Preexisting factors such as age and cognitive performance can influence the electroencephalogram (EEG) during general anesthesia. Specifically, spectral EEG power is lower in elderly, compared to ...younger, subjects. Here, the authors investigate age-related changes in EEG architecture in patients undergoing general anesthesia through a detailed examination of spectral and entropic measures.
The authors retrospectively studied 180 frontal EEG recordings from patients undergoing general anesthesia, induced with propofol/fentanyl and maintained by sevoflurane at the Waikato Hospital in Hamilton, New Zealand. The authors calculated power spectral density and normalized power spectral density, the entropic measures approximate and permutation entropy, as well as the beta ratio and spectral entropy as exemplary parameters used in current monitoring systems from segments of EEG obtained before the onset of surgery (i.e., with no noxious stimulation).
The oldest quartile of patients had significantly lower 1/f characteristics (P < 0.001; area under the receiver operating characteristics curve, 0.84 0.76 0.92), indicative of a more uniform distribution of spectral power. Analysis of the normalized power spectral density revealed no significant impact of age on relative alpha (P = 0.693; area under the receiver operating characteristics curve, 0.52 0.41 0.63) and a significant but weak effect on relative beta power (P = 0.041; area under the receiver operating characteristics curve, 0.62 0.52 0.73). Using entropic parameters, the authors found a significant age-related change toward a more irregular and unpredictable EEG (permutation entropy: P < 0.001, area under the receiver operating characteristics curve, 0.81 0.71 0.90; approximate entropy: P < 0.001; area under the receiver operating characteristics curve, 0.76 0.66 0.85). With approximate entropy, the authors could also detect an age-induced change in alpha-band activity (P = 0.002; area under the receiver operating characteristics curve, 0.69 0.60 78).
Like the sleep literature, spectral and entropic EEG features under general anesthesia change with age revealing a shift toward a faster, more irregular, oscillatory composition of the EEG in older patients. Age-related changes in neurophysiological activity may underlie these findings however the contribution of age-related changes in filtering properties or the signal to noise ratio must also be considered. Regardless, most current EEG technology used to guide anesthetic management focus on spectral features, and improvements to these devices might involve integration of entropic features of the raw EEG.
General anesthetics have been used to ablate consciousness during surgery for more than 150 yr. Despite significant advances in our understanding of their molecular-level pharmacologic effects, ...comparatively little is known about how anesthetics alter brain dynamics to cause unconsciousness. Consequently, while anesthesia practice is now routine and safe, there are many vagaries that remain unexplained. In this paper, the authors review the evidence that cortical network activity is particularly sensitive to general anesthetics, and suggest that disruption to communication in, and/or among, cortical brain regions is a common mechanism of anesthesia that ultimately produces loss of consciousness. The authors review data from acute brain slices and organotypic cultures showing that anesthetics with differing molecular mechanisms of action share in common the ability to impair neurophysiologic communication. While many questions remain, together, ex vivo and in vivo investigations suggest that a unified understanding of both clinical anesthesia and the neural basis of consciousness is attainable.
Electroencephalographic (EEG) activity is used to monitor the neurophysiology of the brain, which is a target organ of general anaesthesia. Besides its use in evaluating hypnotic states, ...neurophysiologic reactions to noxious stimulation can also be observed in the EEG. Recognising and understanding these responses could help optimise intraoperative analgesic management. This review describes three types of changes in the EEG induced by noxious stimulation when the patient is under general anaesthesia: (1) beta arousal, (2) (paradoxical) delta arousal, and (3) alpha dropout. Beta arousal is an increase in EEG power in the beta-frequency band (12–25 Hz) in response to noxious stimulation, especially at lower doses of anaesthesia drugs in the absence of opioids. It is usually indicative of a cortical depolarisation and increased cortical activity. At higher concentrations of anaesthetic drug, and with insufficient opioids, delta arousal (increased power in the delta band 0.5–4 Hz) and alpha dropout (decreased alpha power 8–12 Hz) are associated with noxious stimuli. The mechanisms of delta arousal are not well understood, but the midbrain reticular formation seems to play a role. Alpha dropout may indicate a return of thalamocortical communication, from an idling mode to an operational mode. Each of these EEG changes reflect an incomplete modulation of pain signals and can be mitigated by administration of opioid or the use of regional anaesthesia techniques. Future studies should evaluate whether titrating analgesic drugs in response to these EEG signals reduces postoperative pain and influences other postoperative outcomes, including the potential development of chronic pain.
Recent interest in reversal of the hypnotic effects of anesthesia has mainly focused on overcoming a surge in GABA-mediated inhibitory signaling through activation of subcortical arousal circuits or ...antagonizing GABA receptors. Here we examine the reversal of anesthesia produced from non-GABA agents ketamine/xylazine and the effects of antagonists of adrenoreceptors. These antagonists vary in selectivity and produce temporally unique waking behavior post-anesthesia. We compared two antagonists with differential selectivity for α1- vs. α2-receptors, yohimbine (YOH, 1:40 selectivity) and atipamezole (ATI, 1:8500). Adult mice received intraperitoneal injections of either YOH (4.3 mg/kg), ATI (0.4 mg/kg), or saline after achieving sustained loss of righting following injection of ketamine/xylazine (ketamine: 65.0 mg/kg; xylazine: 9.9 mg/kg). Behaviors indicative of the post-anesthesia, re-animation sequence were carefully monitored and the timing of each behavior relative to anesthesia induction was compared. Both YOH and ATI hastened behaviors indicative of emergence, but ATI was faster than YOH to produce certain behaviors, including whisker movement (YOH: 21.9±1.5 min, ATI: 17.5±0.5 min, p = 0.004) and return of righting reflex (RORR) (YOH: 40.6±8.8 min, ATI: 26.0±1.2 min, p<0.001). Interestingly, although YOH administration hastened early behavioral markers of emergence relative to saline (whisking), the completion of the emergence sequence (time from first marker to appearance of RORR) was delayed with YOH. We attribute this effect to antagonism of α1 receptors by yohimbine. Also notable was the failure of either antagonist to hasten the re-establishment of coordinated motor behavior (e.g., attempts to remove adhesive tape on the forepaw placed during anesthesia) relative to the end of emergence (RORR). In total, our work suggests that in addition to pharmacokinetic effects, re-establishment of normal waking behaviors after anesthesia involves neuronal circuits dependent on time and/or activity.
Study objectivePostoperative neurocognitive disorders (PND) are common complications after surgery under general anesthesia. In our aging society the incidence of PND will increase. Hence, ...interdisciplinary efforts should be taken to minimize the occurrence of PND. Electroencephalographic (EEG) monitoring of brain activity during anesthesia or emergence from anesthesia is a promising tool to identify patients at risk. We therefore investigated whether we could identify specific EEG signatures during emergence of anesthesia that are associated with the occurrence of PND.Design and patientsWe performed a prospective observational investigation on 116 patients to evaluate the EEG features during emergence from general anesthesia dominated by slow delta waves in patients with and without delirium in the postoperative care unit (PACU-D) as assessed by the CAM-ICU and the RASS.Main resultsDuring emergence both the frontal and global EEG of patients with PACU-D were significantly different from patients without PACU-D. PACU-D patients had lower relative alpha power and reduced fronto-parietal alpha coherence.ConclusionsWith our analysis we show differences in EEG features associated with anesthesia emergence in patients with and without PACU-D. Frontal and global EEG alpha-band features could help to identify patients with PACU-D.Clinical trial number: NCT03287401
Despite accumulating evidence suggesting local self-maintenance of tissue macrophages in the steady state, the dogma remains that tissue macrophages derive from monocytes. Using parabiosis and ...fate-mapping approaches, we confirmed that monocytes do not show significant contribution to tissue macrophages in the steady state. Similarly, we found that after depletion of lung macrophages, the majority of repopulation occurred by stochastic cellular proliferation in situ in a macrophage colony-stimulating factor (M-Csf)- and granulocyte macrophage (GM)-CSF-dependent manner but independently of interleukin-4. We also found that after bone marrow transplantation, host macrophages retained the capacity to expand when the development of donor macrophages was compromised. Expansion of host macrophages was functional and prevented the development of alveolar proteinosis in mice transplanted with GM-Csf-receptor-deficient progenitors. Collectively, these results indicate that tissue-resident macrophages and circulating monocytes should be classified as mononuclear phagocyte lineages that are independently maintained in the steady state.
•Monocytes minimally contribute to tissue macrophages in the steady state•Monocytes minimally contribute to tissue macrophages after cell turnover•Tissue macrophage repopulation occurs locally and stochastically•Host tissue macrophages can functionally repopulate after genotoxic insult
The re-establishment of conscious awareness after discontinuing general anesthesia has often been assumed to be the inverse of loss of consciousness. This is despite the obvious asymmetry in the ...initiation and termination of natural sleep. In order to characterize the restoration of consciousness after surgery, we recorded frontal electroencephalograph (EEG) from 100 patients in the operating room during maintenance and emergence from general anesthesia. We have defined, for the first time, 4 steady-state patterns of anesthetic maintenance based on the relative EEG power in the slow-wave (<14 Hz) frequency bands that dominate sleep and anesthesia. Unlike single-drug experiments performed in healthy volunteers, we found that surgical patients exhibited greater electroencephalographic heterogeneity while re-establishing conscious awareness after drug discontinuation. Moreover, these emergence patterns could be broadly grouped according to the duration and rapidity of transitions amongst these slow-wave dominated brain states that precede awakening. Most patients progressed gradually from a pattern characterized by strong peaks of delta (0.5-4 Hz) and alpha/spindle (8-14 Hz) power ('Slow-Wave Anesthesia') to a state marked by low delta-spindle power ('Non Slow-Wave Anesthesia') before awakening. However, 31% of patients transitioned abruptly from Slow-Wave Anesthesia to waking; they were also more likely to express pain in the post-operative period. Our results, based on sleep-staging classification, provide the first systematized nomenclature for tracking brain states under general anesthesia from maintenance to emergence, and suggest that these transitions may correlate with post-operative outcomes such as pain.
The question of how general anesthetics suppress consciousness has persisted since the mid-19th century, but it is only relatively recently that the field has turned its focus to a systematic ...understanding of emergence. Once assumed to be a purely passive process, spontaneously occurring as residual levels of anesthetics dwindle below a critical value, emergence from general anesthesia has been reconsidered as an active and controllable process. Emergence is driven by mechanisms that can be distinct from entry to the anesthetized state. In this narrative review, we focus on the burgeoning scientific understanding of anesthetic emergence, summarizing current knowledge of the neurotransmitter, neuromodulators, and neuronal groups that prime the brain as it prepares for its journey back from oblivion. We also review evidence for possible strategies that may actively bias the brain back toward the wakeful state.
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