Anesthesiology
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Randomized Controlled Trial
Analgesic and Respiratory Depressant Effects of R-dihydroetorphine: A Pharmacokinetic-Pharmacodynamic Analysis in Healthy Male Volunteers.
There is an ongoing need for potent opioids with less adverse effects than commonly used opioids. R-dihydroetorphine is a full opioid receptor agonist with relatively high affinity at the μ-, δ- and κ-opioid receptors and low affinity at the nociception/orphanin FQ receptor. The authors quantified its antinociceptive and respiratory effects in healthy volunteers. The authors hypothesized that given its receptor profile, R-dihydroetorphine will exhibit an apparent plateau in respiratory depression, but not in antinociception. ⋯ Over the dose range studied, R-dihydroetorphine exhibited a plateau in respiratory depression, but not in analgesia. Whether these experimental advantages extrapolate to the clinical setting and whether analgesia has no plateau at higher concentrations than investigated requires further studies.
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Transgenic mouse studies suggest that γ-aminobutyric acid type A (GABAA) receptors containing β3 subunits mediate important effects of etomidate, propofol, and pentobarbital. Zebrafish, recently introduced for rapid discovery and characterization of sedative-hypnotics, could also accelerate pharmacogenetic studies if their transgenic phenotypes reflect those of mammals. The authors hypothesized that, relative to wild-type, GABAA-β3 functional knock-out (β3) zebrafish would show anesthetic sensitivity changes similar to those of β3 mice. ⋯ Global β3 zebrafish are selectively insensitive to the same few sedative-hypnotics previously reported in β3 transgenic mice, indicating phylogenetic conservation of β3-containing GABAA receptors as anesthetic targets. Transgenic zebrafish are potentially valuable models for sedative-hypnotic mechanisms research.
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Commercial applications of artificial intelligence and machine learning have made remarkable progress recently, particularly in areas such as image recognition, natural speech processing, language translation, textual analysis, and self-learning. Progress had historically languished in these areas, such that these skills had come to seem ineffably bound to intelligence. However, these commercial advances have performed best at single-task applications in which imperfect outputs and occasional frank errors can be tolerated. ⋯ It embodies a requirement for high reliability, and a pressured cycle of interpretation, physical action, and response rather than any single cognitive act. This review covers the basics of what is meant by artificial intelligence and machine learning for the practicing anesthesiologist, describing how decision-making behaviors can emerge from simple equations. Relevant clinical questions are introduced to illustrate how machine learning might help solve them-perhaps bringing anesthesiology into an era of machine-assisted discovery.
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Nerve blocks improve early pain after ambulatory shoulder surgery; impact on postdischarge outcomes is poorly described. Our objective was to measure the association between nerve blocks and health system outcomes after ambulatory shoulder surgery. ⋯ In ambulatory shoulder surgery, nerve blocks were not associated with a significant difference in adverse postoperative outcomes. Costs were statistically higher with a block, but this increase is not likely clinically relevant.
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Sevoflurane with its antiinflammatory properties has shown to decrease mortality in animal models of sepsis. However, the underlying mechanism of its beneficial effect in this inflammatory scenario remains poorly understood. Macrophages play an important role in the early stage of sepsis as they are tasked with eliminating invading microbes and also attracting other immune cells by the release of proinflammatory cytokines such as interleukin-1β, interleukin-6, and tumor necrosis factor-α. Thus, the authors hypothesized that sevoflurane mitigates the proinflammatory response of macrophages, while maintaining their bactericidal properties. ⋯ Sevoflurane enhances phagocytosis of bacteria by lipopolysaccharide-challenged macrophages in vitro and in vivo via an inducible NO synthase-dependent mechanism. Thus, sevoflurane potentiates bactericidal and antiinflammatory host-defense mechanisms in endotoxemia.