Recovery of consciousness and cognition after general anesthesia in humans.
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ABSTRACT:
SUBMITTER: Mashour GA
PROVIDER: S-EPMC8163502 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Recent data from our laboratory demonstrate that high-frequency gamma connectivity across the cortex is present during consciousness and depressed during unconsciousness. However, these data were derived from static and well-defined states of arousal rather than during transitions that would suggest functional relevance. We also recently found that subanesthetic ketamine administered during isoflurane anesthesia accelerates recovery upon discontinuation of the primary anesthetic and increases gamma power during emergence. In the current study we re-analyzed electroencephalogram (EEG) data to test the hypothesis that functional cortical connectivity between anterior and posterior cortical regions would be increased during accelerated recovery induced by ketamine when compared to saline-treated controls. Rodents were instrumented with intracranial EEG electrodes and general anesthesia was induced with isoflurane anesthesia. After 37.5 min of continuous isoflurane anesthesia, a subanesthetic dose of ketamine (25 mg/kg intraperitoneal) was administered, with evidence of a 44% reduction in emergence time. In this study, we analyzed gamma and theta coherence (measure of undirected functional connectivity) and normalized symbolic transfer entropy (measure of directed functional connectivity) between frontal and parietal cortices during various levels of consciousness, with a focus on emergence from isoflurane anesthesia. During accelerated emergence in the ketamine-treated group, there was increased frontal-parietal coherence {p = 0.005, 0.05-0.23 [95% confidence interval (CI)]} and normalized symbolic transfer entropy [frontal to parietal: p < 0.001, 0.010-0.026 (95% CI); parietal to frontal: p < 0.001, 0.009-0.025 (95% CI)] in high-frequency gamma bandwidth as compared with the saline-treated group. Surrogates of cortical information exchange in high-frequency gamma are increased in association with accelerated recovery from anesthesia. This finding adds evidence suggesting a functional significance of high-gamma information transfer in consciousness.
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Project description:Previous studies have proved that astrocytes may be a key neural substrate that regulates wakefulness and consciousness recovery from general anesthesia, while the exact molecular target in astrocytes is still unclear. Using virus injection and in vivo fiber photometry in mice, we found both activating astrocytes and knocking down astrocytic Kir4.1 in paraventricular thalamus (PVT) promotes the consciousness recovery from sevoflurane anesthesia. Single-cell RNA sequencing of PVT reveals two distinct cellular subtypes of glutamatergic neurons: PVTGRM and PVTChAT neurons. Patch-clamp recording results proved that Astrocytic Kir4.1-mediated modulation of sevoflurane on PVT mainly works on PVTChAT neurons. Moreover, we found that PVTChAT neurons project mainly to the mPFC. This specific paraventricular thalamus to prefrontal cortex projection is involved in recovery of consciousness from sevoflurane anesthesia indirectly through modulation of astrocytes. In summary, our findings support the novel conception that the volatile anesthetic sevoflurane can inhibit PVT astrocytic Kir 4.1 to maintain and/or increase neuronal firing of PVTChAT neurons, which mainly projects to mPFC and promotes consciousness recovery from anesthesia.
2024-07-20 | GSE240388 | GEO
Project description:Neurons communicate with each other dynamically; how such communications lead to consciousness remains unclear. Here, we present a theoretical model to understand the dynamic nature of sensory activity and information integration in a hierarchical network, in which edges are stochastically defined by a single parameter p representing the percolation probability of information transmission. We validate the model by comparing the transmitted and original signal distributions, and we show that a basic version of this model can reproduce key spectral features clinically observed in electroencephalographic recordings of transitions from conscious to unconscious brain activities during general anesthesia. As p decreases, a steep divergence of the transmitted signal from the original was observed, along with a loss of signal synchrony and a sharp increase in information entropy in a critical manner; this resembles the precipitous loss of consciousness during anesthesia. The model offers mechanistic insights into the emergence of information integration from a stochastic process, laying the foundation for understanding the origin of cognition.
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Project description:BackgroundCircadian rhythm involved with physiology has been reported to affect pharmacokinetics or pharmacodynamics. We hypothesized that circadian variations in physiology disturb anesthesia and eventually affect recovery after anesthesia.MethodsA retrospective cohort study initially included 107,406 patients (1 June 2016-6 June 2021). Patients were classified into morning or afternoon surgery groups. The primary outcome was daytime variation in PACU (post-anesthesia care unit) recovery time and Steward score. Inverse probability weighting (IPW) approach based on propensity score and univariable/multivariable linear regression were used to estimate this outcome.ResultsOf 28,074 patients, 13,418 (48%) patients underwent morning surgeries, and 14,656 (52%) patients underwent afternoon surgeries. LOWESS curves and IPW illustrated daytime variation in PACU recovery time and Steward score. Before adjustment, compared to morning surgery group, afternoon surgery group had less PACU recovery time (median [interquartile range], 57 [46, 70] vs. 54 [43, 66], p < 0.001) and a higher Steward score (5.62 [5.61, 5.63] vs. 5.66 [5.65, 5.67], p < 0.001). After adjustment, compared to morning surgery group, afternoon surgery group had less PACU recovery time (58 [46, 70] vs. 54 [43, 66], p < 0.001). In multivariable linear regression, morning surgery is statistically associated with an increased PACU recovery time (coefficient, -3.20; 95% confidence interval, -3.55 to -2.86).Among non-cardiac surgeries, daytime variation might affect recovery after general anesthesia. These findings indicate that the timing of surgery improves recovery after general anesthesia, with afternoon surgery providing protection.KEY MESSAGESIn this retrospective cohort study of 28,074 participants, the afternoon surgery group has a higher Steward score than the morning surgery group.In multivariable linear regression, morning surgery is statistically associated with an increased PACU recovery time.Among non-cardiac surgeries, daytime variation affects the recovery after general anesthesia, with afternoon surgery providing protection.
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Project description:Sleep disorder dramatically affects people's physical and mental health. Here, we investigated the effect of preoperative sleep disorders on anesthesia recovery and postoperative pain in patients undergoing laparoscopic gynecological surgery under general anesthesia. 120 patients who underwent elective laparoscopic gynecological surgery under general anesthesia in Taizhou Central Hospital from November 2021 to March 2022 were included. According to the score of the Pittsburgh sleep quality index (PSQI), the participating patients were divided into four groups: control group (control group), mild sleep disorder group A (group A), moderate sleep disorder group B (group B), and severe sleep disorder group C (group C), with 30 patients in each group. The changes of mean arterial pressure (MAP) and heart rate (HR) at different time points, operation time, anesthesia time, extubation time, the time when Aldrete score reached 10 points, visual analog score (VAS) serum interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) were compared among different groups. Our study demonstrated that there were no significant differences in MAP and HR among the four groups at the same time points (all P > 0.05). Significant differences in the time of extubation and Aldrete score reaching 10 points had been found among the four groups (all P < 0.001), indicating more sleep disorder induced longer extubation and recovery time. There were significant differences in VAS scores among the four groups at both different and the same time points (all P < 0.001), suggesting more sleep disorders induced more pain in the sufferers. Serum IL-6 levels were significantly higher in the three sleep disorder groups than the control group at 6 h and 24 h after the operation (all P < 0.05), while group C has the highest IL-6 levels as compared to the other group (P = 0.09 and P < 0.001, respectively). At 6 h after operation, serum levels of TNF-α in group C were significantly higher than in the control group (P = 0.044), but no significant differences were found in the other two groups (all P > 0.05). Positive correlation with preoperative PSQI score has been found with the times of extubation, the time of Aldrete score reaching 10 points, the VAS at 1 h, 6 h, and 24 h after operation, the level of serum IL-6 at 1 day before operation and 6 h and 24 h after operation, and the TNF-α at 6 h and 24 h after operation (all P < 0.001). The present study showed that the degree of preoperative sleep disorders could affect the quality of postoperative awakening and pain of patients undergoing laparoscopic gynecological surgery under general anesthesia, which might be associated with the aggravation of inflammatory reactions in the body.
| S-EPMC9779992 | biostudies-literature
Project description:Neuronal stimulation improves physiological responses to infection and trauma, but the clinical potential of this strategy is unknown. We hypothesized that transdermal neural stimulation through low-frequency electroacupuncture might control the immune responses to surgical trauma and expedite the postoperative recovery. However, the efficiency of electroacupuncture is questioned due to the placebo effect. Here, electroacupuncture was performed on anesthetized patients to avoid any placebo. This is a prospective double-blinded pilot trial to determine whether intraoperative electroacupuncture on anesthetized patients improves postoperative recovery. Patients with electroacupuncture required 60% less postoperative analgesic, even they had pain scores similar to those in the control patients. Electroacupuncture prevented postoperative hyperglycemia and attenuated serum adrenocorticotropic hormone in the older and heavier group of patients. From an immunological perspective, electroacupuncture did not affect the protective immune responses to surgical trauma, including the induction of interleukin-6 and interleukin-10. The most significant immunological effect of electroacupuncture was enhancing transforming growth factor-?1 production during surgery in the older and lighter group of patients. These results suggest that intraoperative electroacupuncture on anesthetized patients can reduce postoperative use of analgesics and improve immune and stress responses to surgery.
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Project description:Postoperative sleep disturbance and fatigue following radical mastectomy were high risks for prolonged convalescence in patients with breast cancer. The present study was designed to observe the effect of intraoperative use of dexmedetomidine on postoperative sleep, fatigue and recovery following radical mastectomy under general anesthesia. Forty-seven patients were randomized into two groups that were maintained with propofol/remifentanil/Ringer's solution (Control group), or propofol/remifentanil/Dexmedetomidine (DEX group) for surgery under general anesthesia. During the first night following surgery, patients receiving dexmedetomine spent more time sleeping when compared with those form the Control group. During the first week following operation, when compared with the Control group, patients from the DEX group had a higher score of global 40-item recovery questionnaire on day 3 following operation, and lower 9-question fatigue severity scores on day 3 and day 7 following operation. In conclusion, intraoperative use of dexmedetomidine is sufficient to improve postoperative sleep disorder, promote postoperative recovery. The adverse effect of dexmedetomidine on sleep disturbance might be contributed to its recovery-promoting effect.
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Project description:Anesthesia in infancy impairs performance in recognition memory tasks in mammalian animals, but it is unknown if this occurs in humans. Successful recognition can be based on stimulus familiarity or recollection of event details. Several brain structures involved in recollection are affected by anesthesia-induced neurodegeneration in animals. Therefore, we hypothesized that anesthesia in infancy impairs recollection later in life in humans and rats. Twenty eight children ages 6-11 who had undergone a procedure requiring general anesthesia before age 1 were compared with 28 age- and gender-matched children who had not undergone anesthesia. Recollection and familiarity were assessed in an object recognition memory test using receiver operator characteristic analysis. In addition, IQ and Child Behavior Checklist scores were assessed. In parallel, thirty three 7-day-old rats were randomized to receive anesthesia or sham anesthesia. Over 10 months, recollection and familiarity were assessed using an odor recognition test. We found that anesthetized children had significantly lower recollection scores and were impaired at recollecting associative information compared with controls. Familiarity, IQ, and Child Behavior Checklist scores were not different between groups. In rats, anesthetized subjects had significantly lower recollection scores than controls while familiarity was unaffected. Rats that had undergone tissue injury during anesthesia had similar recollection indices as rats that had been anesthetized without tissue injury. These findings suggest that general anesthesia in infancy impairs recollection later in life in humans and rats. In rats, this effect is independent of underlying disease or tissue injury.
| S-EPMC4168665 | biostudies-literature
Project description:The analysis of the central and the autonomic nervous systems (CNS, ANS) activities during general anesthesia (GA) provides fundamental information for the study of neural processes that support alterations of the consciousness level. In the present pilot study, we analyzed EEG signals and the heart rate (HR) variability (HRV) in a sample of 11 patients undergoing spinal surgery to investigate their CNS and ANS activities during GA obtained with propofol administration. Data were analyzed during different stages of GA: baseline, the first period of anesthetic induction, the period before the loss of consciousness, the first period after propofol discontinuation, and the period before the recovery of consciousness (ROC). In EEG spectral analysis, we found a decrease in posterior alpha and beta power in all cortical areas observed, except the occipital ones, and an increase in delta power, mainly during the induction phase. In EEG connectivity analysis, we found a significant increase of local efficiency index in alpha and delta bands between baseline and loss of consciousness as well as between baseline and ROC in delta band only and a significant reduction of the characteristic path length in alpha band between the baseline and ROC. Moreover, connectivity results showed that in the alpha band there was mainly a progressive increase in the number and in the strength of incoming connections in the frontal region, while in the beta band the parietal region showed mainly a significant increase in the number and in the strength of outcoming connections values. The HRV analysis showed that the induction of anesthesia with propofol was associated with a progressive decrease in complexity and a consequent increase in the regularity indexes and that the anesthetic procedure determined bradycardia which was accompanied by an increase in cardiac sympathetic modulation and a decrease in cardiac parasympathetic modulation during the induction. Overall, the results of this pilot study showed as propofol-induced anesthesia caused modifications on EEG signal, leading to a "rebalance" between long and short-range cortical connections, and had a direct effect on the cardiac system. Our data suggest interesting perspectives for the interactions between the central and autonomic nervous systems for the modulation of the consciousness level.
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Project description:During awake consciousness, the brain intrinsically maintains a dynamical state in which it can coordinate complex responses to sensory input. How the brain reaches this state spontaneously is not known. General anesthesia provides a unique opportunity to examine how the human brain recovers its functional capabilities after profound unconsciousness. We used intracranial electrocorticography and scalp EEG in humans to track neural dynamics during emergence from propofol general anesthesia. We identify a distinct transient brain state that occurs immediately prior to recovery of behavioral responsiveness. This state is characterized by large, spatially distributed, slow sensory-evoked potentials that resemble the K-complexes that are hallmarks of stage two sleep. However, the ongoing spontaneous dynamics in this transitional state differ from sleep. These results identify an asymmetry in the neurophysiology of induction and emergence, as the emerging brain can enter a state with a sleep-like sensory blockade before regaining responsivity to arousing stimuli.
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