RESUMO
Despite successfully utilizing anesthetics for over 150 years, the mechanism of action remains relatively unknown. Recent studies have shown promising results, but due to the complex interactions between anesthetics and their targets, there remains a clear need for further mechanistic research. We know that lipophilicity is directly connected to anesthetic potency since lipid solubility relates to anesthetic partition into the membrane. However, clinically relevant concentrations of anesthetics do not significantly affect lipid bilayers but continue to influence various molecular targets. Lipid rafts are derived from liquid-ordered phases of the plasma membrane that contain increased concentrations of cholesterol and sphingomyelin and act as staging platforms for membrane proteins, including ion channels. Although anesthetics do not perturb membranes at clinically relevant concentrations, they have recently been shown to target lipid rafts. In this review, we summarize current research on how different types of anesthetics-local, inhalational, and intravenous-bind and affect both lipid rafts and voltage-gated sodium channels, one of their major targets, and how those effects synergize to cause anesthesia and analgesia. Local anesthetics block voltage-gated sodium channel pores while also disrupting lipid packing in ordered membranes. Inhalational anesthetics bind to the channel pore and the voltage-sensing domain while causing an increase in the number, size, and diameter of lipid rafts. Intravenous anesthetics bind to the channel primarily at the voltage-sensing domain and the selectivity filter, while causing lipid raft perturbation. These changes in lipid nanodomain structure possibly give proteins access to substrates that have translocated as a result of these structural alterations, resulting in lipid-driven anesthesia. Overall, anesthetics can impact channel activity either through direct interaction with the channel, indirectly through the lipid raft, or both. Together, these result in decreased sodium ion flux into the cell, disrupting action potentials and producing anesthetic effects. However, more research is needed to elucidate the indirect mechanisms associated with channel disruption through the lipid raft, as not much is known about anionic lipid products and their influence over voltage-gated sodium channels. Anesthetics' effect on S-palmitoylation, a promising mechanism for direct and indirect influence over voltage-gated sodium channels, is another auspicious avenue of research. Understanding the mechanisms of different types of anesthetics will allow anesthesiologists greater flexibility and more specificity when treating patients.
RESUMO
Our hospital adopted universal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing for labor and delivery patients in April 2020. The primary aim of this study was to determine the number of subjects from April 1, 2020, to July 31, 2020, who had laboratory-confirmed SARS-CoV-2 infection, and the secondary aims were to report demographic and clinical data for subjects with and without SARS-CoV-2 infection and the time from SARS-CoV-2 test collection to result for tests administered in the hospital. A total of 898 subjects had either vaginal or cesarean deliveries with a gestational age of >20 weeks during the study period. Of this group, 746 subjects underwent SARS-CoV-2 testing, and 16 had a positive test result. Four of the 16 subjects with laboratory-confirmed SARS-CoV-2 infection had documented symptoms at the time of admission. The difference in cohort size was too large to make a meaningful statistical comparison in demographic and clinical data between those with positive vs negative SARS-CoV-2 test results. The median time from SARS-CoV-2 test collection to result decreased from 239 minutes in April 2020 to 119 minutes in July 2020. Universal SARS-CoV-2 testing revealed a 2.1% positivity rate during our study period.