Anesthesia may induce neurotoxicity and neurocognitive impairment in young mice. However, the underlying mechanism remains largely to be determined. Meanwhile, autophagy is involved in brain ...development and contributes to neurodegenerative diseases. We, therefore, set out to determine the effects of sevoflurane on autophagy in the hippocampus of young mice and on cognitive function in the mice.
Six day-old mice received 3% sevoflurane, for two hours daily, on postnatal days (P) 6, 7 and 8. We then decapitated the mice and harvested the hippocampus of the young mice at P8. The level of LC3, the ratio of LC3-II to LC3-I, and SQSTM1/p62 level associated with the autophagy in the hippocampus of the mice were assessed by using Western blotting. We used different groups of mice for behavioral testing via the Morris Water Maze from P31 to P37.
The anesthetic sevoflurane increased the level of LC3-II and ratio of LC3-II/LC3-I, decreased the p62 level in the hippocampus of the young mice, and induced cognitive impairment in the mice. 3-Methyladenine, the inhibitor of autophagy, attenuated the activation of autophagy and ameliorated the cognitive impairment induced by sevoflurane in the young mice.
These data showed that sevoflurane anesthesia might induce cognitive impairment in the young mice via activation of autophagy in the hippocampus of the young mice. These findings from the proof of concept studies have established a system and suggest the role of autophagy in anesthesia neurotoxicity and cognitive impairment in the young mice, pending further investigation.
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BACKGROUND:Postoperative pain management remains a significant challenge after abdominal surgery.
OBJECTIVE:The aim of this meta-analysis was to evaluate the efficacy of systemic lidocaine for ...postoperative pain management and recovery after abdominal surgery.
DATA SOURCE:Data were derived from Medline (1966–2010), CINAHL, The Cochrane Central Register of Controlled Trials, and Scopus.
STUDY SELECTION:Randomized controlled trials of systemic administration of lidocaine for postoperative analgesia and recovery after abdominal surgery in adults, ie, >18 years, were considered.
INTERVENTIONS:Combined data were analyzed with use of a random-effects model.
MAIN OUTCOMES MEASURES:Data on opioid consumption, postoperative pain intensity, opioid-related side effects, time to first flatus, time to first bowel movement, and length of hospital stay were extracted.
RESULTS:Twenty-one trials comparing systemic lidocaine with placebo or blank control for postoperative analgesia and recovery after abdominal surgery were included in this meta-analysis. Weighted mean difference for cumulative analgesic opioid (morphine) consumption 48 hours after surgery was –7.04 mg (95% CI–10.40, –3.68, I = 46.1%).Systemic lidocaine also significantly reduced postoperative pain intensity(visual analog scale, 0–100 mm) 6 hours after surgery at rest (weighted mean difference–8.07 mm (95% CI–14.69, –1.49); I = 90.6%) and during activity (weighted mean difference–10.56 mm (95% CI–16.89, –4.23), I = 82%). The time to first flatus and bowel movement was significantly shortened with lidocaine intervention by 6.92 hours (95% CI–9.21, –4.63, I = 62.8%) and 11.74 hours (95% CI:–16.97, –6.51, I = 0). Moreover, systemic lidocaine also reduced hospital length of stay following the open procedure (weighted mean difference–0.71 days (95% CI–1.35, –0.07); I = 37.3%).
LIMITATIONS:Heterogeneity of study results is the main limitation of this meta-analysis.
CONCLUSION:Perioperative systemic lidocaine may be a useful adjunct for postoperative pain management by decreasing postoperative pain intensity, reducing opioid consumption, facilitating GI function, and shortening length of hospital stay.
Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment choice for peritoneal cancer. However, patients commonly suffer from severe postoperative ...pain. The pathophysiology of postoperative pain is considered to be from both nociceptive and neuropathic origins.
The recent advances on the etiology of postoperative pain after CRS + HIPEC treatment were described, and the treatment strategy and outcomes were summarized.
Conventional analgesics could provide short-term symptomatic relief. Thoracic epidural analgesia combined with opioids administration could be an effective treatment choice. In addition, a transversus abdominis plane block could also be an alternative option, although further studies should be performed.
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Sedation induces changes in electroencephalography (EEG) dynamics. However, the distinct EEG dynamic characteristics at comparable sedation levels have not been well studied, resulting in potential ...interpretation errors in EEG monitoring during sedation. We aimed to analyze the EEG dynamics of dexmedetomidine and propofol at comparable sedation levels and to explore EEG changes with increased sedation levels for each agent. We measured the Bispectral Index (BIS) and 20-channel EEG under dexmedetomidine and propofol sedation from wakefulness, moderate sedation, and deep sedation to recovery in healthy volunteers (n = 10) in a randomized, 2-day, crossover study. Observer's Assessment of Alertness and Sedation (OAA/S) score was used to assess sedation levels. Despite similar changes in increased delta oscillations, multiple differences in the EEG spatiotemporal dynamics were observed between these two agents. During moderate sedation, both dexmedetomidine and propofol induced increased spindle power; however, dexmedetomidine decreased the global alpha/beta/gamma power, whereas propofol decreased the alpha power in the occipital area and increased the global spindle/beta/gamma power. During deep sedation, dexmedetomidine was associated with increased fronto-central spindle power and decreased global alpha/beta/gamma power, but propofol was associated with increased theta/alpha/spindle/beta power, which was maximized in the frontal area. The transition of topographic alpha/spindle/beta power distribution from moderate sedation to deep sedation completely differed between these two agents. Our study demonstrated that there was a distinct hierarchy of EEG changes with increased sedation depths by propofol and dexmedetomidine. Differences in EEG dynamics at the same sedation level might account for differences in the BIS value and reflect the different sedation mechanisms. EEG-based clinical sedation monitoring should consider the effect of drug types on EEG dynamics.
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To explore the influences of total intravenous anesthesia (TIVA) and inhaled-intravenous anesthesia on the prognosis of patients with lung, breast, or esophageal cancer.
In this retrospective cohort ...study, patients with lung, breast, or esophageal cancer who underwent surgical treatments at Beijing Shijitan Hospital between January 2010 and December 2019 were included. The patients were categorized into the TIVA group and inhaled-intravenous anesthesia group, according to the anesthesia methods used for the patients for surgery of the primary cancer. The primary outcome of this study included overall survival (OS) and recurrence/metastasis.
Totally, 336 patients were included in this study, 119 in the TIVA group and 217 in the inhaled-intravenous anesthesia group. The OS of patients in the TIVA group was higher than in the inhaled-intravenous anesthesia group (
= 0.042). There were no significant differences in the recurrence/metastasis-free survival between the two groups (
= 0.296). Inhaled-intravenous anesthesia (HR = 1.88, 95%CI: 1.15-3.07,
= 0.012), stage III cancer (HR = 5.88, 95%CI: 2.57-13.43,
< 0.001), and stage IV cancer (HR = 22.60, 95%CI: 8.97-56.95,
< 0.001) were independently associated with recurrence/ metastasis. Comorbidities (HR = 1.75, 95%CI: 1.05-2.92,
= 0.033), the use of ephedrine, noradrenaline or phenylephrine during surgery (HR = 2.12, 95%CI: 1.11-4.06,
= 0.024), stage II cancer (HR = 3.24, 95%CI: 1.08-9.68,
= 0.035), stage III cancer (HR = 7.60, 95%CI: 2.64-21.86,
< 0.001), and stage IV cancer (HR = 26.61, 95%CI: 8.57-82.64,
< 0.001) were independently associated with OS.
In patients with breast, lung, or esophageal cancer, TIVA is preferable than inhaled-intravenous anesthesia group for longer OS,, but TIVA was not associated with the recurrence/metastasis-free survival of patients.
Postoperative cognitive dysfunction (POCD) is a disturbing neurological complication in patients undergoing anesthesia and surgical procedures. Brain-derived neurotrophic factor (BDNF) and its ...precursor proBDNF binding to their corresponding receptors tyrosine kinase (TrkB) and p75 neurotrophin receptor (p75NTR) exert quite an opposite biological function in neuron survival and synaptic function. This study aimed to demonstrate the critical role of the BDNF/proBDNF ratio in modulating synaptic plasticity, which further leads to anesthesia-/surgery-induced POCD. It also showed that the exogenous BDNF or p75NTR inhibitor could ameliorate cognitive dysfunction. In detail, 16-month-old C57BL/6 mice were subjected to a stabilized tibial fracture surgery with isoflurane anesthesia to establish the POCD animal model. The mice were then microinjected with either p75NTR inhibitor or exogenous BDNF into the dorsal hippocampus. Behavioral experiments were performed by open field and fear conditioning tests (FCTs). Western blotting was also used to measure the expression levels of BDNF, proBDNF, TrkB, p-TrkB, p75NTR, and synapse proteins. Golgi staining and electrophysiology were applied to evaluate the neuronal synaptic plasticity. Here, we demonstrated that anesthesia/surgery induced a reduction of BDNF/proBDNF, which negatively regulates the synaptic function in hippocampus, subsequently leading to cognitive impairment in aged mice. P75NTR inhibitor and exogenous BDNF could attenuate cognitive deficits by rescuing the dendritic spine loss and long-term potentiation (LTP)
altering the BDNF/proBDNF ratio. This study unveiled that the BDNF/proBDNF ratio in the hippocampus played a key role in anesthesia-/surgery-induced POCD. Thereby, tuning the ratio of BDNF/proBDNF is supposed to be a promising therapeutic target for POCD.
Postoperative cognitive dysfunction (POCD) is a common brain function-related complication after surgery. In addition to old age being an independent risk factor, anesthetics are also important ...predisposing factors. Among them, propofol is the most commonly used intravenous anesthetic in clinical practice. It has a rapid onset, short half-life, and high recovery quality. Many studies report that propofol can attenuate surgery-induced cognitive impairment, however, some other studies reveal that propofol also induces cognitive dysfunction. Therefore, this review summarizes the effects of propofol on the cognition, and discusses possible related mechanisms, which aims to provide some evidence for the follow-up studies.
Inadvertent intraoperative hypothermia (core temperature <360 C) is a recognized risk in surgery and has adverse consequences. However, no data about this complication in China are available. Our ...study aimed to determine the incidence of inadvertent intraoperative hypothermia and its associated risk factors in a sample of Chinese patients.
We conducted a regional cross-sectional survey in Beijing from August through December, 2013. Eight hundred thirty patients who underwent various operations under general anesthesia were randomly selected from 24 hospitals through a multistage probability sampling. Multivariate logistic regression analyses were applied to explore the risk factors of developing hypothermia.
The overall incidence of intraoperative hypothermia was high, 39.9%. All patients were warmed passively with surgical sheets or cotton blankets, whereas only 10.7% of patients received active warming with space heaters or electric blankets. Pre-warmed intravenous fluid were administered to 16.9% of patients, and 34.6% of patients had irrigation of wounds with pre-warmed fluid. Active warming (OR = 0.46, 95% CI 0.26-0.81), overweight or obesity (OR = 0.39, 95% CI 0.28-0.56), high baseline core temperature before anesthesia (OR = 0.08, 95% CI 0.04-0.13), and high ambient temperature (OR = 0.89, 95% CI 0.79-0.98) were significant protective factors for hypothermia. In contrast, major-plus operations (OR = 2.00, 95% CI 1.32-3.04), duration of anesthesia (1-2 h) (OR = 3.23, 95% CI 2.19-4.78) and >2 h (OR = 3.44, 95% CI 1.90-6.22,), and intravenous un-warmed fluid (OR = 2.45, 95% CI 1.45-4.12) significantly increased the risk of hypothermia.
The incidence of inadvertent intraoperative hypothermia in Beijing is high, and the rate of active warming of patients during operation is low. Concern for the development of intraoperative hypothermia should be especially high in patients undergoing major operations, requiring long periods of anesthesia, and receiving un-warmed intravenous fluids.
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The mechanism of general anesthesia (GA) has been explored for hundreds of years, but unclear. Previous studies indicated a possible correlation between NREM sleep and GA. The purpose of this study ...is to compare them by in vivo human brain function to probe the neuromechanism of consciousness, so as to find out a clue to GA mechanism.
24 healthy participants were equally assigned to sleep or propofol sedation group by sleeping ability. EEG and Ramsay Sedation Scale were applied to determine sleep stage and sedation depth respectively. Resting-state functional magnetic resonance imaging (RS-fMRI) was acquired at each status. Regional homogeneity (ReHo) and seed-based whole brain functional connectivity maps (WB-FC maps) were compared.
During sleep, ReHo primarily weakened on frontal lobe (especially preoptic area), but strengthened on brainstem. While during sedation, ReHo changed in various brain areas, including cingulate, precuneus, thalamus and cerebellum. Cingulate, fusiform and insula were concomitance of sleep and sedation. Comparing to sleep, FCs between the cortex and subcortical centers (centralized in cerebellum) were significantly attenuated under sedation. As sedation deepening, cerebellum-based FC maps were diminished, while thalamus- and brainstem-based FC maps were increased.
There're huge distinctions in human brain function between sleep and GA. Sleep mainly rely on brainstem and frontal lobe function, while sedation is prone to affect widespread functional network. The most significant differences exist in the precuneus and cingulate, which may play important roles in mechanisms of inducing unconciousness by anesthetics.
Institutional Review Board (IRB) ChiCTR-IOC-15007454.
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Background
Postoperative delirium (POD) is a common aging-associated postoperative complication that has received increasing attention in the context of the aging global population and the number of ...articles published on POD is gradually increasing. This study aimed to quantify the basic information of scholarly publications on POD and identify the most impactful literature, trends, and hotspots in POD research.
Materials and methods
We searched articles on POD through the Science Citation Index Expanded databases published from 2000 to 2020. Bibliographic information, including year, country, authorship, type, journal, funding, affiliations, subject areas, and hotspots, was collected for further analysis.
Results
A total of 2,114 articles on POD from 2000 to 2020 were identified. The highest number of studies (
n
= 748) were published in the United States, comprising the most total citations (13,928), followed by China (
n
= 278), and Germany (
n
= 209). Inouye, Sharon K. was the most productive author, with 66 publications on POD. The
Journal of the American Geriatrics Society
published the highest number of articles (
n
= 80), with the most total citations (4,561) and average (57.01), followed by
Anesthesia and Analgesia
(
n
= 52), and the
British Journal of Anaesthesia
(
n
= 43). Harvard University was the most productive institute, with the highest H-index (
n
= 46) and highest degree centrality (
n
= 191). The top hotspots in the field of POD during this period were “elderly,” “cardiac surgery,” “cognitive impairment,” “hip fracture,” and “intensive care unit.”
Conclusion
This study provides an overview of developments in the field of POD over the past 20 years using bibliometric analysis. Overall, research on POD has flourished worldwide. The United States (US) has a relatively high academic impact owing to its productive expertise and institutions in this field. Despite much research illustrating the diagnosis and management of POD in clinical practice, more basic research is needed.
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