Anesthesia and analgesia
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Anesthesia and analgesia · Nov 2016
ReviewRegulating the Efficacy of Inhibition Through Trafficking of γ-Aminobutyric Acid Type A Receptors.
Trafficking of anesthetic-sensitive receptors within the plasma membrane, or from one cellular component to another, occurs continuously. Changes in receptor trafficking have implications in altering anesthetic sensitivity. γ-Aminobutyric acid type A receptors (GABAARs) are anion-permeable ion channels and are the major class of receptor in the adult mammalian central nervous system that mediates inhibition. GABAergic signaling allows for precise synchronized firing of action potentials within brain circuits that is critical for cognition, behavior, and consciousness. ⋯ Neuronal activity, posttranslational modifications, and some naturally occurring and synthetic compounds can influence the expression and trafficking of GABAARs. In this article, we review GABAARs, their trafficking, and how phosphorylation of GABAAR subunits can influence the surface expression and function of the receptor. Ultimately, alterations of GABAAR trafficking could modify anesthetic end points, both unintentionally through pathologic processes but potentially as a therapeutic target to adjust anesthetic-sensitive GABAARs.
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Anesthesia and analgesia · Nov 2016
ReviewShedding Light on Anesthetic Mechanisms: Application of Photoaffinity Ligands.
Anesthetic photoaffinity ligands have had an increasing presence within anesthesiology research. These ligands mimic parent general anesthetics and allow investigators to study anesthetic interactions with receptors and enzymes; identify novel targets; and determine distribution within biological systems. ⋯ In this review, we examine all aspects of the current methodologies, including ligand design, characterization, and deployment. Finally we offer points of consideration and highlight the future outlook as more photoaffinity ligands emerge within the field.
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Anesthesia and analgesia · Nov 2016
ReviewRecent Insights Into Molecular Mechanisms of Propofol-Induced Developmental Neurotoxicity: Implications for the Protective Strategies.
Mounting evidence has demonstrated that general anesthetics could induce developmental neurotoxicity, including acute widespread neuronal cell death, followed by long-term memory and learning abnormalities. Propofol is a commonly used intravenous anesthetic agent for the induction and maintenance of anesthesia and procedural and critical care sedation in children. Compared with other anesthetic drugs, little information is available on its potential contributions to neurotoxicity. ⋯ We then discuss the mechanism of propofol-induced developmental neurotoxicity, such as increased cell death in neurons and oligodendrocytes, dysregulation of neurogenesis, abnormal dendritic development, and decreases in neurotrophic factor expression. Recent findings of complex mechanisms of propofol action, including alterations in microRNAs and mitochondrial fission, are discussed as well. An understanding of the toxic effect of propofol and the underlying mechanisms may help to develop effective novel protective or therapeutic strategies for avoiding the neurotoxicity in the developing human brain.
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Anesthesia and analgesia · Nov 2016
ReviewSCAI/CCAS/SPA Expert Consensus Statement for Anesthesia and Sedation Practice: Recommendations for Patients Undergoing Diagnostic and Therapeutic Procedures in the Pediatric and Congenital Cardiac Catheterization Laboratory.
Current practice of sedation and anesthesia for patients undergoing pediatric and congenital cardiac catheterization laboratory (PCCCL) procedures is known to vary among institutions, a multi-society expert panel with representatives from the Congenital Heart Disease Council of the Society for Cardiovascular Angiography and Interventions, the Society for Pediatric Anesthesia and the Congenital Cardiac Anesthesia Society was convened to evaluate the types of sedation and personnel necessary for procedures performed in the PCCCL. The goal of this panel was to provide practitioners and institutions performing these procedures with guidance consistent with national standards and to provide clinicians and institutions with consensus-based recommendations and the supporting references to encourage their application in quality improvement programs. ⋯ This expert consensus statement has adhered to these principles for optimal management of patients requiring sedation and anesthesia. What follows are recommendations for patient monitoring in the PCCCL regardless of whether minimal or no sedation is being used or general anesthesia is being provided by an anesthesiologist.
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Anesthesia and analgesia · Nov 2016
ReviewDisconnecting Consciousness: Is There a Common Anesthetic End Point?
A quest for a systems-level neuroscientific basis of anesthetic-induced loss and return of consciousness has been in the forefront of research for the past 2 decades. Recent advances toward the discovery of underlying mechanisms have been achieved using experimental electrophysiology, multichannel electroencephalography, magnetoencephalography, and functional magnetic resonance imaging. By the careful dosing of various volatile and IV anesthetic agents to the level of behavioral unresponsiveness, both specific and common changes in functional and effective connectivity across large-scale brain networks have been discovered and interpreted in the context of how the synthesis of neural information might be affected during anesthesia. ⋯ The critical neural events that account for the transition between responsive and unresponsive states should be assessed at similar anesthetic doses just below and above the loss or return of responsiveness. There will also be a need to identify a robust, sensitive, and reliable measure of information transfer. Ultimately, finding a behavior-independent measure of subjective experience that can track covert cognition in unresponsive subjects and a delineation of causal factors versus correlated events will be essential to understand the neuronal basis of human consciousness and unconsciousness.