Search

Background: Ischemic preconditioning is an important intrinsic mechanism for neuroprotection. Preconditioning can also be achieved by exposure of neurons to K+ channel-opening drugs that act on adenosine triphosphate-sensitive K+ (K(ATP)) channels. However, these agents do not readily cross the blood-brain barrier. Inhalational anesthetics which easily partition into brain have been shown to precondition various tissues. Here, the authors explore the neuronal preconditioning effect of modern inhalational anesthetics and investigate their effects on K(ATP) channels.Methods: Neuronal-glial cocultures were exposed to inhalational anesthetics in a preconditioning paradigm, followed by oxygen-glucose deprivation. Increased cell survival due to preconditioning was quantified with the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide reduction test. Recombinant plasmalemmal K(ATP) channels of the main neuronal type (Kir6.2/SUR1) were expressed in HEK293 cells, and the effects of anesthetics were evaluated in whole cell patch clamp recordings.Results: Both sevoflurane and the noble gas xenon preconditioned neurons at clinically used concentrations. The effect of sevoflurane was independent of K(ATP) channel activation, whereas the effect of xenon required the opening of plasmalemmal K(ATP) channels. Recombinant K(ATP) channels were activated by xenon but inhibited by halogenated volatiles. Modulation of mitochondrial K-ATP channels did not affect the activity of K(ATP) channels, thus ruling out an indirect effect of volatiles via mitochondrial channels.Conclusions: The preconditioning properties of halogenated volatiles cannot be explained by their effect on K(ATP) channels, whereas xenon preconditioning clearly involves the activation of these channels. Therefore, xenon might mimic the intrinsic mechanism of ischemic preconditioning most closely. This, together with its good safety profile, might suggest xenon as a viable neuroprotective agent in the clinical setting. [ABSTRACT FROM AUTHOR]

Background: Surgery is accompanied by a systemic inflammatory response that may presage delirium in susceptible individuals. Little is known about the trajectory of plasma proinflammatory cytokines and their potential associations with postoperative delirium (POD). The current study longitudinally assessed both pro and anti-inflammatory plasma cytokine response and development of POD in older surgical patients to investigate associations with individual and/or clusters of cytokines that may indicate pathogenic mechanisms., Methods: A prospective longitudinal study sought to enroll patients >60 years old who were scheduled for major lower limb surgery under general anesthesia. Blood was obtained preoperatively and postoperatively from day 1 through postoperative day 4 for measurement of plasma interleukin-1β (IL-1β), IL-2, IL-4, IL-6, soluble IL-6 receptor (sIL-6R), IL-10, and tumor necrosis factor-α (TNF-α). Participants were assessed for POD twice daily for 4 days using the confusion assessment method. Trajectory of postoperative changes in plasma cytokines was determined by a group-based trajectory modeling analysis that was informed by distinct cytokines identified by time-dependent Cox regression model., Results: One hundred eighty-eight patients were assessed for eligibility of whom 129 underwent major surgery and 126 had complete datasets for final analysis. POD was diagnosed in 31 of 126 patients (24.6%). Time-dependent Cox regression model identified that higher IL-6 and sIL-6R levels were associated with higher risk of developing POD. A two-cluster model (stable lower and fluctuating higher levels) was considered to be the most statistically appropriate model for IL-6 and sIL-6R trajectory. More participants with fluctuating higher IL-6 were delirious (73.3% vs 18.0%, P = .001) as were those with fluctuating higher sIL-6R (81.3% vs 16.4%, P = .001)., Conclusions: As higher IL-6 and sIL-6R levels were significantly associated with higher risk of POD and the combination is required for IL-6 trans-signaling, it is possible that activation of this pathway may be associated with POD. Furthermore, it will be important to determine whether high levels of the combination of IL-6 and sIL-6R can be an early biomarker for the subsequent development of POD., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2022 International Anesthesia Research Society.)

Objectives: Clinical trials evaluating the safety and effectiveness of sedative medication use in critically ill adults undergoing mechanical ventilation differ considerably in their methodological approach. This heterogeneity impedes the ability to compare results across studies. The Sedation Consortium on Endpoints and Procedures for Treatment, Education, and Research Recommendations convened a meeting of multidisciplinary experts to develop recommendations for key methodologic elements of sedation trials in the ICU to help guide academic and industry clinical investigators., Design: A 2-day in-person meeting was held in Washington, DC, on March 28-29, 2019, followed by a three-round, online modified Delphi consensus process., Participants: Thirty-six participants from academia, industry, and the Food and Drug Administration with expertise in relevant content areas, including two former ICU patients attended the in-person meeting, and the majority completed an online follow-up survey and participated in the modified Delphi process., Measurements and Main Results: The final recommendations were iteratively refined based on the survey results, participants' reactions to those results, summaries written by panel moderators, and a review of the meeting transcripts made from audio recordings. Fifteen recommendations were developed for study design and conduct, subject enrollment, outcomes, and measurement instruments. Consensus recommendations included obtaining input from ICU survivors and/or their families, ensuring adequate training for personnel using validated instruments for assessments of sedation, pain, and delirium in the ICU environment, and the need for methodological standardization., Conclusions: These recommendations are intended to assist researchers in the design, conduct, selection of endpoints, and reporting of clinical trials involving sedative medications and/or sedation protocols for adult ICU patients who require mechanical ventilation. These recommendations should be viewed as a starting point to improve clinical trials and help reduce methodological heterogeneity in future clinical trials., Competing Interests: The views expressed in this article are those of the authors, none of whom have financial conflicts of interest specifically related to the issues discussed in this article. At the time of the meeting (March 28–29, 2019) on which this article is based, several participants were employed by a pharmaceutical company or had received consulting fees or honoraria from one or more pharmaceutical or device companies. Meeting participants of this article who were not employed by industry at the time of the meeting received (or their Universities received) travel stipends, hotel accommodations, and meals during the meeting from the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks public-private partnership with the Food and Drug Administration. Drs. Ward, Aitken, Colantuoni, Maze, and Needham received funding from Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, and Networks (ACTTION). Dr. Ward received support for article research from the University of Rochester Maine Medical Center Spectrum Medical Partners. Dr. Absalom’s institution received funding from The Medicines Company, Carefusion (BD), and Rigel; he received support for article research from Philips, Janssen Pharma, Johnson & Johnson, Ever Pharma, Orion, and Paion. Drs. Aitken, Brown, and Coursin received funding from Innovations Consulting Group LLC. Dr. Aitken also received funding from Elsevier Australia. Dr. Balas’ institution received funding from the National Institutes of Health (NIH), the National Heart, Lung, and Blood Institute, AACN research grant; she received funding from H3C and received support for article research from the NIH. Dr. Colantuoni received support for article research from ACTTION. Dr. Dexter received funding from the Division of Management Consulting of the University of Iowa’s Department of Anesthesia. Dr. Dworkin’s institution received funding from the U.S. Food and Drug Administration (FDA); he received funding from Abide, Acadia, Adynxx, Analgesic Solutions, Aptinyx, Aquinox, Asahi Kasei, Astellas, AstraZeneca, Biogen, Biohaven, Boston Scientific, Braeburn, Celgene, Centrexion, Chromocell, Clexio, Collegium, Concert, Coronado, Daiichi Sankyo, Decibel, Dong-A, Editas, Eli Lilly, Eupraxia, Glenmark, Grace, Hope, Hydra, Immune, Johnson & Johnson, Lotus Clinical Research, Mainstay, Medavante, Merck, Neumentum, Neurana, NeuroBo, Novaremed, Novartis, NSGene, Olatec, Periphagen, Pfizer, Phosphagenics, Quark, Reckitt Benckiser, Regenacy, Relmada, Sanifit, Scilex, Semnur, SK Life Sciences, Sollis, Spinifex, Syntrix, Teva, Thar, Theranexus, Trevena, Vertex, and Vizuri. Dr. Girard received funding from Haisco Pharmaceutical. Dr. Hopkins’ institution received funding from Intermountain Medical and Research Foundation. Dr. Maze received funding from the University of California Office of the President and Cambridge University Press; he received support for article research from the NIH. Dr. Needham received funding from the FDA, Haisco-USA Pharmaceuticals, GlaxoSmithKline, and Novartis Pharma; he disclosed he is a principal investigator on a NIH-funded, multicentered randomized trial (R01HL132887) funded by Baxter Healthcare Corporation and Reck Medical Devices. Dr. Pandharipande’s institution received funding from Pfizer. Dr. Shehabi’s institution received funding from Orion Pharma and Pfizer; he received funding from Pfizer, Orion Pharma, Abbott Laboratories, and Ever Pharma. Dr. Sun received funding from UpToDate; she disclosed she is the Editor in Chief for UpToDate/Anesthesiology. Dr. Tung received funding from Anesthesia and Analgesia. Dr. Urman’s institution received funding from Medtronic/Covidien and AcelRx; he received funding from Merck, Sandoz, Heron, Takeda, and Pfizer. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

Background: Clinical studies have shown that dexmedetomidine ameliorates cognitive decline in both the postoperative and critical care settings. This study determined the mechanism(s) for the benefit provided by dexmedetomidine in a medical illness in mice induced by lipopolysaccharide., Methods: Cognitive decline, peripheral and hippocampal inflammation, blood-brain barrier permeability, and inflammation resolution were assessed in male mice. Dexmedetomidine was administered in the presence of lipopolysaccharide and in combination with blockers. Cultured macrophages (RAW 264.7; BV-2) were exposed to lipopolysaccharide ± dexmedetomidine ± yohimbine; tumor necrosis factor α release into the medium and monocyte NFκB activity was determined., Results: In vivo, lipopolysaccharide-induced cognitive decline and inflammation (mean ± SD) were reversed by dexmedetomidine (freezing time, 55.68 ± 12.31 vs. 35.40 ± 17.66%, P = 0.0286, n = 14; plasma interleukin [IL]-1β: 30.53 ± 9.53 vs. 75.68 ± 11.04 pg/ml, P < 0.0001; hippocampal IL-1β: 3.66 ± 1.88 vs. 28.73 ± 5.20 pg/mg, P < 0.0001; n = 8), which was prevented by α2 adrenoceptor antagonists. Similar results were found in 12-month-old mice. Lipopolysaccharide also increased blood-brain barrier leakage, inflammation-resolution orchestrator, and proresolving and proinflammatory mediators; each lipopolysaccharide effect was attenuated by dexmedetomidine, and yohimbine prevented dexmedetomidine's attenuating effect. In vitro, lipopolysaccharide-induced tumor necrosis factor α release (RAW 264.7: 6,308.00 ± 213.60 vs. 7,767.00 ± 358.10 pg/ml, P < 0.0001; BV-2: 1,075.00 ± 40.41 vs. 1,280.00 ± 100.30 pg/ml, P = 0.0003) and NFκB-p65 activity (nuclear translocation [RAW 264.7: 1.23 ± 0.31 vs. 2.36 ± 0.23, P = 0.0031; BV-2: 1.08 ± 0.26 vs. 1.78 ± 0.14, P = 0.0116]; phosphorylation [RAW 264.7: 1.22 ± 0.40 vs. 1.94 ± 0.23, P = 0.0493; BV-2: 1.04 ± 0.36 vs. 2.04 ± 0.17, P = 0.0025]) were reversed by dexmedetomidine, which was prevented by yohimbine., Conclusions: Preclinical studies suggest that the cognitive benefit provided by dexmedetomidine in mice administered lipopolysaccharide is mediated through α2 adrenoceptor-mediated anti-inflammatory pathways.

The purpose of this article is to provide a succinct summary of the different experimental approaches that have been used in preclinical postoperative cognitive dysfunction research, and an overview of the knowledge that has accrued. This is not intended to be a comprehensive review, but rather is intended to highlight how the many different approaches have contributed to our understanding of postoperative cognitive dysfunction, and to identify knowledge gaps to be filled by further research. The authors have organized this report by the level of experimental and systems complexity, starting with molecular and cellular approaches, then moving to intact invertebrates and vertebrate animal models. In addition, the authors' goal is to improve the quality and consistency of postoperative cognitive dysfunction and perioperative neurocognitive disorder research by promoting optimal study design, enhanced transparency, and "best practices" in experimental design and reporting to increase the likelihood of corroborating results. Thus, the authors conclude with general guidelines for designing, conducting and reporting perioperative neurocognitive disorder rodent research.

Objectives: The aim was to compare the long-term outcomes of low-dose dexmedetomidine versus placebo in a randomized controlled trial (ChiCTR-TRC-10000802)., Background: Low-dose dexmedetomidine infusion decreased delirium occurrence within 1 week after surgery in elderly admitted to the intensive care unit (ICU) after noncardiac surgery, but the long-term outcome of this intervention is unknown., Methods: Patients or their family members were telephone-interviewed for a 3-year follow-up data collection of survival, cognitive function assessed with the modified Telephone Interview for Cognitive Status, and quality of life evaluated with the World Health Organization Quality of Life., Results: Of the 700 patients, 23 (3.3%) were lost at 3-year follow-up. The 3-year overall survival was not statistically different between the dexmedetomidine and placebo groups [114 deaths vs 122/350; hazard ratio (HR) 0.87, 95% confidence interval (CI) 0.68-1.13, P = 0.303]. The survival rates at 6 months, 1 year, and 2 years were significantly higher in the dexmedetomidine than in the placebo group (rate difference of 5.2%, 5.3%, and 6.7% respectively; all P < 0.05). The remaining 98.4% (434/441) 3-year survivors, the dexmedetomidine group, had significantly better cognitive function (mean difference 4.7, 95% CI 3.8-5.6, P < 0.0001) and quality of life (physical domain: 13.6 [10.6-16.6]; psychological domain: 15.2 [12.5-18.0]; social relationship domain: 8.1 [5.5-10.7]; environment domain: 13.3 [10.9-15.7]; all P < 0.0001) than in the placebo group., Conclusions: For elderly admitted to ICU after noncardiac surgery, low-dose dexmedetomidine infusion did not significantly change 3-year overall survival, but increased survival up to 2 years, and improved cognitive function and quality of life in 3-year survivors.

Xenon possesses some, but not all, of the clinical features of an ideal anesthetic agent. Besides well-known advantages of rapid awakening, stable hemodynamics and lack of biotransformation, preclinical data lead to the expectation of xenon's advantageous use for settings of acute ongoing brain injury; a single randomized clinical trial using an imaging biomarker for assessing brain injury corroborated xenon's preclinical efficacy in protecting the brain from further injury. In this review, we discuss the mechanisms and hence the putative applications of xenon for brain protection in neurosurgery. Although the expense of this rare monoatomic gas will likely prevent its widespread penetration into routine clinical neurosurgical practice, we draw attention to the theoretical benefits of xenon anesthesia over other anesthetic regimens for awake craniotomy and for neurosurgery in older, high-risk, and sicker patients.

As part of the American Society of Anesthesiology Brain Health Initiative goal of improving perioperative brain health for older patients, over 30 experts met at the fifth International Perioperative Neurotoxicity Workshop in San Francisco, CA, in May 2016, to discuss best practices for optimizing perioperative brain health in older adults (ie, >65 years of age). The objective of this workshop was to discuss and develop consensus solutions to improve patient management and outcomes and to discuss what older adults should be told (and by whom) about postoperative brain health risks. Thus, the workshop was provider and patient oriented as well as solution focused rather than etiology focused. For those areas in which we determined that there were limited evidence-based recommendations, we identified knowledge gaps and the types of scientific knowledge and investigations needed to direct future best practice. Because concerns about perioperative neurocognitive injury in pediatric patients are already being addressed by the SmartTots initiative, our workshop discussion (and thus this article) focuses specifically on perioperative cognition in older adults. The 2 main perioperative cognitive disorders that have been studied to date are postoperative delirium and cognitive dysfunction. Postoperative delirium is a syndrome of fluctuating changes in attention and level of consciousness that occurs in 20%-40% of patients >60 years of age after major surgery and inpatient hospitalization. Many older surgical patients also develop postoperative cognitive deficits that typically last for weeks to months, thus referred to as postoperative cognitive dysfunction. Because of the heterogeneity of different tools and thresholds used to assess and define these disorders at varying points in time after anesthesia and surgery, a recent article has proposed a new recommended nomenclature for these perioperative neurocognitive disorders. Our discussion about this topic was organized around 4 key issues: preprocedure consent, preoperative cognitive assessment, intraoperative management, and postoperative follow-up. These 4 issues also form the structure of this document. Multiple viewpoints were presented by participants and discussed at this in-person meeting, and the overall group consensus from these discussions was then drafted by a smaller writing group (the 6 primary authors of this article) into this manuscript. Of course, further studies have appeared since the workshop, which the writing group has incorporated where appropriate. All participants from this in-person meeting then had the opportunity to review, edit, and approve this final manuscript; 1 participant did not approve the final manuscript and asked for his/her name to be removed.

Background: Inflammation initiated by damage-associated molecular patterns has been implicated for the cognitive decline associated with surgical trauma and serious illness. We determined whether resolution of inflammation mediates dexmedetomidine-induced reduction of damage-associated molecular pattern-induced cognitive decline., Methods: Cognitive decline (assessed by trace fear conditioning) was induced with high molecular group box 1 protein, a damage-associated molecular pattern, in mice that also received blockers of neural (vagal) and humoral inflammation-resolving pathways. Systemic and neuroinflammation was assessed by proinflammatory cytokines., Results: Damage-associated molecular pattern-induced cognitive decline and inflammation (mean ± SD) was reversed by dexmedetomidine (trace fear conditioning: 58.77 ± 8.69% vs. 41.45 ± 7.64%, P < 0.0001; plasma interleukin [IL]-1β: 7.0 ± 2.2 pg/ml vs. 49.8 ± 6.0 pg/ml, P < 0.0001; plasma IL-6: 3.2 ± 1.6 pg/ml vs. 19.5 ± 1.7 pg/ml, P < 0.0001; hippocampal IL-1β: 4.1 ± 3.0 pg/mg vs. 41.6 ± 8.0 pg/mg, P < 0.0001; hippocampal IL-6: 3.4 ± 1.3 pg/mg vs. 16.2 ± 2.7 pg/mg, P < 0.0001). Reversal by dexmedetomidine was prevented by blockade of vagomimetic imidazoline and α7 nicotinic acetylcholine receptors but not by α2 adrenoceptor blockade. Netrin-1, the orchestrator of inflammation-resolution, was upregulated (fold-change) by dexmedetomidine (lung: 1.5 ± 0.1 vs. 0.7 ± 0.1, P < 0.0001; spleen: 1.5 ± 0.2 vs. 0.6 ± 0.2, P < 0.0001), resulting in upregulation of proresolving (lipoxin-A4: 1.7 ± 0.2 vs. 0.9 ± 0.2, P < 0.0001) and downregulation of proinflammatory (leukotriene-B4: 1.0 ± 0.2 vs. 3.0 ± 0.3, P < 0.0001) humoral mediators that was prevented by α7 nicotinic acetylcholine receptor blockade., Conclusions: Dexmedetomidine resolves inflammation through vagomimetic (neural) and humoral pathways, thereby preventing damage-associated molecular pattern-mediated cognitive decline.

Background: Sleep is integral to biologic function, and sleep disruption can result in both physiological and psychologic dysfunction including cognitive decline. Surgery activates the innate immune system, inducing neuroinflammatory changes that interfere with cognition. Because surgical patients with sleep disorders have an increased likelihood of exhibiting postoperative delirium, an acute form of cognitive decline, we investigated the contribution of perioperative sleep fragmentation (SF) to the neuroinflammatory and cognitive responses of surgery., Methods: The effects of 24-hour SF and surgery were explored in adult C57BL/6J male mice. The SF procedure started at 7 AM with cages being placed on a large platform orbital shaker that cycled every 120 seconds (30 seconds on/90 seconds off) for 24 hours. In separate cohorts, stabilized tibial fracture was performed either before or after the 24-hour SF procedure and assessed for systemic and hippocampal inflammation and cognition., Results: SF-induced nonhippocampal memory dysfunction (mean ± standard deviation [SD] of the difference in time spent between novel and familiar object for control was 4.7 ± 1.4 seconds, n = 8 versus SF -0.5 ± 0.2 seconds, n = 11, yielding an estimated treatment effect of 5.2 seconds [95% confidence interval {CI}, 2.6-7.7]; P < .001) and increased systemic interleukin-6 (median [25%-75% quartile] for control 0.0 [0.0-2.4] pg/mL versus 9.7 [6.3-12.9] pg/mL, n = 8/group, yielding an estimated treatment effect of 9.7 pg/mL [95% CI, 5.8-11.8]; P < .0001). SF reduced freezing time in hippocampal-dependent memory test (mean ± SD for control 49.3% ± 5.8% versus for SF 32.9% ± 5.8%, n = 10/group, estimated treatment effect = 16.4% [95% CI, 11.0-21.8]; P < .0001). Although surgery also reduced freezing time (mean ± SD for control 49.3% ± 5.8% versus for surgery 30.3% ± 3.3%, n = 10/group, estimated treatment effect = 19.0% [95% CI, 14.6-23.4]; P < .0001), memory impairment was not further exacerbated by combining SF with surgery. One day after SF, there was an increase in hippocampal messenger RNA expression of tumor necrosis factor-α (relative quantitation [RQ] 5.12-fold, n = 5/group [95% CI, 1.64-15.97]; P < .01), and 1 day after surgery, there was an increase in messenger RNA interleukin-6 (RQ 4.64-fold, n = 5 [95% CI, 1.48-14.56]; P < .05) and tumor necrosis factor-α (RQ 5.54-fold, n = 5 [95% CI, 2.92-10.51]; P < .01). These increments were more pronounced when either pre- or postoperative SF was combined with surgery., Conclusions: Although SF and surgery can independently produce significant memory impairment, perioperative SF significantly increased hippocampal inflammation without further cognitive impairment. The dissociation between neuroinflammation and cognitive decline may relate to the use of a sole memory paradigm that does not capture other aspects of cognition, especially learning.

Dexmedetomidine Diminishes Halothane Anesthetic Requirements in Rats Through a Postsynaptic Alpha 2 Adrenergic Receptor. By Segal IS, Vickery RG, Walton JK, Doze VA, and Maze M. ANESTHESIOLOGY 1988; 125:590-4. Abstract reprinted with permission.The effect of 4(5)-[1-(2,3-dimethylphenyl)ethyl]imidazole (medetomidine), the α2 adrenergic agonist, on anesthetic requirements was investigated in rats anesthetized with halothane. Halothane MAC was determined before and after either dexmedetomidine (D-enantiomer) or levomedetomidine (L-enantiomer) 10, 30, and 100 μg/kg, or vehicle intraperitoneally. There was a dose-dependent increase in MAC with the D-, but not the L-, stereoisomer. At the highest dose of dexmedetomidine (100 μg/kg), halothane could be discontinued for up to 30 min with no response to tail clamping. To determine whether α2 adrenoreceptors mediated this effect of dexmedetomidine on MAC, cohorts of rats were pretreated with idazoxan, 10 mg/kg intraperitoneally, a highly selective α2 antagonist. This completely prevented the reduction of MAC caused by dexmedetomidine. To determine whether the reduction of MAC caused by dexmedetomidine was mediated in part through either opiate or adenosine receptors, groups of rats were pretreated with either naltrexone, 5 mg/kg intraperitoneally, an opiate antagonist, or 8-phenyltheophylline, 2.5 mg/kg intraperitoneally, an A1 adenosine antagonist. These two pretreatments did not alter the reduction of MAC by dexmedetomidine. To determine whether postsynaptic mechanisms mediate the anesthetic effect of dexmedetomidine, rats were depleted of central catecholamine stores with either n-(2-chloroethyl)-n-ethyl-2-bromobenzylamine or reserpine and α-methyl-para-tyrosine, and MAC was determined before and after each dose of dexmedetomidine. While the catecholamine-depleted rats had a lower basal MAC than the vehicle controls, there was still a profound reduction in halothane MAC after administration of dexmedetomidine. The reduction of MAC by dexmedetomidine was blocked with idazoxan in the catecholamine-depleted rats. These data indicate that the reduction of MAC caused by dexmedetomidine is mediated through α2 adrenoreceptors with no apparent involvement of either opiate or A1 adenosine receptors. Data from catecholamine-depleted rats suggest that the mediating mechanism must involve site(s) other than or in addition to the presynaptic α2 adrenergic receptors on noradrenergic neurons. The authors conclude that central postsynaptic α2 adrenergic receptors mediate a significant part of the reduction of anesthetic requirements caused by dexmedetomidine.

Background: Sleep disruption in critically ill adults can result in acute decrements in cognitive function, including delirium, but it is underdiagnosed in the setting of the intensive care unit (ICU). Although sleep stages can be assessed by polysomnography (PSG), acquisition and interpretation of PSG is costly, is labor intensive, is difficult to do over an extended period of time with critically ill patients (multiple days of continuous recording), and may interfere with patient care. In this pilot study, we investigated the feasibility and utility of monitoring sleep in the ICU setting using a portable electroencephalography (EEG) monitor, the SedLine brain monitor., Methods: We first performed a baseline comparison study of the SedLine brain monitor by comparing its recordings to PSG recorded in a sleep laboratory (n = 3). In a separate patient cohort, we enrolled patients in the ICU who were monitored continuously with the SedLine monitor for sleep disruption (n = 23). In all enrolled patients, we continuously monitored their EEG. The raw EEG was retrieved and sleep stages and arousals were analyzed by a board-certified technologist. Delirium was measured by a trained research nurse using the Confusion Assessment Method developed for the ICU., Results: For all enrolled patients, we continuously monitored their EEGs and were able to retrieve the raw EEGs for analysis of sleep stages. Overall, the SedLine brain monitor was able to differentiate sleep stages, as well as capture arousals and transitions between sleep stages compared with the PSG performed in the sleep laboratory. The percentage agreement was 67% for the wake stage, 77% for the non-rapid eye movement (REM) stage (N1 = 29%, N2 = 88%, and N3 = 6%), and 89% for the REM stage. The overall agreement was measured with the use of weighted kappa, which was 0.61, 95% confidence interval, 0.58 to 0.64. In the ICU study, the mean recording time for the 23 enrolled patients was 19.10 hours. There were several signs indicative of poor-quality sleep, where sleep was distributed throughout the day, with reduced time spent in REM (1.38% ± 2.74% of total sleep time), and stage N3 (2.17% ± 5.53% of total sleep time) coupled with a high arousal index (34.63 ± 19.04 arousals per hour). The occurrence of ICU delirium was not significantly different between patients with and without sleep disruption., Conclusions: Our results suggest the utility of a portable EEG monitor to measure different sleep stages, transitions, and arousals; however, the accuracy in measuring different sleep stages by the SedLine monitor varies compared with PSG. Our results also support previous findings that sleep is fragmented in critically ill patients. Further research is necessary to develop portable EEG monitors that have higher agreement with PSG.