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
BACKGROUND: This study compares outcomes at a hospital-linked, physician-led, birthing center to a traditional hospital labor and delivery service. METHODS: Using de-identified electronic medical records, a retrospective cohort design was employed to evaluate 32,174 singleton births during 1998-2005. RESULTS: Compared with hospital service, birth care center delivery was associated with a lower rate of cesarean sections (adjusted Relative Risk = 0.73, 95% confidence interval 0.59-0.91; p < 0.001) without an increased rate of operative vaginal delivery (adjusted Relative Risk = 1.04, 95% confidence interval 0.97-1.13; p = 0.25) and a higher initiation of breastfeeding (adjusted Relative Risk = 1.28, 95% confidence interval 1.25-1.30; p ≤ 0.001). A maternal length of stay greater than 72 hours occurred less frequently in the birth care center (adjusted Relative Risk = 0.60, 95% confidence interval 0.55-0.66; p < 0.001). Comparing only women without major obstetrical risk factors, the differences in outcomes were reduced but not eliminated. Adverse maternal and infant outcomes were not increased at the birth care center. CONCLUSION: A hospital-linked, physician-led, birth care center has the potential to lower rates of cesarean sections without increasing rates of operative vaginal delivery or other adverse maternal and infant outcomes.