Anesthesiology
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Cyclopropyl-methoxycarbonyl metomidate (CPMM, also known as ABP-700) is a second-generation "soft" (i.e., metabolically labile) etomidate analogue. The purpose of this study was to characterize CPMM's pharmacology in beagle dogs in preparation for potential first in human phase 1 clinical trials. ⋯ The studies in dogs confirm that CPMM has hypnotic and adrenocortical recovery profiles that are superior than those of etomidate, supporting the continued development of CPMM as a clinical sedative-hypnotic to be used as a single bolus and by continuous infusion to induce and maintain general anesthesia or procedural sedation.
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Myeloid differentiation factor 88 (MyD88) is an adaptor molecule critical for host innate immunity. Studies have shown that signaling via MyD88 contributes to cytokine storm, cardiac dysfunction, and high mortality during endotoxin shock.However, the specific contribution of MyD88 signaling of immune and cardiac origins to endotoxin shock remains unknown. ⋯ Both cardiomyocyte- and myeloid-MyD88 signaling play a role in cardiac dysfunction and mortality during endotoxin shock. Myeloid-MyD88 signaling plays a predominant role in systemic and cardiac inflammation after endotoxin challenge.
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Toll-like receptor 4 (TLR4), the receptor for endotoxin, mediates hyperinflammatory response and contributes to high mortality during both endotoxin shock and severe sepsis. However, little is known about the role of TLR4 in the pathogenesis of low-grade polymicrobial sepsis, which is often associated with immunosuppression. ⋯ TLR4 plays an essential role in host defense against low-grade polymicrobial sepsis by mediating neutrophil migratory/phagocytic functions, attenuating inflammation, reducing reactive oxygen species generation, and enhanced bacterial clearance.
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Process improvement in healthcare delivery settings can be difficult, even when there is consensus among clinicians about a clinical practice or desired outcome. Airway management is a medical intervention fundamental to the delivery of anesthesia care. Like other medical interventions, a detailed description of the management methods should be documented. Despite this expectation, airway documentation is often insufficient. The authors hypothesized that formal adoption of process improvement methods could be used to increase the rate of "complete" airway management documentation. ⋯ Systematic application of process improvement methodologies can improve airway documentation and may be similarly effective in improving other areas of anesthesia clinical practice.
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The effects of inhaled anesthetics on the developing brain are studied using neonatal rodents exposed to fractions of minimum alveolar concentration (to avoid cardiorespiratory compromise). However, these fractions cannot be assumed to be equipotent. Xenon's anesthetic and neuroprotective properties warrant investigation in these models. Therefore, equipotent, subanesthetic concentrations of inhaled anesthetics are needed. ⋯ The authors report equipotent subanesthetic concentrations of sevoflurane and xenon in neonatal rats with preserved cardiopulmonary function. This may be useful in designing neonatal rodent models of anesthesia.