Anesthesiology
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Recent studies of anesthetic-induced unconsciousness in humans have focused predominantly on the intravenous drug propofol and have identified anterior dominance of alpha rhythms and frontal phase-amplitude coupling patterns as neurophysiological markers. However, it is unclear whether the correlates of propofol-induced unconsciousness are generalizable to inhaled anesthetics, which have distinct molecular targets and which are used more commonly in clinical practice. ⋯ In humans, sevoflurane-induced unconsciousness is not correlated with anteriorization of alpha and related cross-frequency patterns, but rather by a disruption of phase-amplitude coupling in the parietal region and phase-phase relationships across the cortex.
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Several retrospective studies suggest that perioperative care and anesthetic management for cancer resection may influence cancer recurrence or patient survival. Various intraoperative techniques such as paravertebral blocks, decreased opioid use, immunomodulation, and perioperative antiinflammatory administration, have previously been assessed for improved patient survival. The aim of this study was to assess associations between perioperative management and survival in patients undergoing resection of pancreatic adenocarcinoma. ⋯ The authors report an association between perioperative dexamethasone administration and improved survival in human pancreatic adenocarcinoma patients. An association between use of epidural anesthesia during primary pancreatic cancer surgery and prolonged survival was also observed. Previously identified associations between perioperative blood transfusions and poor tumor histologic grade and decreased survival were confirmed. Further investigations regarding the use of perioperative dexamethasone and neuraxial anesthesia in this patient population are warranted.
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There is an unmet clinical need to develop a pharmacological therapy to counter opioid-induced respiratory depression without interfering with analgesia or behavior. Several studies have demonstrated that 5-HT1A receptor agonists alleviate opioid-induced respiratory depression in rodent models. However, there are conflicting reports regarding their effects on analgesia due in part to varied agonist receptor selectivity and presence of anesthesia. Therefore the authors performed a study in rats with befiradol (F13640 and NLX-112), a highly selective 5-HT1A receptor agonist without anesthesia. ⋯ The reversal of opioid-induced respiratory depression and sedation by befiradol in adult rats was robust, whereas involved mechanisms are unclear. However, there were adverse concomitant decreases in fentanyl-induced analgesia and altered baseline ventilation, nociception, and behavior.
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The development of novel anesthetics has historically been a process of combined serendipity and empiricism, with most recent new anesthetics developed via modification of existing anesthetic structures. ⋯ The authors demonstrate the first use of a high-throughput screen to successfully identify a novel anesthetic chemotype and show mammalian anesthetic activity for members of that chemotype.