human studies. These guidelines also underline the importance of anaesthetic and monitoring techniques. The aim of this literature review is to document whether anaesthesia protocols (i.e., choice of agents, mode of ventilation, physiological support and monitoring) have been amended since the publication of the STAIR guidelines in 2009. A number of articles describing the use of a stroke model in adult rats from the years 2005 and 2015 were randomly selected from the PubMed database and analysed for the following parameters: country where the study was performed, strain of rats used, technique of stroke induction, anaesthetic agent for induction and maintenance, mode of intubation and ventilation, monitoring techniques, control of body temperature, vascular accesses, and administration of intravenous fluids and analgesics. For each parameter (stroke, induction, maintenance, monitoring), exact chi-square tests were used to determine whether or not proportions were significantly different across year and p values were corrected for multiple comparisons. An exact p-test was used for each parameter to compare the frequency distribution of each value followed by a Bonferroni test. The level of significant set at < 0.05. Results show that there were very few differences in the anaesthetic and monitoring techniques used between 2005 and 2015. In 2015, significantly more studies were performed in China and significantly fewer studies used isoflurane and nitrous oxide. The most striking finding is that the vast majority of all the studies from both 2005 and 2015 did not report the use of ventilation; measurement of blood gases, end-tidal carbon dioxide concentration, or blood pressure; or administration of intravenous fluids or analgesics. The review of articles published in 2015 showed that the STAIR guidelines appear to have had no effect on the anaesthetic and monitoring techniques in rats undergoing experimental stroke induction, despite the publication of said guidelines in 2009.

Recipes for obstetric spinal hypotension: The clinical context counts.

Hypotension following obstetric spinal anaesthesia remains a common and important problem. While recent research advances have brought us closer to the perfect recipe for the obstetric spinal anaesthetic, these advances have not been translated into practical guidelines able to reduce the unacceptable number of fatalities that occur in environments where resources are limited. In South Africa, more than half of anaesthetic deaths are still related to spinal hypotension. A gap exists between the 'perfect recipe', developed from a clinical context rooted in resource-rich research environments, and its application and performance in real-world resource-poor environments - conditions experienced by more than 75% of the world's population. This review attempts to define this knowledge gap and proposes a research agenda to address the deficiencies.

General anesthesia in cardiac surgery: a review of drugs and practices.

General anesthesia is defined as complete anesthesia affecting the entire body with loss of consciousness, analgesia, amnesia, and muscle relaxation. There is a wide spectrum of agents able to partially or completely induce general anesthesia. Presently, there is not a single universally accepted technique for anesthetic management during cardiac surgery. Instead, the drugs and combinations of drugs used are derived from the pathophysiologic state of the patient and individual preference and experience of the anesthesiologist. According to the definition of general anesthesia, current practices consist of four main components: hypnosis, analgesia, amnesia, and muscle relaxation. Although many of the agents highlighted in this review are capable of producing more than one of these effects, it is logical that drugs producing these effects are given in combination to achieve the most beneficial effect. This review features a discussion of currently used anesthetic drugs and clinical practices of general anesthesia during cardiac surgery. The information in this particular review is derived from textbooks, current literature, and personal experience, and is designed as a general overview of anesthesia during cardiac surgery.

Genotoxicity of Anesthetics Evaluated In Vivo (Animals).

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

International online survey to assess current practice in equine anaesthesia.

REASONS FOR PERFORMING STUDY: Multicentre Confidential Enquiries into Perioperative Equine Fatalities (CEPEF) have not been conducted since the initial CEPEF Phases 1-3, 20 years ago. OBJECTIVES: To collect data on current practice in equine anaesthesia and to recruit participants for CEPEF-4. STUDY DESIGN: Online questionnaire survey. METHODS: An online questionnaire was prepared and the link distributed internationally to veterinarians possibly performing equine anaesthesia, using emails, posters, flyers and an editorial. The questionnaire included 52 closed, semiclosed and open questions divided into 8 subgroups: demographic data, anaesthetist, anaesthesia management (preoperative, technical equipment, monitoring, drugs, recovery), areas of improvements and risks and motivation for participation in CEPEF-4. Descriptive statistics and Chi-squared tests for comparison of categorical variables were performed. RESULTS: A total of 199 questionnaires were completed by veterinarians from 14 different countries. Of the respondents, 43% worked in private hospitals, 36% in private practices and 21% in university teaching hospitals. In 40 institutions (23%) there was at least one diplomate of the European or American colleges of veterinary anaesthesia and analgesia on staff. Individual respondents reported routinely employ the following anaesthesia monitoring modalities: electrocardiography (80%), invasive arterial blood pressures (70%), pulse oximetry (60%), capnography (55%), arterial blood gases (47%), composition of inspired and expired gases (45%) and body temperature (35%). Drugs administered frequently or routinely as part of a standard protocol were: acepromazine (44%), xylazine (68%), butorphanol (59%), ketamine (96%), diazepam (83%), isoflurane (76%), dobutamine (46%), and, as a nonsteroidal anti-inflammatory drug, phenylbutazone (73%) or flunixin meglumine (66%). Recovery was routinely assisted by 40%. The main factors perceived by the respondents to affect outcome of equine anaesthesia were the preoperative health status of the animal and training of the anaesthetist. CONCLUSIONS: Current practice in equine anaesthesia varies widely, and the study has highlighted important topics relevant for designing a future prospective multicentre cohort study (CEPEF-4). The Summary is available in Chinese - see Supporting information.

Impact of anesthesia on cancer recurrence.

Surgery remains the mainstay treatment in the majority of solid cancers. Anesthetics and analgesics used during the perioperative period may modulate the innate and adaptive immune system, inflammation and angiogenesis, and have a direct effect on cancer cells that could ultimately modify oncological outcomes. For instance, volatile anesthetics and opioid analgesics have shown predominantly pro-tumor effects, while propofol, non-steroid anti-inflammatory drugs have mostly anticancer effects. Researchers have been especially interested in investigating the association between the use of regional anesthesia techniques and the postoperative survival of patients with cancers. Since the results of the current retrospective studies are conflicting, several researchers are conducting prospective randomized trials.

The role of nicotinic acetylcholine receptors in the mechanisms of anesthesia.

Nicotinic acetylcholine receptors are members of the ligand-gated ion channel superfamily, that includes also gamma-amino-butiric-acid(A), glycine, and 5-hydroxytryptamine(3) receptors. Functional nicotinic acetylcholine receptors result from the association of five subunits each contributing to the pore lining. The major neuronal nicotinic acetylcholine receptors are heterologous pentamers of alpha4beta2 subunits (brain), or alpha3beta4 subunits (autonomic ganglia). Another class of neuronal receptors that are found both in the central and peripheral nervous system is the homomeric alpha7 receptor. The muscle receptor subtypes comprise of alphabetadeltagamma (embryonal) or alphabetadeltaepsilon (adult) subunits. Although nicotinic acetylcholine receptors are not directly involved in the hypnotic component of anesthesia, it is possible that modulation of central nicotinic transmission by volatile agents contributes to analgesia. The main effect of anesthetic agents on nicotinic acetylcholine receptors is inhibitory. Volatile anesthetics and ketamine are the most potent inhibitors both at alpha4beta2 and alpha3beta4 receptors with clinically relevant IC(50) values. Neuronal nicotinic acetylcholine receptors are more sensitive to anesthetics than their muscle counterparts, with the exception of the alpha7 receptor. Several intravenous anesthetics such as barbiturates, etomidate, and propofol exert also an inhibitory effect on the nicotinic acetylcholine receptors, but only at concentrations higher than those necessary for anesthesia. Usual clinical concentrations of curare cause competitive inhibition of muscle nicotinic acetylcholine receptors while higher concentrations may induce open channel blockade. Neuronal nAChRs like alpha4beta2 and alpha3beta4 are inhibited by atracurium, a curare derivative, but at low concentrations the alpha4beta2 receptor is activated. Inhibition of sympathetic transmission by clinically relevant concentrations of some anesthetic agents is probably one of the factors involved in arterial hypotension during anesthesia.

[Effects of anesthetic agents on intracranial pressure]. / Effects des agents anesthésiques sur la pression intracrânienne.

Barbiturates, etomidate and propofol decrease cerebral blood flow (CBF), mediated by a decrease in cerebral metabolism, thus decreasing intracranial pressure (ICP). As the reduction in CBF is secondary to a decrease in cerebral metabolism, these agents will have little effect on CBF or ICP in patients without active cerebral metabolic activity. Ketamine is usually not administered for the anaesthetic management of patients at risk of intracranial hypertension because of the reported increases in cerebral metabolism, CBF and ICP. The increase in CBF, however, may be partly mediated by a sympathetically induced increase in blood pressure and partly by a simultaneous increase in PaCO2 in spontaneously breathing patients. More recent studies report no increase in ICP or flow when ventilation is controlled or when other agents are associated. There is renewed interest in ketamine because it blocks excitatory amino acid receptors in the brain. Synthetic opioids including fentanyl, sufentanil, and alfentanil have been reported to cause an increase in ICP in patients with various intracranial lesions. When blood pressure was supported, no clinically relevant increase in ICP or flow velocity with alfentanil or sufentanil was observed. Thus, the increase in ICP reported with these agents may be related to the compensatory autoregulation-mediated vasodilation, underscoring the importance of administering these agents carefully to avoid systemic hypotension. Halothane consistently increases CBF and should not be used in patients with increased ICP. In contrast, isoflurane does not cause increase in CBF at concentrations below 1 to 1.5 MAC, although the effects on cerebral blood volume are less clear. Desflurane and sevoflurane have similar effects. CO2 reactivity is preserved with all inhaled agents. In patients with increased ICP however, it would be preferable to avoid these agents or to administer very low doses.

[Possibilities and limitations of intravenous anesthesia]. / Möglichkeiten und Grenzen der intravenösen Anästhesie.

The increasing importance of intravenous anaesthesia is based on two developments, namely the synthesis of substances capable of acting selectively and over the short term, and which are rapidly eliminated (good control), and a desire on the part of the anaesthetist to have an anaesthetic whose actions can be controlled in various ways. Efforts in this area are aimed at ensuring not only a minimum of stressing of organs by the anaesthetic, but also a minimisation of risks during the intra-operative phase, and a non-problematic maximally pleasant post-operative course. There are two problems that militate against the realization of these objectives. Although the substances presented here ideally permit the realization of some of these aims, at the same time they are associated with side effects that prevent their use from ever being completely non-problematical, and which should always prompt the exercise of particular care when employing these medications. In addition, the differentiable control made possible by the use of these drugs is (partly) offset by inadequate monitoring with respect to the qualities of the anaesthetic--a fact that modifies the potential advantages of intravenous anaesthesia.

[Botulinum toxin: clinical uses and anesthetic implications]. / Toxina botulínica: usos clínicos e implicaciones anestésicas.

Botulinum toxin, a neurotoxin responsible for botulism, is at present used to treat anomalous muscle contractions. Administration to children and relatively uncooperative patients requires general anesthesia, which should be selected taking into consideration the special characteristics of the surgical procedure and the possible interactions of anesthetic drugs and the toxin.

Into the land of Nod: drugs used during anesthesia in day surgery.

This paper lists and describes some of the drugs used during anesthesia in a Day Surgery Operating Room. The classification, action and implications of these drugs are addressed. The discussion is presented under the drug classes as Narcotic Analgesics/Opioids Antagonists, Opiate Antagonists, Induction Agents, Muscle Relaxants/Neuromuscular Blocking Agents, Inhalation Anesthetics, Cholinesterase Inhibitors Anticholinesterases/Parasymphathomimetics, Anticholinergics/Antimuscarinics/Parasympatholytics, and Antiemitics.